1 State Environmental Protection Key Laboratory of All Material Fluxes in River Ecosystems, The MOE Key Laboratory of Water and Sediment Sciences, College of Environmental Sciences and Engineering, Peking University,Beijing 100871, China
2 College of Environmental Science and Engineering, North China Electric Power University,Beijing 102206, China
3 School of Environmental Science and Engineering, Huazhong University of Science and Technology,Wuhan 430074, China
The novel coronavirus pneumonia epidemic (COVID-19) brings a serious threat to the development of human society and the health of human beings. Due to the stability of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in urban sewage, which has become one of the virus pollution sources, it has been a focus how to eliminate the existing virus in water. SARS-CoV-2 structurally consists of RNA chains and protein capsids, and thus can be inactivated via reactive oxygen species (ROS) attack. Moreover, block of biochemical metabolism and destruction of virus structure are also effective inactivation methods for SARS-CoV-2 inactivation. Nanomaterials exhibit surface and interface effects, specific microstructure and excellent physicochemical properties, implying their high application potential in SARS-CoV-2 inactivation. In this study, we overall review application of nanotechnologies for SARS-CoV-2 inactivation, including photocatalysis, heterogeneous catalytic oxidation, ion toxicity induced inactivation, and structural effects inactivation method. Furthermore, based on the structural composition, as well as survival and transmission characteristics of SARS-CoV-2 in water environment, the application potential of various nanotechnologies for SARS-CoV-2 inactivation are deeply discussed. This study can provide a theoretical basis and practical reference for the application of nanotechnology for the SARS-CoV-2 inactivation and the secondary transmission interruption in water.
Contents
1 Introduction
2 SARS-CoV-2 and water disinfection techniques
2.1 Structure and composition of SARS-CoV-2
2.2 Survival and transmission characteristics of SARS-CoV-2 in water
2.3 Techniques for SARS-CoV-2 disinfection in water
2.4 Evaluation methods on SARS-CoV-2 inactivation
3 Application of nanotechnology on virus inactivation and its feasibility analysis on SARS-CoV-2 inactivation
3.1 Nanomaterials enhanced advanced oxidation technologies(AOTs)based on radical attack for virus inactivation
3.2 Disinfection technologies based on released ions from nanomaterials
3.3 Disinfection technologies based on structure effect of nanomaterials
Haodong Ji, Juanjuan Qi, Maosheng Zheng, Chenyuan Dang, Long Chen, Taobo Huang, Wen Liu.
Application of Nanotechnology for Virus Inactivation in Water:Implications for Transmission-Blocking of the Novel Coronavirus SARS-CoV-2.
Progress in Chemistry, 2022, 34(1): 207-226 DOI:10.7536/PC210205
At the end of 2019, there was a worldwide outbreak of novel coronavirus pneumonia (COVID-19). As of January 2022, more than 5.5 million deaths have been reported worldwide. This is a large-scale epidemic caused by coronavirus since the beginning of this century, which has caused huge losses to human society and economy and seriously threatened people's lives and health[1a].
The novel coronavirus (SARS-CoV-2) is mainly transmitted by air (respiratory droplets) and close contact in the population. In addition, there is a possibility of aerosol transmission when exposed to high concentrations of aerosols for a long time in a relatively closed environment[1⇓⇓⇓~5]. Live virus was also successfully isolated from the feces of COVID-19 infected persons, proving that the virus is also a possible intestinal pathogen, and its epidemic transmission has an important relationship with water and wastewater.For example, the detected load of novel coronavirus in wastewater from sewage treatment plants in areas with different epidemic spread degrees ranges from 0.02 copies/ml to 3000 copies/ml, and there is a risk of transmission through water vectors through drainage systems[6][6,7]. However, at present, people's understanding of the survival time, transmission path and secondary environmental risks of coronavirus in water is not deep enough, and it is urgent to explore and take effective inactivation and transmission blocking measures[1].
The novel coronavirus has no cellular structure and cannot reproduce itself independently. It needs to infect host cells (human or animal) to complete life characteristics such as heredity and replication. The novel coronavirus is composed of a single-stranded ribonucleic acid (RNA) and a protein coat (capsid). The nucleic acid is the genetic material of the virus, and the capsid mainly plays a role in protecting the viral nucleic acid[8⇓~10]. In addition to the capsid of COVID-19, it also has an envelope and spike structure, which can not only protect the capsid, but also assist the virus to infect the host during infection[11]. Based on the structure of the virus, there are three main inactivation mechanisms: (1) to destroy the envelope and spike structure outside the virus capsid, so that the virus can not penetrate the host cells and lose infectivity; (2) destroy the protein shell of the virus, so that the virus loses its structural support, and then the nucleic acid in it is destroyed; (3) Destroy the nucleic acid of the virus, so that the genetic material of the virus is damaged and loses its reproductive capacity.
Water treatment disinfection technology mainly includes drinking water disinfection and urban sewage disinfection technology, aiming at killing most pathogenic microorganisms (including bacteria, viruses, protozoa, etc.) In water which are harmful to human health. China's current "Sanitary Standard for Drinking Water" (GB5749-2006) requires that "drinking water should not contain pathogenic microorganisms", which means that the limit including all kinds of viruses is zero. In addition, the "Discharge Standard of Pollutants for Municipal Sewage Treatment Plants" (GB18918-2002) also clearly stipulates the discharge standard of coliform bacteria[12][13]. Therefore, the sterilization and virus inactivation means of water treatment disinfection technology are also widely used. At present, the traditional disinfection method with chlorine preparation as the core is still the main technical measure of water disinfection. Chlorine (free chlorine), hypochlorous acid and sodium hypochlorite (HClO and NaClO), chlorine dioxide (ClO2), chloramines (NH2Cl, NHCl2 and NCl3) and ozone (O3) can be used as water disinfectants[14]. For example, the widely used 84 disinfectant is a chlorine-containing disinfectant with sodium hypochlorite as its main component, which is mainly used for disinfection of object surfaces and the environment. The mechanism of virus inactivation by chemical disinfectants includes: disinfectants inactivate viruses through direct lethal damage to nucleic acids; Disinfectants denature the protein capsid of the virus, so that the nucleic acid loses its protective barrier and the virus can not adsorb and penetrate into host cells to complete proliferation, so as to inactivate the virus[15]. In addition, ultraviolet disinfection is also a commonly used method of inactivating bacteria and viruses. The principle is that ultraviolet rays directly damage the DNA and RNA of viruses through the external structure[16].
At present, chlorine and other chemical agents disinfection and ultraviolet disinfection to kill the virus is still the main means to cut off its transmission route. However, the traditional disinfection technology has the following disadvantages: firstly, the traditional chlorine-containing disinfectant has low efficiency and poor sustainability, and chlorine preparations must be applied or sprayed many times to maintain its continuous disinfection, and the oxidation potential of chlorine preparations and ozone is not as good as that of free radicals (such as hydroxyl radicals), so the oxidation capacity is weaker than that of advanced oxidation technology[14,17]. Secondly, traditional disinfection measures consume a lot of energy and are relatively complex to operate, which requires the assistance of supporting facilities. For example, ultraviolet disinfection needs ultraviolet light source, which requires a lot of energy consumption, and the effect is affected by light transmittance and suspended solids concentration, so the operation and maintenance costs are high. Ozone preparation is costly and requires an ozone generator, and high-purity ozone requires oxygen as a precursor for preparation[18]. In addition, chemical oxidant disinfection process is easy to cause pipeline corrosion and aging problems, and the maintenance cost is also high. Moreover, traditional disinfectants, especially chlorine, are prone to react with trace organics in water to form carcinogenic halogenated disinfection by-products (DBPs)[14]. Ozone disinfection is greatly affected by water quality, and its by-products are complex and unknown toxicity[19]. To sum up, it is necessary to explore new disinfection methods. The ideal disinfectant should have the ability of broad-spectrum sterilization and virus inactivation, lasting disinfection, no or very few toxic and harmful disinfection by-products, safe, convenient and low cost.
