key: cord-1053605-gyj6cyku
authors: Saadatpour, Fatemeh; Mohammadipanah, Fatemeh
title: Physicochemical susceptibility of SARS‐CoV‐2 to disinfection and physical approach of prophylaxis
date: 2020-12-02
journal: Health Sci Rep
DOI: 10.1002/hsr2.213
sha: 1065f4769c410b7fa7a60acbe3e59e4b7b42047d
doc_id: 1053605
cord_uid: gyj6cyku

The transmission control of the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is the most effective strategy by the absence of its specified vaccine or drug. Although the aerosol mediated transmission of SARS‐CoV‐2 has been confirmed, the physicochemical treatment of the biotic and abiotic objects is still the most promising approach in its infection control. The front line of the most effective disinfecting compounds on SARS‐CoV‐2 implies to be sodium hypochlorite, ethanol, hydrogen peroxide, quaternary ammonium compounds, and phenolic compounds, respectively. However, widely used compounds of alkyldimethylbenzylammonium chloride (benzalkonium chloride) biguanides (chlorhexidine) have not shown the multitude load reduction in less than 10 minutes. The susceptibility of SARS‐CoV‐2 to physical treatment follows the pattern of heat, acidity, and UV radiation. Rather all of the mentioned physical or chemical treatments, target the envelope proteins of the coronavirus mainly by impairing its entry to host cells. The anti‐SARS‐CoV‐2 activity of combinatorial physicochemical treatments or evaluation of new chemical entities or physical treatments such as microwave irradiation still needs to be explored. Therefore, the development of a reliable decontamination protocol for SARS‐CoV‐2 demands revealing its stability pattern study vs a spectrum of single and combinatorial physicochemical parameters.

skin and surfaces are preferred to be followed in the clinic and society. 3 Confining the spread of the virus can minimize the risk of human infection and the environmental toxicity associated with long-term usage of disinfectants in the upcoming months of lacking the vaccine or drugs of SARS-CoV-2.

Since the beginning of the pandemic, several reports have been published on disinfectants affecting coronaviruses, and a systematic review on the physicochemical susceptibility of the SARS-CoV-2 was targeted in this review. In this paper, in addition to summarizing the available information in the field of disinfectants and physical treatments on SARS-CoV-1, MERS-CoV, and SARS-CoV-2, a hierarchical categorization is presented based on the effective contact time and the virus titer reduction. This classification appears to be useful in selecting effective disinfectants for effective prophylaxis of virus dissemination.

This study summarizes the effectiveness of the physical and chemical agents in reducing the stability and infection of human coronavirus published so far to recommend a balanced prophylaxis protocol for SARS-COV-2.

Coronaviruses are classified in the subfamily Orthocoronavirinae from the family Coronaviridae, in the order Nidovirales as + ssRNA enveloped virus. 4 Although most of the H-CoVs) cause typically mild respiratory tract infections and the common cold in humans, the nonhuman adapted forms (SARS-CoV, MERS-CoV, SARS-CoV-2) are pathogenic. 5 A high tropism to the respiratory tract cells is observed by SARS-CoV-2, which leads to severe sometimes irreversible lung injury by colonization in these cells and eventually acute respiratory syndrome.

Binding to specific receptor (the angiotensin-converting enzyme 2) together with proteolytic activation of spike protein in the presence of endosomal low pH is among the important factors that allow the attachment of the SARS-CoV-2 fusion peptide into target cell membranes. Therefore, the coating structures involved in attachment and entry in the initial stage of infection are the pivotal targets of antiviral drug discovery efforts for SARS-CoV-2. 6 

