key: cord-0720958-jst4ghhb
authors: Ijaz, M. Khalid; Nims, Raymond W.; Whitehead, Kelly; Srinivasan, Vanita; Charlesworth, Bruce; McKinney, Julie; Rubino, Joseph R.; Ripley, Mark; Jones, Chris
title: Microbicidal Actives with Virucidal Efficacy against SARS-CoV-2
date: 2020-05-24
journal: Am J Infect Control
DOI: 10.1016/j.ajic.2020.05.015
sha: beacdeb29f411f4d2e25efb82336167bbb2e9b27
doc_id: 720958
cord_uid: jst4ghhb

nan

Given the practical importance of microbicides having efficacy against SARS-CoV-2 in home, community, and healthcare settings, we report evidence of the virucidal efficacy of a number of formulated microbicidal actives against SARS-CoV-2, as evaluated per ASTM International 1, 2 and EN 3 standards.

Dissemination of SARS-CoV-2 from infected to susceptible individuals is believed to occur directly, via respiratory droplets and droplet nuclei/aerosols, and indirectly through contaminated high-touch environmental surfaces (HITES). 4 SARS-CoV-2 has been reported to remain infectious on contaminated HITES for hours to days, 5 allowing for onward self-infection of new individuals when contaminated hands come into contact with susceptible tissues (mucous membranes of the nose, eyes, and mouth). This Droplets-HITES-Hands nexus 6 is central to the chain of infection with SARS-CoV-2, and highlights the critical role that targeted application of effective microbicides against potentially contaminated HITES and hands plays in infection prevention and control (IPAC) during the ongoing COVID-19 pandemic.

Fortunately, enveloped viruses such as SARS-CoV-2 are among the most susceptible of pathogens to formulated microbicidal actives and detergents (including personal care soaps and liquid hand washes). 7, 8 Inactivation of such viruses by formulated microbicidal actives and detergents is believed to occur as a result of disruption of the virally modified, host-cell-derived, phospholipid bilayer glycoproteinaceous envelope and the associated spike glycoproteins that interact with the angiotensin-converting enzyme (ACE2) receptor required for infection of host cells. 8 Virucidal efficacy of a selection of formulated microbicidal actives against SARS-CoV-2 has, to date, been assumed based on efficacy data obtained using other coronaviruses 8, 9 or, as reported recently, 5 based on non-standardized methods of assessing viral inactivation (i.e., log 10 reduction in infectious titer) in suspension without details of the testing method used including appropriate controls. To date, virucidal activity against SARS-CoV-2 has not been demonstrated definitively through testing conducted per standardized surface 2 and suspension 1, 3 methodologies. In Table 1 , we provide definitive evidence of efficacy for inactivation of SARS-CoV-2, on contaminated prototypic HITES and suspensions, of products formulated with the following microbicidal actives: ethyl alcohol; para-chloro-meta-xylenol (PCMX); salicylic acid; and quaternary ammonium compounds. All of the microbicidal actives were effective for inactivating SARS-CoV-2, demonstrating ≥3.0 to ≥4.7 log 10 reduction of infectious virus within the tested 1 to 5 minutes contact time in virucidal efficacy testing conducted per applicable ASTM International and EN standards. 

Standard practice to assess the activity of microbicides against viruses in suspension

Standard practice to assess virucidal activity of chemicals intended for disinfection of inanimate, nonporous environmental surfaces

Chemical disinfectants and antiseptics. Quantitative suspension test for the evaluation of virucidal activity in the medical area

Modes of transmission of virus causing COVID-19: implications for IPC precaution recommendations

Stability of SARS-CoV-2 in different environmental conditions

Generic aspects of the airborne spread of human pathogens indoor and emerging air decontamination technologies

Should test methods for disinfectants use vertebrate virus dried on carriers to advance virucidal claims?

Combating SARS-CoV-2: leveraging microbicidal experiences with other emerging/re-emerging viruses

Persistence of coronaviruses on inanimate surfaces and its inactivation with biocidal agents

*Abbreviations used: FBS, fetal bovine serum; PCMX, para-chloro-meta-xylenol; QAC, quaternary ammonium compound; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2 (isolate USA-WA1/2020, obtained from CDC through BRI Resources), w/v, weight to volume; w/w, weight to weight. The test cells were Vero E6, an African green monkey kidney cell obtained from American Type Culture Collection (ATCC CRL-1586). The growth medium was minimal essential medium supplemented with 5% FBS, L-glutamine, and antibiotics. †Tested using EN 14476:2013+A2:2019 methodology 3 ‡Tested using ASTM E1052-20 methodology 1 §Alkyl dimethyl benzyl ammonium chloride (C12-16)|Where multiple values are displayed, this reflects the testing of multiple independent lots of the formulated microbicidal actives. ¶Alkyl (50% C14, 40% C12, 10% C16) dimethyl benzyl ammonium chloride # Alkyl (50% C14, 40% C12, 10% C16) dimethyl benzyl ammonium saccharinate To our knowledge, this is the first report of the virucidal efficacy of formulated microbicidal actives, determined using industry/regulatory-relevant global standardized (ASTM International, EN) methodologies, for inactivating SARS-CoV-2. Products formulated with the microbicidal actives studied here should be useful for healthcare workers, researchers, and the public at large as critical interventions for IPAC of SARS-CoV-2 and the ongoing COVID-19 pandemic.