Nanotechnology, with nanomaterials as its core, has been widely used in water disinfection and has shown its unique advantages[20]. As shown in Figure 1, the main mechanisms of nanotechnology disinfection include: (1) the heterogeneous reaction of nanomaterials produces strong oxidative free radicals (· OH, SO4·-, · , etc.) To attack the nucleic acid and protein of the virus, causing the disintegration of the virus and even the oxidative degradation of its components (Figure 1A);(2) The release of toxic ions (such as Ag+, Au+, and Cu2+) from nanomaterials affects the normal metabolism of viruses or blocks important biochemical functions (such as binding to host cells) (Figure 1b); (3) The unique and diverse microstructure of nanomaterials causes structural effects such as piercing, cutting, and winding on viruses, resulting in structural damage and inactivation of viruses (Figure 1C). Compared with bulk materials, nanomaterials have higher surface energy and reactivity due to their four effects of surface and interface effect, small size effect, quantum size effect and macroscopic quantum tunneling, and have more advantages in disinfection. The characteristics and advantages of nanotechnology disinfection are mainly reflected in the following aspects: (1) large specific surface area and high surface energy, which make the interface between materials and viruses fully interact and greatly improve the disinfection efficiency; (2) the strong oxidative free radicals produced by addition advanced oxidation have higher oxidation capacity than traditional chemical disinfectants, and can quickly inactivate, crack and even deeply mineralize viruses; (3) Some technologies, such as nano-photocatalysis mediated by sunlight, can continuously produce free radicals for disinfection with strong durability; (4) no additional energy and complex auxiliary equipment are generally required, the operation is simple, the control is easy, and the operation cost is low; And (5) no disinfection byproduct is generate, and that risk of green and secondary pollution is small. Therefore, nanotechnology also has a foreseeable application prospect in the inactivation of novel coronavirus SARS-CoV-2[21].
Based on the structure and transmission characteristics of the novel coronavirus SARS-CoV-2, this paper will comprehensively review the application of nanotechnology in virus killing, and explore the feasibility of this technology in the application of novel coronavirus killing. The specific objectives of this review include: (1) to clarify the structural characteristics of COVID-19 and its survival characteristics in the water environment of important vectors; (2) To clarify the traditional sewage disinfection technology and the killing mechanism of viruses (especially COVID-19), and to compare and summarize the advantages and disadvantages of environmental nanotechnology; (3) The application of photocatalysis, heterogeneous catalysis, ion dissolution and structural effect of nanomaterials to kill viruses is described in detail, and the mechanism of virus inactivation induced by nanomaterials is elaborated in depth. (4) To explore the development direction of new nanomaterials suitable for efficient killing of novel coronavirus. This review can provide guidance for the development of new nanotechnology for efficient inactivation of novel coronavirus, so as to achieve large-scale practical application in the future, which has important theoretical and practical significance for epidemic prevention and control and cutting off possible transmission routes of the virus in the future.
2 Novel coronavirus and sewage disinfection technology
2.1 Novel coronavirus structural composition
Coronavirus (CoV) belongs to Nidovirales, Coronaviridae, Coronavirus. It is an enveloped, single-stranded, positive-strand RNA virus that causes respiratory, intestinal, hepatic and neurological symptoms. The origin of human coronavirus can be traced back to the first strain of human coronavirus (HCoV) isolated in 1965, which was considered to be an insignificant pathogen in the early days, because it would be rapidly inactivated without host, and the risk of disease to healthy people was very low. However, in the 21st century, three highly pathogenic HCoVs have emerged among the coronaviruses present in animal hosts, which led to Severe Acute Respiratory Syndrome (SARS) in 2003, Middle East Respiratory Syndrome (MERS) in 2012, and the ongoing COVID-19 epidemic in 2019[10,22⇓ ~24]. These three diseases, which can lead to serious illness and even fatal, have brought a new understanding of the seriousness of coronavirus infection. At the same time, it is also recognized that the HCoV can remain active in the environmental media (water and aerosols) for a considerable period of time after leaving the host, so it is particularly important to kill the virus in the media and block the transmission route. Like SARS coronavirus (SARS-CoV) and MERS coronavirus (MERS-CoV), the pathogen causing the 2019 novel coronavirus pneumonia also belongs to the coronavirus genus. The World Health Organization (WHO) officially named it 2019-nCoV in January 2020, while the International Committee on Taxonomy of Viruses (ICTV) proposed to name it SARS-CoV-2. In order to maintain the consistency of this paper, the academic name of SARS-CoV-2 is adopted in this paper[25]. Phylogenetic analysis showed that the length of SARS-CoV-2 was 29891 bp, which belonged to β-CoV and shared 79. 5% sequence similarity with SARS-CoV[26].
Viruses, unlike bacteria or protozoa, are obligate parasites that do not have a complete cellular structure. The novel coronavirus SARS-CoV-2 consists of nucleic acid RNA and protein. Specifically, as shown in Figure 2, SARS-CoV-2 particles are spherical with a diameter of about 125 nm. The prominent feature is that there are many regularly arranged protrusions on the surface of the particles, which are named "coronavirus" because they look like "crowns" (Figure 2a and 2b)[23,27]. Coronavirus particles contain four major structural proteins (Fig. 2a-d), namely spike protein (S), membrane protein (M), envelope protein (E) and nucleocapsid protein (N)[10,23]. The S protein consists of two subunits: S1 recognizes and binds to the host receptor, and S2 promotes fusion between the viral envelope and the host cell membrane. The S protein guides the coronavirus into the host cell by providing binding and fusion of the virus at the host cell membrane, which is the first stage of the virus life cycle[28]. Studies have shown that the S protein of SARS-CoV-2 binds to angiotensin-converting enzyme 2 (ACE2) in human cells (figs. 3A and 3B), and S1 binds more closely to ACE2 (fig. 3B)[8,9,29][22,30,31]. In addition, the ability of S1 in SARS-CoV-2 virus to bind to ACE2 is 10 to 20 times higher than that of SARS-CoV, which caused the SARS epidemic in 2013, which also proves the reason why SARS-CoV-2 virus is highly infectious and pathogenic[32]. Li Lanjuan and Li Sai et al. accurately analyzed the three-dimensional internal structure of the novel coronavirus through cryo-electron microscopy (as shown in Figure 2C and Figure 2D), and clarified how the virus accumulates its single RNA of about 30 kb in a lumen with a diameter of about 80 nm.The spike protein (S) is the "key" for the virus to invade human cells, and most of the current research and development of vaccines and antibodies focus on this protein, so the results of its related structural analysis provide an important theoretical support for the subsequent development of vaccines and inactivation in media[33][22].
2.2 Survival and transmission characteristics of novel coronavirus in aquatic environment
Once the virus is separated from the host and enters the natural environment, it can not replicate and proliferate itself, but it can survive in the natural medium for a certain period of time, usually in days[34]. A large number of virus particles are discharged into sewage mainly through the feces and vomit of infected people, and then into receiving natural water bodies through untreated or inadequately treated sewage. Viruses usually outnumber bacteria in all aquatic ecosystems, including wastewater[35]. This makes urban sewage one of the most concentrated sources of viruses[36]. The effective removal of viruses in wastewater is closely related to the safe discharge or reuse of treated water, which is an important guarantee for the safety of water environment.
According to the Guidelines for Drinking-Water Quality (fourth edition), viruses with high health risks in Drinking Water include enterovirus, hepatitis a virus, hepatitis E virus, rotavirus, norovirus and Sapporo virus. However, there are few reports on the characteristics and behavior of coronavirus in drinking water. WHO believes that the health risks in drinking water are uncertain or lack of evidence[37]. The current Sanitary Standard for Drinking Water (GB 5749-2006) in China does not limit the maximum allowable concentration of viruses, but requires that the residual free chlorine in finished water should not be less than 0. 3 mg/L and the contact time should not be less than 30 min[12]. According to experience, the effective concentration of this disinfectant can meet the requirement of virus inactivation rate greater than 3-log[38].
For the novel coronavirus SARS-CoV-2, it can spread rapidly during an outbreak because the main mode of transmission of coronavirus between people is human-to-human transmission through respiratory droplets[1,11,39]. Drainage systems, including urban domestic sewage drainage systems and medical wastewater drainage systems, are also important vectors for the transmission of coronavirus, especially during outbreaks, the harm caused by transmission through sewage (that is, "fecal-oral" transmission) will far exceed the normal level[36]. Studies have shown that it takes 1.5 and 1.7 days for SARS-CoV-2 to reach 90% inactivation in wastewater and tap water at 20 ℃[7]. In addition, SARS-CoV-2 virus could survive in feces for 7 days and in sputum for 24 hours[40][41,42]. The March 2003 outbreak of SARS involving more than 300 people in a high-rise residential area in Hong Kong was closely linked to a faulty sewage system, and the study found the virus in the feces of infected visitors.May be transmitted to other occupants of the building by droplets and aerosols of commode water that enter multiple apartments through defective toilet plumbing and floor drains[43a]. In February 2020, Zhong Nanshan and others at the National Key Laboratory of Respiratory Diseases of China also successfully isolated live novel coronavirus from the feces of a severe case of novel coronavirus infection, indicating that the water contaminated by the feces of the infected person may become a vector for the transmission of novel coronavirus[43b]. There are relatively few studies on the fecal-respiratory pathway (i.e., "fecal-oral" transmission), but the high stability of the virus in water increases the risk of transmission through fecal-contaminated water[44]. It can be seen that the new coronavirus is a possible intestinal pathogen, and its epidemic transmission may have an important relationship with water and wastewater. In sewage treatment, especially in high-risk areas, it is necessary to kill the virus as thoroughly as possible and cut off its transmission through water media.