The causative agent of SARS-CoV-2 seems to be spreading sustainably to all countries soon. It has been found that there is a direct relationship between population density in public places, transportation, and SARS-CoV-2 distribution pattern. The indirect SARS-CoV-2 transmission occurs through the release of the virus from an infected person to the skin or surfaces, and eventually to the next person's mucous membranes (eyes, nose, or mouth). 7 Furthermore, a study in China demonstrates coherency between the SARS-CoV-2 contagion rate and the type of vehicle used for transportation by 68.72% and 11.85% of infection transmission when trafficking by train and car, respectively. 8 The main way of coronaviruses spread is a person-toperson transmission with the incubation times between 1 and 14 days, which occurs in direct and indirect contacts or via respiratory droplets. 9 Based on previous evidence, the transmission of H-CoVs and presumably SARS-CoV-2 is influenced by parameters such as flow and density of the population, immunity of the human host, climate variations like high temperature and higher relative, or absolute humidity. 10, 11 Investigation of globally meteorological conditions also indicates that calm, cold, dry, and overcast conditions can be favorable to the SARA-CoV-2 transmission. 10 

Due to the high genetic similarity of SARS-CoV-2 with SARS-CoV-1 and MERS-CoV, 12 physical treatments for other members of its own family are expected to have a similar effect on SARS-CoV-2. Although, it is generally deduced that coronavirus strains have a limited tolerance and survival capacity on dry surfaces. Nevertheless, some studies confirmed that the strains with high pathogenicity, SARS-CoV-1, SARS-CoV-2, and MERS-CoV remain infectious in drought conditions ranging from 2 hours to 28 days dependent on the type of surfaces and relative humidity (RH) on different nonbiologic materials at room temperature (RT). 13, 14 In principle, H-CoVs have the potential to retain their infectivity in various environmental reservoirs like surface water and untreated water, food materials, sewage and in general, on a wide range of biological and nonbiological materials, including many types of smooth and porous materials such as metals, woven, paper, ceramic, wood, glass, formica, tiles tissue, and feathers. 15 A new investigation reported that the SARS-CoV-2 can remain viable on paper and tissue paper, air, copper, cloth and wood, cardboard, and plastic for up to 30 minutes, 3, 4, 24, and 72 hours, respectively. 14,16 By contrast, SARS-CoV-2 is more stable on smooth surfaces such as plastics and stainless steel (for 4 days) and Banknote (for 2 days). Notably, SARS-CoV-2 can be infective on the inner and outer layer of face mask up to 4 and 7 days, respectively. 14 In addition to the intrinsic nature of the surfaces some other critical factors including, strain variations, imposed titer, temperature, pH, irradiation, and humidity influence the persistence and survival of H-CoVs. 13 In general, H-CoVs are more resistant to ambient humidity and acidity than to heat treatment and UV radiation ( Figure 1 ). The decrease in temperature coupled with the increase in RH support the coronavirus infectivity for a longer time. 17 Although, the survival of this viral group, and especially SARS-CoV-2, generally decreases at temperatures of 30 C to 40 C, they can remain viable and infective for up to 28 days at temperatures around 4 C to 20 C. 18 The HCoV-229E persists significantly longer in 50% RH compared to the 30% humidity at RT. Also, the reported survival times for SARS-CoV-1 vary between 1 day (80%-95% RH at 33 C) and 28 days (40%-50% RH at RT). 19 Similarly, Bu et al reported that SARS-CoV-2 can maintain its transmissibility and infectivity from 13 C to 19 C in humidity of 50% to 80% for 1 to 7 days dependent on the material of virus-infected surfaces. 20 Recently, chin et al showed that only a 0Á7 log 10 reduction of virus infectious titer was observed after 14 days incubation at 4 C. 14 

The skin contamination may occur by direct contact with patient secretions or indirectly from contact with the high-touch surfaces that have become contaminated with dispersed droplets. The exact surviving time of H-CoVs on human skin is still not specifically determined but it can stay long enough to spread from person to person. 23 There is a limited study on the virucidal antiseptics of SARS-CoV-2 and most available data only origin SARS-CoV-1 and H-CoV 229E ( Table 1 ).