2.3 Sewage disinfection technology suitable for novel coronavirus
Facing the severe epidemic situation, China's environmental protection department has issued a guidance document to strengthen the safety of the water environment. On February 1, 2020, the Ministry of Ecology and Environment issued the Technical Plan for Emergency Treatment of Medical Sewage Contaminated by New Coronavirus (Trial), requiring urban sewage treatment plants to strengthen disinfection work and take measures such as adding disinfectants or ozone and ultraviolet disinfection to prevent the spread of new coronavirus through sewage. On February 11, 2020, the Water Special Implementation and Management Office of the Ministry of Housing and Urban-Rural Construction issued the Operational Management Recommendations for Strengthening Virus Removal and Control in Drinking Water Plants.Both the United States and the Third People's Hospital of Shenzhen have detected positive results of coronavirus in the excreta of confirmed patients with novel coronavirus infection, which should be given sufficient attention and appropriate measures should be taken to prevent cross-infection.
For municipal wastewater treatment plants, although they can effectively remove particulate matter, degrade organic matter and reduce pathogenic microorganisms, there may still be a certain concentration of virus particles in the effluent, which will cause health risks to the exposed population if the follow-up treatment is improper. At present, wastewater treatment plants mostly use ultraviolet, chlorine or ozone disinfection processes, which can effectively inactivate some viruses, but the long survival time of coronavirus in water still poses a challenge for its effective removal. For example, coronavirus can remain infectious in water and pasteurized sewage for a long time compared to the survival rates of transmissible gastroenteritis virus (TGEV) and mouse hepatitis virus (MHV), suggesting that contaminated water is a potential vector for human exposure if aerosols are produced[45]. In addition, the survival time of SARS-CoV-2 in water is also related to the temperature of water. It takes 1.5 and 1.7 days to reach 90% inactivation rate in wastewater and tap water at 20 ℃, which means that another 10% of SARS-CoV-2 virus may have a higher survival time, while it takes only 15 and 2 minutes to inactivate 90% of SARS-CoV-2 virus in wastewater at 50 ℃ and 70 ℃[7][7].
The COVID-19 outbreak has posed new challenges to disinfection measures for drinking water and urban sewage in countries around the world. In the case of various disadvantages of traditional disinfection measures, it has become a necessary trend to seek new and efficient disinfection technology. For example, photocatalytic technology has attracted great attention because of its strong ability, low probability of disinfection by-products and environmental friendliness. In recent years, scholars have carried out extensive research on the development of photocatalytic materials, the optimization of reaction conditions, the design of reactors and the mechanism of photocatalytic inactivation of pathogenic bacteria. MS2 bacteriophages, the virus substitutes for human enteropathogens, are generally resistant to UV and light Fenton, but the use of photocatalytic materials such as TiO2 can significantly improve the inactivation effect of MS2 in water under UV irradiation[46]. The dosage of catalyst has a great influence on the inactivation of bacteriophage MS2. For example, the inactivation of bacteriophage MS2 in the effluent of sewage treatment plant is not effective at low concentration of TiO2. When the concentration of TiO2 is increased to 200 mg/L, the inactivation rate of MS2 in the effluent of sewage treatment plant can reach 4. 76-log after ultraviolet irradiation for 6 H[47]. The presence of TiO2 under UV light can also play a better inactivation effect on novel coronavirus SARS-CoV-2[48]. However, compared with other pathogens (such as bacteria), there are relatively few studies on the application of new photocatalysis technology in the inactivation of viruses in water, especially whether nano-photocatalysis can effectively kill SARS-CoV-2 remains to be explored.
2.4 Evaluation mechanism and method of novel coronavirus inactivation
At present, there are many detection methods and inactivation evaluation methods for novel coronavirus, including morphological observation method, culture counting method and molecular biology detection method, as follows[49].
(1) Morphological observation refers to the use of microscopic techniques to observe the morphological characteristics of viruses. Because of the small structure of the virus, the morphology of the virus can not be directly observed by ordinary light microscope, so it is necessary to study the virus by means of electron microscope. For example, scanning electron microscopy (SEM) and environmental scanning electron microscopy (ESEM) can be used to observe the overall morphology of viruses and their existence in environmental media. The internal structural features of the virus can be observed by transmission electron microscopy (TEM) (fig. 2a); Atomic force microscopy (AFM) can measure the interaction force between virus and receptor, and study the pathogenic mechanism of virus. The three-dimensional structure of the virus can be reconstructed by cryo-electron microscopy (CEM) (Fig. 2C and 2D)[23,27,33].
(2) The culture method is a classical method for virus counting, and the number of viruses is usually expressed by titer (the number of hosts infected by virus suspension per unit volume). Virus titer was determined by counting the number of plaques (PFU) formed after virus infection of host cells on a plate. Alternatively, that virus can be quantify using the median tissue culture infective dose (TCID50), I. e., the amount of virus require to cause half of the cell death. Although the culture method can accurately determine the number of active viruses, different host cells need to be selected for different viruses, and some viruses can not be cultured, which limits the use of culture counting method. In addition, the culture method has the disadvantages of long cycle, high operation requirement, high cost and the like.
(3) The main methods of molecular biological detection of viruses are real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) and high-throughput sequencing (NGS). These two methods need to extract the DNA or RNA of the sample before detection. At present, the nucleic acid extraction method is relatively mature, and there are many commercial reagents for nucleic acid extraction on the market, which are simple and easy to operate. The RT-qPCR method is to amplify the target viral fragments in nucleic acid samples and quantify them with fluorescent probes or dyes. When using this method, it is necessary to design specific amplification primers according to the nucleic acid sequence of known viruses, and then detect them. This method is fast and sensitive, and can complete the detection in a few hours, and trace amounts of virus can also be detected. NGS method is a newly developed sequencing method in recent years, which can quickly (hours to days) obtain all the nucleic acid sequence information in the sample. Different sequencing platforms have different principles and technologies. At present, the mainstream platforms include Illumina, Oxford nanopore and PacBio. After obtaining the sequencing data, the nucleic acid sequence is compared with the known virus sequence, and then the virus sequence is identified. Because of the rapid, sensitive and accurate advantages of molecular biology methods, RT-qPCR and NGS methods have been used to confirm cases in the "New Coronavirus Pneumonia Diagnosis and Treatment Program (Trial Seventh Edition)"[4]. However, because the above methods are based on the nucleic acid of the virus, it is impossible to determine whether the virus is still active and infectious.
3 Application of Nanotechnology in Virus Inactivation and Its Feasibility Analysis in Novel Coronavirus Inactivation
3.1 Application of Nanomaterial Heterogeneous Advanced Oxidation Technology Based on Free Radical Attack to Virus Inactivation
New disinfection technologies, such as the advanced oxidation technology of functional nanomaterials addition, have good application advantages because of the large generation of free radicals and the interface that can provide high reaction activation energy. As mentioned above, the biomolecules composing the novel coronavirus SARS-CoV-2 are protein and RNA, and the cysteine residue sulfhydryl group at the end of the protein and the aromatic group of the aromatic side chain are easily oxidized, while the peptide bond of α-carbon also tends to react, resulting in the collapse of the protein structure. Free radicals can also destroy RNA through reactions on the backbone ribose ring, where guanine and adenine are highly susceptible to oxidative damage. Previous studies have shown that reactive oxygen species (ROS) can inactivate coronaviruses, and a large number of ROS in cells can lead to macromolecular oxidation and apoptosis, while SARS-CoV-2, as a single-stranded RNA virus, has a tendency to be oxidized in a high concentration of free radicals[50][51]. This also provides a theoretical basis for novel coronavirus inactivation by nanomaterial advanced oxidation system.
3.1.1 Nanometer photocatalysis technology
Ultraviolet (UV) disinfection is the use of appropriate wavelength of Ultraviolet light to destroy microorganisms (pathogenic bacteria and viruses) for radiation damage, damage the molecular structure of DNA or RNA, resulting in bond-to-bond splitting, cross-linking between strands, the formation of light-induced reaction products to change the activity of nucleic acids, resulting in microbial inactivation to achieve the effect of disinfection[52]. Although UV disinfection has a broad spectrum and fast reaction speed, its efficiency is low, and different viral substances have different UV response degrees. In addition, it requires a large dose of light radiation and is not persistent, so it is easy to cause the revival of viruses and bacteria and reduce the inactivation effect. Studies have shown that ultraviolet disinfection technology has a certain inactivation effect on SARS-CoV-2[48,53,54]. Fig. 4 shows the inactivation effect of SARS-CoV-2 with an initial concentration of 5×106TCID50/mL under two UV irradiations. After 9 min UV exposure, SARS-CoV-2 can achieve 100% inactivation (Fig. 4A), and the inactivation rate of virus can also reach 50% after 1.4 min UV exposure (Fig. 4B)[53].
It was also found that UVC (254 nm) had better inactivation effect than UVA (365 nm), and the irradiation intensity of UVC needed to reach the 1048 mJ/cm2 to completely inactivate COVID-19 (Figures 4C and 4D). Therefore, UV disinfection can be used as a short-term, easy-to-deploy and highly applicable technology to limit the spread of SARS-CoV-2 and effectively contain the COVID-19 epidemic[5].
Photocatalytic disinfection technology developed on the basis of UV disinfection has more advantages, which is a green, energy-saving, efficient, safe and environmentally friendly and economical technology. The catalyst produces a large number of ROS under the action of light, which can efficiently inactivate pathogenic viruses and bacteria, and is less affected by the pH value and temperature of water[55]. Moreover, if sunlight can be directly used for photocatalysis, it will greatly save costs and improve energy efficiency. Therefore, photocatalytic technology, as the core of heterogeneous advanced oxidation technology, has attracted wide attention of scholars in the field of water treatment and disinfection of pharmaceutical wastewater, and has shown broad market application prospects. Photocatalysts (mostly semiconductors) are excited by light to form photogenerated carriers (electron-hole pairs), and can initiate radical chain reactions to generate a variety of active oxygen species, such as · OH, · , singlet oxygen (1O2) and hydrogen peroxide (H2O2) (formulas (1) to (6))[17,20,56]. Furthermore, the protein, nucleic acid, saccharide, lipid and other components of the virus can be destroyed to inactivate the virus. The oxidation potential of free radicals is usually higher than that of chemical oxidants such as chlorine preparations (see Table 1), so the ability to kill viruses is stronger. Because of its large specific surface area and high surface energy, nano-photocatalytic materials can produce free radicals more effectively and provide more sufficient contact interface, thus improving the disinfection efficiency.
h+ + H2O → ·OH + H +
OH-(表面)+ h+→ ·OH
·OH + ·OH→ H2O2
O2 + e-→ ·
· + e- + 2H+→ H2O2
H2O2+ e- + H+→ ·OH+ H2O
Nano TiO2 particles can show high inactivation efficiency against SARS-CoV-2 under UV irradiation[48]. The researchers used the HCoV-NL63 strain, which is highly similar to the SARS-CoV-2 virus, as an alternative research object. At the initial concentration of 2.1×106TCID50/mL, under the irradiation of 254 nm UVC, the TiO2 nanoparticles could significantly improve the inactivation efficiency of the virus compared to no material addition, achieving 100% virus inactivation in 1 min (Figure 5). This study demonstrated the unique performance advantages of nano-photocatalysts in the application of novel coronavirus inactivation. In addition, nanotechnology can not only be used to kill SARS-CoV-2 virus in the air or contact surface environment, but also be effectively applied to the killing of personal protective equipment such as masks[21].
The generation of the main free radicals in the photocatalytic reaction and the mechanism of action with viruses are as follows.
(1) hydroxyl radical (· OH) and superoxide radical (· )
· OH and · are the most important reactive species in the disinfection of nanomaterials photocatalytic technology, and their main formation mechanisms are shown in formulas (1) ~ (6)[17,56,65⇓⇓ ~68]. · OH is strongly oxidizing (see Table 1) and non-selective, and can undergo redox reactions with a variety of organic compounds in the virus structure. Because the virus has no cellular structure, the two free radicals can inhibit and inactivate the virus by destroying the protein capsid (composed of polypeptide chains), the nucleic acid core (composed of DNA and RNA) and the envelope (containing proteins, phospholipids and cholesterol). The novel coronavirus SARS-CoV-2 is composed of RNA and protein (Figure 2), so the active species generated by nano-photocatalysis can effectively attack and degrade the organic substances in its structure, and its inactivation efficiency is much higher than that of conventional chlorine-containing disinfection technology.
(2) singlet oxygen (1O2)
Singlet oxygen (1O2) has strong penetrability and diffusibility, and is easy to interact with various biological components such as proteins, amino acids and nucleic acids, which destroys the outer structure of the virus and leads to the inactivation of the virus[68⇓~70]. The 1O2 is mainly obtain from two ways, one is a dye photosensitization method, wherein exciton generated by photoexcitation of a dye type photosensitizer can transfer energy to O2 molecules to form that 1O2. The disinfector for SARS virus has been developed by the Third Military Medical University, which can realize the combination of photosensitizer and guanine in SARS virus nucleic acid under visible light irradiation, and induce the production of 1O2 under specific red light wavelength irradiation, so as to damage the envelope and inactivate the virus[71]. Another method is to convert the energy received by O2 molecules into 1 under illumination based on the unique defect structure and localized surface plasmon resonance (LSPR) effect of nanomaterials such as Au, Pd, CuS and W18O49. In addition, photothermal therapy (PTT) and photodynamic therapy (PDT), which are based on the generation of 1O2 mediated by nano-photocatalysis, have attracted wide interest of researchers in recent years due to their non-invasive properties in the field of cancer treatment, and the light absorption of materials in the near infrared (NIR) is a prerequisite for PTT and PDT agents[73,74]. Therefore, the application of photothermal effect with 1O2 as the core in the killing of novel coronavirus has its unique advantages.
(3) Hydrogen peroxide (H2O2)
H2O2 is a common disinfectant in the pharmaceutical and industrial fields. First of all, because of its own oxidation (oxidation potential 1.8 V, see Table 1), it can directly destroy the structure of the virus and change the balance of substances inside and outside the protein capsid, resulting in the death of the virus; On the other hand, H2O2 can be decomposed to produce reactive oxygen species (such as hydroxyl), and then kill viruses through the strong oxidation of free radicals[75]. However, when some pathogenic microorganisms are stimulated by H2O2, they will produce catalase, which will quickly decompose H2O2 into water and oxygen, thus reducing the effect of action. It can be seen that the inactivation efficiency of H2O2 alone is low, and it is necessary for nano-materials photocatalysis to cooperate with H2O2 to produce free radicals to improve the inactivation efficiency of pathogenic microorganisms[52]. Therefore, H2O2 can not only inactivate viruses by itself, but also be used as the precursor of hydroxyl radicals in photocatalytic disinfection systems. It has been reported that iron-based, carbon-based, MOFs and perovskite photocatalytic materials cooperate with H2O2 to inactivate viruses, which makes it possible to apply this technology to the inactivation of SARS-CoV-2 virus[76].
Commonly used photocatalytic disinfection nanomaterials mainly include the following three categories.