The denaturing and coagulation effect of alcohols on proteins makes them effective against a wide range of bacteria and viruses. As investigated in numerous studies, alcohols have demonstrated immediate, significant inhibitory effects against the majority of enveloped and nonenveloped viruses including the members of coronaviruses family. 33 Alcohol-based hand sanitizers are widely considered to be effective to reduce or eliminate infectious microorganism, bacterial/ viral load. Common alcoholic disinfectants such as ethanol, isopropanol, and n-propanol are applied in the form of hand rub rinses, gels, and foams. It has been confirmed that ethyl alcohol diminishes the infectivity of coronavirus at concentrations of 78% to 95% within 30 seconds contact time by greater than 4.0 log 10 . 26 Additionally, WHO reports that alcohol-based formulations (80% ethanol or 75% 2-propanol) have completely inactivated SARS-CoV-1 and MERS-CoV in suspension tests after 30 seconds of exposure time. 25 Moreover, a recent study has shown that >30% concentrations of ethanol and isopropanol were effective in inactivating SARS-CoV-2 within 30 seconds. 28 Among the compounds based on halogens, povidoneiodine (PVP-I) is widely available for medical and personal use. Based on the data obtained by quantitative assay, this compound shown rapid and effective virucidal activity against SARSCoV-2 corresponding to ≥4 log 10 reduction of virus titer, within 30 seconds of contact in all concentrations of 0.45%,1%, 7.5%, and 10%. 31 Undoubtedly, the use of these compounds as antiseptics can augment health and hygiene measures to limit the COVID-19 separating in the community.

Among all conventional prophylaxis approaches, using surface disinfectants is one of the effective approaches for reducing the risk of exposure to SARS-CoV-2; although, its airborne nature is plausible.

Therefore, one of the most drastic approaches that interrupt the coronaviruses and in particular, SARS-CoV-2 infection, is the tailored, F I G U R E 1 Stability trend of the virus exposed to physicochemical stress is indicated by fading the color intensity of the virus. As shown, the detergents and disinfectants are the most detrimental treatments for SARS-CoV-2. In contrast, exposure to physical treatment has less efficiency in reducing the viral infectivity. Many members of the coronavirus can survive for 7 to 28 days at the low relative humidity (20%-40%) and dry conditions at room temperature (20 C-21 C). They are also resistant to a wide range of pH changes (3) (4) (5) (6) (7) (8) (9) (10) (11) (12) . While, increasing the temperature to 75 C reduces the viral load to ≥5 log 10 in less than 10 minutes. The viral particles of SARS-CoV-2 become undetectable in less than 10 minutes at 4016 μW/cm 2 of UV radiation 44 suitable, and periodical disinfection of contaminated surfaces and equipment.

Although it is shown that enveloped viruses are in general more sensitive to the disinfectants than the nonenveloped viruses, coronavirus exhibit resistance to some conventional chemical disinfectants. 34 The human coronaviruses, including HCoV-229E and SARS-CoV-1, as well as several animal coronaviruses (e.g., mouse hepatitis virus and transmissible gastroenteritis virus of pigs), have been used as coronavirus models to investigate and determine the activity of chemical disinfectants. As a result, among the candidates of formulated disinfectants against coronaviruses, just some of them have received the Environmental Protection Agency (EPA) confirmation. 35 In general, biocidal agents can be categorized in the nine groups including, acids, alcohols, oxidizing agents, aldehydes, phenols, alkalis, biguanides, halogens, and quaternary ammonium compounds, among which, hydrogen peroxide, alcohols, sodium hypochlorite, benzalkonium chloride, or biguanides are commonly used to disinfect the virus exposed suspected area, mainly in healthcare settings. 36 The virucidal activities of different disinfectants based on the so far investigations are summarized in Table 2 

Unlike many enveloped viruses that are sensitive to most of the physicochemical changes, less susceptibility of H-CoVs to these changes has been demonstrated in some studies. 42 The majority of the physical treatments similar to chemical interventions agents inactivate the viruses via denaturation of its structural proteins and interference with the virus and host cell-effective interaction. 22 A thermal disinfection program can be variable from 60 C, 65 C or 80 C, for 30, 15 and 1 minute, respectively. All of these schedules were efficacious to decrease the infectivity of H-CoVs up to four logarithmic reductions. 43 Two H-CoVs, SARS-CoV-1 and MERS-CoV, can be completely inactivated at 65 C and 75 C after 15 minutes, respectively. 44, 45 It is confirmed that inactivation of SARS-CoV-2 can be achieved after 5 minutes with the incubation temperature increased to 70 C. 46 The N protein of SARS-CoV-1 is substantially denatured at 55 C treatment for 10 minutes. 43 Also, it is suggested that extreme pH conditions can probably change the infectious nature of the viral particles and indirectly affect the attachment and fusion process of spike proteins to cell membranes. The alkaline (pH > 12) and acidic (pH <3) conditions can cause the inactivation of SARS-CoV-1 at 37 C while the viral articles remain infectious in pH range of 5 to 9. The optimum UV range for uppermost disinfection efficacy is between 245 and 285 nm.