(1) Ultraviolet photocatalysis nanomaterials. Since Matsunaga et al. Reported the photocatalytic bactericidal performance of TiO2 nanomaterials irradiated by UVA light source in 1985, nano-photocatalysts have been widely developed and applied in the field of disinfection[77]. At present, TiO2 is still the most widely used photocatalyst, and nanoscale TiO2 can greatly improve the quantum efficiency. The band gap of the TiO2 is 3. 2 eV, which means that the photogenerated carriers can be excited by ultraviolet light with wavelength less than or equal to 387. 5 nm, and then active species can be formed on the surface to kill viruses[78]. In addition, a variety of new nano-photocatalysts have been gradually developed and applied to the killing of viruses, such as modified titanium-based nano-photocatalysts, which can effectively inactivate MS2 phage, norovirus, H1N1, Qβ phage, PL phage and hepatitis B virus under ultraviolet light[70][68,70,79⇓ ~81]. The main inactivation mechanism of UV-driven nano-photocatalyst virus is based on the destruction of the capsid protein of the virus by strong oxidizing holes (h+) and generated ROS (including · , · OH, 1O2, and H2O2, etc.) To achieve the inhibition and killing of the virus (Figure 1A). In addition, the virus inactivation caused by the nano-photocatalytic material may also include the toxic effect of the metal loaded on the nano-photocatalytic material (Figure 1b) and the physical damage effect caused by the size effect (Figure 1C)[70]. As mentioned above, the excellent inactivation effect of nano TiO2 particles on SARS-CoV-2 under UV irradiation has been confirmed, which further proves the application prospect of nano photocatalytic materials in cooperation with UV irradiation for the inactivation of SARS-CoV-2 virus[48].
(2) Visible light catalytic nanomaterials. This kind of material should have a suitable gap band (generally < 3 eV), so it can use visible light (wavelength > 420 nm), such as non-metallic photocatalyst graphite phase carbon nitride (g-C3N4), metal photocatalyst bismuth semiconductor series, two-dimensional photocatalyst MoS2 and so on[68⇓~70]. g-C3N4 is a hot visible-light photocatalyst with a band gap of 2. 7 eV, so it can efficiently use visible light to inactivate viruses[82]. In addition, since the top energy level of its valence band is 1.57 eV at pH = 7, it can not produce · OH, so it can only inactivate the virus through the direct oxidation of photogenerated holes or the · generated by the combination of photogenerated electrons and adsorbed oxygen, and further through the chain reaction to produce ROS such as (·OH/H2O2) (as shown in Figure 6a). Visible light photocatalysis of g-C3N4 has demonstrated the inactivation properties of virophage MS2, and radical trapping experiments have shown that photogenerated electrons and their derivatives, , are the main species responsible for viral inactivation (fig. 6a)[82]. The capsid protein of MS2 virus is destroyed by free radical attack, which causes the internal genetic material to flow out and be decomposed, resulting in the inactivation of the virus. The main killing methods are: deformation caused by nanomaterials, free radical oxidation of protein capsid and destruction of RNA (Fig. 6B)[82]. Recently, it has been reported that WO3 can effectively kill SARS-CoV-2 under visible light. After 6 hours of visible light irradiation at room temperature, SARS-CoV-2 virus is not affected. However, the addition of WO3 photocatalytic material can effectively kill SARS-CoV-2 virus, resulting in the reduction of virus concentration from (5.93 ± 0.38) to (3.05±0.25)logTCID50/mL[83].
And (3) simulate that solar catalytic nano material. Such materials shall have a high utilization rate of both ultraviolet and visible light bands. For example, nano FeOx photocatalytic materials can effectively remove MS2 bacteriophage under simulated sunlight[84]. In addition, recently reported metal-organic frameworks (MOFs) have been widely used in the field of water disinfection due to their large specific surface area, nanoporous structure, high porosity, highly dispersed active sites, tunable pore size and functional structure. The MOFilter nanocrystalline film material prepared with ZIF-8 as the substrate can catalyze molecular oxygen in the air to generate under sunlight irradiation, and then capture water molecules in the air to continuously generate hydrogen peroxide in situ (fig. 7A), which can achieve a killing rate of more than 99.99% against coronavirus, poliovirus and H1N1 influenza virus (fig. 7B)[85]. Therefore, the material can be used as a protective layer of masks, protective clothing and air conditioning filter elements, thereby blocking and killing viruses, and has great application prospects. It has been confirmed that MOF material MIL-177-HT can achieve 50% inactivation of SARS-CoV-2 virus after 30 min of photocatalysis under indoor natural light, while indoor light has no effect on virus inactivation[86].
To sum up, nano-photocatalytic technology can be applied to the inactivation of the novel coronavirus SARS-CoV-2.Further consideration can be made from the following aspects: (1) development of new solar-driven photocatalyst materials, which can be excited to produce active species under sunlight, thus realizing the convenient use of materials, and the direct use of sunlight can significantly reduce energy consumption and cost; (2) that photocatalyst material modify by the photosensitizer is utilize to directionally generate the 1O2, and due to the long service life, strong penetrability and strong diffusibility of the 1O2, the photocatalyst material is easy to pass through a protein outer shell lay of the virus to react with nucleic acid, so that the virus inactivation efficiency is improved; (3) Drawing lessons from the non-destructive characteristics of photocatalytic-mediated photothermal therapy (PTT) and photodynamic therapy (PDT) in the field of cancer treatment, we try to use the characteristics of nano-materials in the near-infrared light absorption to produce 1O2 in the reaction process and then inactivate the novel coronavirus; (4) develop photocatalysis coupling other advanced oxidation systems, such as photocatalysis synergetic Fenton reaction, photocatalysis coupling persulfate system, etc., to improve the generation efficiency and yield of free radicals and achieve efficient killing of viruses; (5) Organic-inorganic hybrid materials are formed by compounding anti-novel coronavirus drugs with functionalized photocatalytic materials, which can produce free radicals under light conditions and cooperate with the high efficiency of drugs, and are expected to greatly improve the inactivation ability of novel coronavirus.
3.1.2 Advanced Oxidation Technology for Producing Sulfate Radical by Nanomaterial Heterogeneous Excitation
In recent years, the advanced oxidation system established by sulfate radical (SO4·-,E0=2.5~3.1 V) as a substitute for hydroxyl radical (E0=1.8~2.7 V) has attracted wide attention of scholars, and has been widely used in pollutant degradation and water disinfection[63,65,87][17,56]. Compared with ·OH,SO4·-, it has a wide pH range (2-11), longer half-life (40 μs), higher selectivity and faster reaction kinetics[88⇓~90]. Sulfate radicals are mainly generated by the excitation of monopersulfate (PMS, HS ) and peroxodisulfate (PS,S2), which are activated by UV, ultrasound, heat or nanocatalysts[91]. As an important part of environmental nanotechnology, the nano-catalysts used to activate persulfate to produce SO4·- have attracted much attention. These catalysts include metal nanoparticles, nano-metal oxides, nano-mixed metal oxides and non-metallic nanomaterials[92,93]. Nanocatalysts have unique advantages in activating persulfate, including high activation efficiency, controllable cost, high material reusability, good physical and chemical stability and environmental friendliness. Cobalt and its compounds are considered to be the most effective heterogeneous catalyst to activate persulfate, which can activate SO4·- to degrade organic pollutants and disinfect, and its effect is better than that of traditional Fenton reaction at neutral pH and low reagent dosage[94,95][76]. Hydroxyl cobalt (Co(OH)+) in a cobalt material in a complex state is considered to be the most important species for exciting PMS/PS, and the reaction process of generating SO4·- by catalytic excitation and the cyclic catalytic process of the nano material are shown in the following formulas (7)- (11)[96,97][63]. Meanwhile, in the liquid phase system, SO4·- will also react with H2O(k<1×103M-1·s-1) or OH-(k=6.5×107M-1·s-1) to generate hydroxyl (see formula (8)), and the generated Co (III) will further react with PMS to promote the effective recycling of nanomaterials[98]. The SO4·- generated in the heterogeneous phase advanced oxidation system has been proved to be capable of effectively degrading organic pollutants which are difficult to remove in water, and can kill viruses in a wide pH range in the same way, and the long existing life can continuously react with surface proteins or internal nucleic acids of the viruses for a long time so as to degrade the viruses[99,100].
≡Co-OH+ + HS → ≡CoO+ + H2O+ SO4·-
OH- + SO4·- → S + ·OH
≡CoO+ + 2H+ → ≡Co 3+ + H2O
≡Co3+ + HS → ≡Co 2+ + S · + H+
≡Co2+ + H2O → ≡Co-OH + + H+
At present, the reports on the application of SO4·- in virus killing are very limited, but the existing studies have confirmed the high efficiency of the advanced oxidation system in sewage disinfection. For example, the Fe/thermal/UV triple process activation of sodium peroxodisulfate (PDS) can effectively generate SO4·- and achieve 100% removal of MS2 phage in the order of 106 within 10 min, and the reaction rate between MS2 virus capsid protein and SO4·- is higher than that of other biomolecules (such as lipids), thus achieving rapid virus inactivation reaction kinetics[101]. In addition, SO4·- also show selectivity to viral component molecules under certain conditions. The production of SO4·- by Cu (Ⅱ)/PMS system can cause the synergistic inactivation of Escherichia coli and MS2, which is mainly attributed to the oxidative stress caused by free radicals (SO4·- and hydroxyl radical) in organisms, which also provides a reference for the inactivation of novel coronavirus SARS-CoV-2 by SO4·-[102]. In addition, there was a linear relationship between the loss of virus activity and the exposure time of SO4·-, and the inactivation effect of SO4·- attack for a long time would be more obvious[103]. However, it was also found that although the oxidation ability of SO4·- was higher than that of hydroxyl under neutral and alkaline conditions, because some viruses (such as MS2 and SARS-CoV-2) and SO4·- were negatively charged, electrostatic repulsion would reduce the interfacial contact between them, thus affecting the efficiency of virus inactivation[104][105].
SO4·- has strong oxidation ability and long half-life, and it has the ability to continuously degrade proteins and nucleic acids in viruses. SO4·- have unique advantages in killing novel coronavirus: (1) There are charged or polar residues on the surface of coronavirus, such as long-chain lysine residues with positive charges, which can bind to negatively charged SO4·- through electrostatic interaction, promoting interfacial reactions and causing subsequent deep damage to the virus structure by free radical attack[106]. (2)SO4·- has higher reactivity with electron-rich chemicals, so the peptide bonds in the protein structure of the novel coronavirus are easily selectively attacked by SO4·-, thus achieving efficient inactivation of the virus[107]. (3) The heterogeneous catalysis system of nanomaterials can continuously produce various active substances such as SO4·-, · OH and · to realize the synergistic inactivation of viruses. In the PMS/PS system excited by heterogeneous catalysis of nanomaterials, besides the free radical mechanism, there may also be a non-free radical mechanism, which directly destroys the biomolecular structure of viruses through electron transfer or singlet oxygen generation, providing a variety of possibilities for virus inactivation. For example, human adenovirus can be inactivated by g-C3N4 visible light photocatalysis combined with PMS SO4·-, while pure g-C3N4 photocatalysis can not effectively inactivate adenovirus (inactivation rate < 0.5-log), but after adding PMS, the inactivation rate of adenovirus can reach 5-log in 120 min due to the production of a large number of SO4·-[108]. However, the current research on the inactivation of virus-induced SO4·- production focuses on homogeneous systems.For the heterogeneous system of nanomaterials, the mechanism of free radical production has been explored more and more clearly, but the pathway and mechanism of virus inactivation still need further study.
Ozone (O3) is a highly reactive molecule with an oxidation potential of 2.07 V and a strong oxidation ability[109]. Ozone dissolved in water can also produce more active oxidizing species, such as hydroxyl radicals, through a series of reactions[110]. Ozone and its secondary oxidants have the ability to react with a variety of biomass components (such as proteins) and can destroy the structure of genetic material DNA and RNA, so ozone is widely used in the field of water disinfection. At present, ozone (ozone gas and ozone water) is not only used for drinking water and air disinfection, but also for surface disinfection[111,112]. As a disinfectant, ozone can kill a wide range of pathogens and microorganisms, including bacteria, fungi, cells and viruses (hepatitis virus, influenza virus, norovirus and coronavirus)[31,113,114].
As previously described, the S protein of the SARS-CoV-2 virus binds to the ACE2 receptor in humans and initiates an infectious attack on the human body. In the early stage of the outbreak of the novel coronavirus pneumonia epidemic (COVID-19) and the subsequent epidemic prevention stage, the use of ozone to kill the virus, to a certain extent, inhibits the spread of the virus, and plays an important role in blocking the source of transmission. Tang Yanping et al. from Hubei Medical College observed the disinfection effect of ozone on ward bed units during the epidemic period of novel coronavirus pneumonia. After the disinfection with ozone concentration greater than 500 mg/m3, the hygienic quality of bed units met the requirements of relevant standards, which proved that ozone had a good clinical application prospect in blocking the spread of SARS-CoV-2 virus[114][115]. Clavo et al. reported that the use of ozone treatment can play a very good killing effect on personal protective gear contaminated by SARS-CoV-2 virus. The personal protective gear contaminated by SARS-CoV-2 virus can be well inhibited or killed by ozone treatment at concentrations of 10000, 4000 and 2000 mg/L for 30 s, 5 min and 10 min[116][116][116]. The mechanism of ozone attacking SARS-CoV-2 virus is mainly the direct attack of ozone molecules and the indirect attack of reactive oxygen species generated by ozone (as shown in Figure 8). In terms of direct attack, ozone molecules can rapidly diffuse to the surface of the virus in environmental media (such as aerosol environment and water environment), oxidizing the S protein and M protein on the surface of the virus. As the main binding site of SARS-CoV-2 virus in human body, S protein can greatly reduce the infectivity and pathogenicity of SARS-CoV-2 virus after being attacked and destroyed[31,117,118]. In terms of indirect attack, reactive oxygen species generated by ozone can also kill viruses. As previously described in the part of photocatalytic mechanism, reactive species can react with organic compounds in the virus structure through redox reactions. Because the virus has no cell structure, free radicals can kill the virus by destroying the protein capsid, nucleic acid core and envelope. Nanomaterials with large specific surface area and high reactivity are important catalysts for indirect oxidative disinfection by ozone to produce free radicals.
Ozone has been used for more than a century to disinfect drinking water and water treatment, and has a broad-spectrum inactivation effect on various pathogens and microorganisms. At present, there are mainly four kinds of disinfection methods based on ozonation technology: ozone method, ultraviolet combined with ozone (UV+O3), hydrogen peroxide combined with ozone (H2O2+O3) and nanomaterial catalysis combined with ozone technology. Table 2 compares the performance, effect and applicability of different ozone oxidation technology disinfection methods. Ozone method has good applicability and popularity because of its long history of development, simple operation and other reasons, but its low killing efficiency, expensive supporting equipment and high probability of potential toxic by-products limit its development. Ultraviolet synergetic ozone and hydrogen peroxide synergetic ozone are also widely used because of the formation of free radicals in the system, which improves the killing efficiency to a certain extent. Compared with these three technologies, nanomaterial-catalyzed ozone technology has the highest killing efficiency and low potential toxicity, and has the advantages of reusability and low cost. The nano catalyst can promote the decomposition of ozone, generate hydroxyl radicals with higher activity, and improve the efficiency of indirect oxidation of ozone, thereby having higher inactivation effect; In recent years, nano-heterogeneous catalytic ozone technology has been gradually applied to the field of disinfection, but as a new technology, it still needs to be promoted in the future.
See (12) ~ (14) for the reaction formula of free radicals generated by ozone decomposition catalyzed by nanomaterials[119]. In addition, nanomaterial photocatalysis combined with ozone technology can realize light-mediated chain redox reaction, which can greatly promote the decomposition of ozone to produce free radicals, so it has attracted wide attention of scholars in the field of disinfection[120⇓~122]. Because ozone has strong electrophilic property, it can be well combined with photogenerated electrons excited by nano-materials, thus inhibiting the composition of photogenerated carriers generated by material photocatalysis to the maximum extent, and achieving the purpose of synergistic effect of nano-material catalytic ozone oxidation and photocatalysis[120,122]. After photogenerated electrons and holes are generated by photocatalysis of the nano material (formula (15)), the ozone molecules can accept the photogenerated electrons generated by excitation of the nano material to generate O3·- (formula (16)), and the photogenerated electrons and holes generated by the nano material can also react with oxygen or water to generate free radicals (formulas (18) and (19)).In addition, the above generated free radicals will also generate a series of free radical chain reactions in water (formulas (14) and (17)), so the ROS generated by ozone in cooperation with photocatalysis can effectively inactivate the novel coronavirus SARS-CoV-2 (formula (20)).
O3 + 纳米材料 → 纳米材料-O=O—O·
纳米材料-O3· → 纳米材料-O· + O2
纳米材料-O· + H2O → 2·OH
纳米材料+hv→纳米材料-e-+纳米材料-h+
O3 + 纳米材料-e- → 纳米材料-O=O—O· -
纳米材料-O=O—O·- → 纳米材料-O· - + O2
纳米材料-e- + O2→ 纳米材料-O2·-
纳米材料- h+ + H2O→ 纳米材料-HO· + H
O3/ROS + 病毒(SARS-CoV-2)→ 灭活
Compared with the pure ozone system, the catalytic ozone technology of nanomaterials is more efficient. For example, after the comparative study of the disinfection effect of pure ozone system and volcanic rock material catalytic ozone with nano-pore on municipal effluent, it was found that the pure ozone system had limited effect on the inactivation of JC virus, while the volcanic rock material catalytic ozone system could completely inactivate JC virus in 150 min, because of the generation of ozone · OH[123].