The complete deactivation effect of UV irradiation for a 6 minutes is reported for SARS-CoV-1 at 60 minutes at >90 μW/cm 2 . 19, 41 As a similar susceptibility is assumed for SARS-CoV-2, it is recommended to use the UV radiation treatment in the compatible area to confine the environmental discharge of the chemical disinfectants (Table 3 ).

The highly infectious nature of SARS-CoV-2 has triggered an urge to investigating its susceptibility, transmissibility, and persistence, to Based on studies conducted till August 2020, the effective ingredients to H-CoVs titer reduction can be graded based on Figure The average of D90 values (UV energy that inactivates 90% of the exposed virus) for different strains of coronaviruses is 308 J/m 2 .

Although this dose has not yet been determined for SARS-CoV-2, similar stability is expected. The surface cleaning precedent to the disinfectants such as sodium hypochlorite 0.2% and hydrogen peroxide 0.5%, followed by UV-irradiation, is assumed to completely inactivate this group of infectious viruses including SARS-CoV-2. In addition, physical stress of acidic pH created by many of the EPA-approved chemical antiviral reagents can have a synergistic effect with chemical reagents on inactivation of viral particles. 55 In contrary, the acidity condition may lead to neutralization of the antiviral compound or even the production of toxic byproducts.

As described in case of most viruses, the major inactivation mechanism by heat treatment is the denaturation of surface glycoproteins of enveloped viruses. As a result, host cell receptordetecting structures are out of reach by the virus, which reduce its infectivity. This magnified survival rate at low temperature may explain the winter propagation of coronaviruses and also the tropism of the virus to the respiratory system. Breathing cold air in winter may diminish the lung temperatures up to 5 C. 56 Since the bronchus is fully saturated with water vapor, these conditions provide an appropriate situation for coronaviruses viability and infection development. According to a recent study, it is demonstrated that SARS-CoV-2 can be detected in aerosols for up to 3 hours. This implies that treatments targeting airborne transmissions such as using UV radiation or the ozone gas must be more emphasized in parallel to the disinfection regimes. 16 In forthcoming studies, the prioritization must be allotted to the survival time of the virus, which dramatically influences the probabilistic of the transmission. In contrast, the load reduction is more corre- SARS-CoV-2 may also deliver some new potential effective compounds.

The power unit and time necessary to inactivate the virus by microwave radiation or ozone vapor are also demanding to be described.

Furthermore, in such a massive worldwide usage of the disinfectants, the vast discharge and waste of these chemicals to the environment must have also be foreseen. At least, two types of studies can ameliorate this massive scale of chemical waste concern. The lines of studies that can diminish the required concentration or replace them with less toxic alternatives or the ones that introduce the decontamination and neutralization of these chemicals in discharged waste to the nature.

Authors would like to thank the support of Science and Technology

Park of the University of Tehran (UTSTP). Funding is not applicable for the paper.

The authors declare no conflict of interest for the content of the paper.

Data collection and writing original draft: Fatemeh Saadatpour.

Conceptualization, data collection, review, and editing: Fatemeh

Mohammadipanah.

All authors have read and approved the final version of the manuscript.

The corresponding author had full access to all of the data in this study and takes complete responsibility for the integrity of the data and the accuracy of the data analysis.

The authors declare that this manuscript is an accurate and transparent comparative overview of the published literature on the subject.

All the data reported in this manuscript are derived from published articles.

Fatemeh Mohammadipanah https://orcid.org/0000-0003-0286-5342

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How to cite this article: Saadatpour F, Mohammadipanah F. Physicochemical susceptibility of SARS-CoV-2 to disinfection and physical approach of prophylaxis