3.2 Disinfection technology of nanometer material ion dissolution
3.2.1 Disinfection Technology of Gold and Silver Nanoparticle Ion Release
Silver nanoparticles (AgNPs) are widely used as antibacterial materials due to their low biological toxicity and broad-spectrum disinfection properties. The antibacterial mechanism of AgNPs is that AgNPs release Ag+ after contacting the bacterial cell membrane and penetrate into the cell interior to form ROS, which destroys the bacterial cell membrane[124]. However, the interaction mechanism between AgNPs and viruses is still in the stage of exploration, and the killing mechanism of AgNPs is related to the type of viruses. It is generally believed that Ag nanoparticles release Ag+, which in turn inactivate viruses by denaturing proteins through reactions with sulfhydryl, amino, carboxyl, phosphate, and imidazole groups[125]. In addition, Ag+ that enter the virus act on base pairs on nucleic acids, causing DNA or RNA to break down[69]. Silver nanoparticles have also been shown to bind to viral envelope glycoproteins and achieve viral inhibition by preventing the binding of HIV-1 envelope glycoprotein gp120 to the disulfide bond region of the host cell receptor CD4 binding domain[126]. Since then, the mechanism of virus inhibition by this combination has been widely demonstrated, for example, the inhibition of HSV-2 virus is achieved by interacting with the sulfhydryl groups present in membrane glycoproteins to eliminate the virus[127]. AgNPs and their functionalized modified materials (such as tannic acid and mercaptoethane sulfonate modification) can prevent the spread of viruses by directly inhibiting virus attachment, penetration, and post-infection transmission[50]. The nanoscale metal silver particles (< 10 nm) have higher virus inactivation efficiency than the bulk materials, as shown in Figure 9, which reveals that the metal nanoparticles bind to the virus to inhibit its infection of eukaryotic cells, and this mechanism provides the possibility for the application of metal nanoparticles in the killing and blocking of SARS-CoV-2 virus. The specific reasons why nanoparticles are more efficient are: (1) metal nanoparticles have high surface energy and are easy to adhere to and combine with viruses; (2) The dissolution kinetics of nano-scale particles, such as Ag and Au, is faster; (3) Silver nanoparticles with extremely small size can penetrate the host cell membrane to target the virus and inhibit the virus replication after attachment.
It has been widely reported that AgNPs are used to kill human immunodeficiency virus (HIV-1), herpes simplex virus (HSV-1, 2, 3), poliovirus type 1 and avian influenza a subtype H7N3 virus[28]. For example, nano-silver particles are used to kill MS2 bacteriophage in gas, which has played a very good role in both filtration efficiency and killing efficiency[129]. Silver nanoparticles (Ag/Al2O3) supported by Al2O3 substrate can effectively destroy the replication and regeneration ability of SARS-CoV-1 (SARS virus) virus, thus blocking its infection of host cells[130]. Therefore, compared with different nanotechnologies and nanomaterials, metal nanoparticles have a strong feasibility to kill SARS-CoV-2[50]. In addition, the photocatalytic materials loaded with AgNPs particles can achieve synergistic disinfection, and the mechanism is as follows: on the one hand, the loading of AgNPs can improve the performance of photocatalysts, because Ag (0), as an excellent conductor, can quickly conduct away the photogenerated electrons generated by the excitation of semiconductors by light and inhibit the recombination of hole-electron pairs; On the other hand, the Ag+ released by AgNPs cooperate with ROS generated by photocatalysis to achieve efficient killing of viruses. Recently, it was reported that in Milan, Italy, a nanomaterial solution containing titanium dioxide and silver ions was used for street disinfection to inactivate SARS-CoV-2 in air, surface water and solid-liquid contact surface to block its transmission route[50]. Therefore, silver-based metal nanoparticles have broad application prospects, whether they are used in water (such as medical and domestic wastewater) or in the atmosphere (air filtration system) to kill COVID-19.
Unlike AgNPs, although gold nanoparticles (AuNPs) can be synthesized by green synthesis methods, they are rarely used as antiviral agents directly, which is related to the fact that the dissolved ions are anionic forms, the poor inactivation effect and the expensive materials. Biocompatible polymers have been used to stabilize AuNPs to prepare effective antiviral agents against HIV-1, H1N1, H3N2, H5N1, dengue virus, bovine viral diarrhea virus and foot-and-mouth disease virus (FMDV)[28]. For example, AuNPs can prevent the replication of foot-and-mouth disease virus (FMDV) in the early stage after entering host cells, and are related to the transcription of host cells, but the exact disinfection mechanism is still unclear[131].
Gold nanoparticles can also be applied to the rapid detection of SARS-CoV-2 virus. The researchers synthesized a material based on gold nanoparticles to bind the RNA of SARS-CoV-2 virus, resulting in a precipitate that can be recognized by the naked eye (Fig. 10), thus achieving the rapid monitoring of SARS-CoV-2 virus and providing a powerful "weapon" for human beings to overcome the COVID-19 epidemic[132]. Due to their high affinity for SARS-CoV-2 viral RNA, AuNPs can also be used to kill viruses, but are more costly than AgNPs.
Therefore, based on the disinfection mechanism of nano-silver and gold particles in other virus fields, we can try to use functionalized nano-gold and silver particles (such as modifying the targeting effect of specific groups) to release gold and silver ions to kill viruses synergistically. Spike glycoprotein (S protein) in novel coronavirus SARS-CoV-2 can be used as an important binding target because it guides coronavirus into host cells by providing virus binding and fusion on the host cell membrane.Therefore, modified gold and silver nanoparticles can act on S protein to block this process and kill the virus in the early stage of its life cycle. In addition, nanoparticles such as Ag, Au, and Cu supported by photocatalysts or ozone catalysts (fig. 1) can not only catalyze the generation of free radicals to attack viruses, but also release toxic ions to act on viruses to achieve synergistic killing of viruses.
3.2.2 Other Metal Nanomaterials Ion Release Disinfection Technology
In addition to silver and gold nanoparticles, polymer modified or coated metal nanoparticles (such as copper nanoparticles) achieve the purpose of targeted disinfection by controlling the release of metal ions. At the same time, these nanoparticles can synergistically enhance the virus-killing effect when combined with typical antiviral drugs. For example, masks impregnated with copper oxide can safely reduce the risk of environmental contamination of influenza viruses without changing the filtering capacity of masks[133]. In 2017, polyurethane/CuO nanocomposites were successfully developed as effective antibacterial filters for air purification[134]. In addition, the combination of copper nanoparticles (CuNPs) as the core and benzalkonium chloride (BAC, an asymmetric alkylammonium salt) as the shell to prepare antiviral nanoparticles with core-shell structure (CuNPs @ BAC) can synergistically enhance the antibacterial and antiviral efficacy[135]. In addition, metal nanomaterials can also be used in conjunction with drugs suitable for the treatment of COVID-19. For example, chloroquine (CQ) and hydroxychloroquine (HCQ) have been shown to play an important role in the treatment of SARS-CoV-2 infection. Both of them belong to the aminoquinoline class of drugs and have a heterocyclic skeleton structure of amino, so they can form metal complexes with transition metals such as Fe (II), Ni (II), Zn (II) and Cu (I)[50]. Therefore, CQ and HCQ can be used for functionalizing and modifying the metal nanoparticle material with high biocompatibility, and the metal nanoparticle material is used as a drug carrier to enter the body of a patient, so that the SARS-CoV-2 virus can be efficiently killed by releasing metal ions for disinfection and cooperating with an antiviral drug.
In addition, the mechanism of sustained-release disinfection through the release of ions from nanomaterials has also been widely concerned by researchers. It has been confirmed that the viability of SARS-CoV-2 is different under different environmental conditions (aerosol, plastic, stainless steel, copper and cardboard), copper can inactivate the virus in a shorter time, and the rate of inactivation is proportional to the content of copper, the release of copper ions and mediated production of ROS are the causes of virus inactivation[2]. It is also found that the controlled release of Cu2+ is the key to regulate the inactivation performance of antibacterial agents and antiviral agents. Therefore, the supported copper nanoparticles can be used as ion slow-release agents to control the release of active ions to regulate the virus inactivation behavior, thereby achieving long-term inhibition of the virus. At present, researchers at Copptech in Chile have developed loaded copper nanomaterials that can effectively curb the spread of SARS-CoV-2 virus, which can block the spread of COVID-19 by coating public transport, airports, hospitals, schools and other infrastructure with varnish containing copper nanoparticles[136]. Due to the slow release mechanism of nanomaterials, the antibacterial and antiviral properties of these facilities can be maintained for ten years or even longer.
3.3 Nano material structure effect and disinfection application
Nanomaterials can also use their unique nanostructure effects to kill pathogens through physical action. This kind of structural effect includes the puncture effect of nanotubes and the cutting effect of nanosheets, surface charge and surface tension effects[137]. Among them, carbon nanomaterials, especially carbon nanotubes (CNTs) and graphene, have been extensively studied and found to be effective in killing or harming pathogenic microorganisms[138,139].
Carbon nanotubes (CNTs), including single-walled carbon nanotubes (SWCNTs) and multi-walled carbon nanotubes (MWCNTs), are a typical class of carbon-based nanomaterials. As a kind of one-dimensional tubular material with special structure, it has unique structural characteristics. Due to their small diameter and highly stable carbon skeletons, carbon nanotubes can directly penetrate into pathogenic bacteria containing cellular structures.It was found that carbon nanotube materials have good killing effect on bacteria, fungi and other microorganisms, and the following mechanisms were proposed: (1) Carbon nanotubes can directly and mechanically destroy the metabolic pathways in cells[70,140,141]; (2) Carbon nanotubes can induce oxidative stress in cells; (3) Carbon nanotubes can directly and physically damage cell membranes. The number of layers of carbon nanotubes will lead to the difference of antibacterial ability. It is found that the antibacterial ability of SWCNTs is significantly higher than that of MWCNTs. The mechanism is as follows: (1) Compared with MWCNTs, SWCNTs have smaller nanotube diameter, which is conducive to the segmentation and partial penetration of nanotubes on the cell wall[142]; (2) the larger surface area of SWCNTs is available for contact and interaction with the cell surface; (3) The unique chemical and electronic characteristics of SWCNTs[142]. In addition, metal-based nanotubes, such as titanate nanotubes, which have been widely studied in recent years, also have foreseeable application prospects in the killing of COVID-19 because of their extremely stable "rigid" skeleton structure, thin tube diameter and thin tube wall, and photocatalytic activity[143⇓~145].
Graphene is a two-dimensional crystalline carbon material with a single atomic layer thickness, which has potential applications in the fields of biomedicine and disinfection due to its unique lamellar structure, large specific surface area and good stability[141,146]. Graphene and its derivative materials have been proved to have good antibacterial effect[147]. The antibacterial mechanism of graphene suggests that its unique sheet structure is the main source of its antibacterial performance, and the sharp edge structure of graphene material can play the role of "nano-blade", which directly damages the cell membrane surface mechanically (the physical effect shown in Figure 1C)[148]. Previous studies have also reported that the efflux of intracellular substances can be directly observed after the interaction of graphene with bacteria[149⇓~151]. It is also found that the structure of graphene has a significant effect on its antibacterial properties. The first is the size of the graphene sheet, which can enhance the adsorption capacity of graphene and make it easier to adsorb on the surface of the cell membrane, so as to improve the antibacterial ability[152]. On the other hand, when the size of graphene is reduced, it is easier for graphene to penetrate the phospholipid bilayer on the biological surface, and the reduction of the size can induce the defect structure on the surface of graphene and enhance its antibacterial activity[139,151]. Secondly, the number of layers of graphene-based materials will also have an impact on their antibacterial ability: some studies suggest that graphene-based materials with fewer layers can improve their antibacterial activity by improving the ability to destroy cell membranes[153]; However, some studies have put forward the opposite conclusion that the increase of the number of layers can achieve the antibacterial effect more effectively. At present, there is no definite conclusion about the number of layers of graphene-based nanomaterials and their antibacterial and disinfection properties, and further research is needed[154]. The lamellar cutting effect of nano-graphene is a unique feature of nanomaterials, which is a significant manifestation of its nanostructure effect.
In addition, it has been confirmed that the unique surface properties of nanomaterials also have inhibitory effects on viruses. The experimental results have shown that the sharp edge surface and negative charge of graphene oxide can effectively inhibit PRV and PEDV[151]. In the process of killing the H9N2 virus by the graphene oxide as shown in fig. 11, firstly, the graphene can capture the virus through adsorption or static electricity by using its large specific surface area, and then the captured virus will be damaged by the graphene and the surface protein will be gradually inactivated, so as to achieve the purpose of inactivating the virus[155]. Other studies have found that graphene can directly interact with proteins or peptides through π-π bond interaction or hydrophobicity, and graphene oxide can stack peptides on its surface through electrostatic interaction and hydrophobicity.This also proves that graphene oxide has a good capture effect on viruses, which provides a theoretical basis for the application of SARS-CoV-2 virus[156][157]. It has been confirmed that graphene-based materials can adsorb HIV viral proteins and significantly reduce the toxicity of the virus to cells[158]. Scholars in related fields have also pointed out that the special structural properties and surface effects of graphene, together with virus affinity and light and heat treatment, also have high applicability in the inhibition and inactivation of novel coronavirus SARS-CoV-2[159].
4 Conclusion and prospect
Because the novel coronavirus SARS-CoV-2 has a certain stability in water, urban sewage and medical wastewater are not only the "sink" of virus concentration, but also the "source" of release to the water environment due to incomplete treatment. Although the traditional sewage disinfection process can inactivate the virus to a certain extent, considering the high transmission and pathogenicity of COVID-19, more stringent and efficient disinfection technology and process need to be expanded. Nanomaterials have high specific surface area, high surface energy, unique nano-size structure and excellent physical and chemical properties, which make nanotechnology show special advantages in the killing of COVID-19. At present, nanomaterial photocatalysis and nanoparticle toxic ion release technology have been successfully applied to the inactivation of SARS-CoV-2, and the existing virus inactivation research and practice also show that environmental nanotechnology can be applied to the inactivation of novel coronavirus in water, so as to block its secondary transmission in the water environment. In the future, there are still the following scientific problems and engineering strategies to be considered in this field.
(1) In the aspect of nano-photocatalysis, attention should be paid to the development of photocatalyst materials that can be driven by sunlight, so as to achieve efficient utilization of energy and significant reduction of technical costs, and the materials can also be used quickly and conveniently; And an application scheme of that photocatalysis material driven by sunlight in an open environment (such as an open wat body) is formed.
(2) At present, there are few studies on heterogeneous catalytic addition of nanomaterials for advanced oxidation disinfection. Considering the broad-spectrum disinfection effect, high selectivity and applicability of SO4·-, nanomaterials and corresponding supporting technologies that can efficiently stimulate the production of SO4·- should be developed in the future.
(3) In the aspect of ozone disinfection catalyzed by nanomaterials, specific ozone nanomaterials were developed to promote indirect oxidation and improve the efficiency of ozone disinfection process. At the same time, a portable immobilized material ozone catalytic device was developed to provide guarantee for the emergency disposal of the epidemic.
(4) Develop coupling heterogeneous advanced oxidation processes, such as photocatalytic synergetic Fenton reaction, photocatalytic coupling persulfate system, photocatalytic ozone system, etc., so as to improve the generation efficiency and yield of ROS and achieve efficient killing of viruses.
And (5) the novel coronavirus resisting drug and the functionalized nano material are compounded to form a hybrid material, and the hybrid material generates free radicals and synergizes with the high efficiency of the drug under the conditions of illumination, oxidant or ozone, so as to greatly improve the inactivation capability of the novel coronavirus.
(6) Aiming at actual domestic sewage treatment plants and hospital wastewater treatment projects, develop integrated sewage treatment technologies and equipment that can synchronously degrade pollutants and viruses to meet the needs of sewage treatment in special situations (such as designated isolation areas and hospitals) and ensure zero risk of water-borne COVID-19 transmission. At the same time, attention should be paid to the spread of viruses at the water-air interface in the process of water treatment, and the equipment developed should be used to cut off the possible spread of viruses into the air.
(7) Considering the characteristics of nanomaterials, such as strong migration, high dispersion and difficult recovery of powder materials after use, priority should be given to the development and application of immobilized material mode equipment for practical engineering.
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