Microbicidal actives with virucidal efficacy against SARS-CoV-2

Abstract

Given the practical importance of microbicides having efficacy against SARS-CoV-2 in home, community, and health care settings, we report evidence of the virucidal efficacy of a number of formulated microbicidal actives against SARS-CoV-2, as evaluated per ASTM International1ASTM International. ASTM E1052-20. Standard practice to assess the activity of microbicides against viruses in suspension. 2020; Available at: https://www.astm.org/Standards/E1052.htm. Accessed May 7, 2020.Google Scholar,2ASTM International. ASTM E1053-20. Standard practice to assess virucidal activity of chemicals intended for disinfection of inanimate, nonporous environmental surfaces. 2020; Available at: https://www.astm.org/Standards/E1053.htm. Accessed May 7, 2020Google Scholar and EN3British Standards Institute. BS EN 14476:2013+A2:2019. Chemical disinfectants and antiseptics. Quantitative suspension test for the evaluation of virucidal activity in the medical area. Test method and requirements (Phase 2/Step 1). 2019; Available at: https://infostore.saiglobal.com/en-us/Standards/BS-EN-14476-2013-A2-2019-238423_SAIG_BSI_BSI_2753744/. Accessed May 7, 2020Google Scholar 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).4World Health Organization. Modes of transmission of virus causing COVID-19: implications for IPC precaution recommendations. 2020; Available at:https://www.who.int/news-room/commentaries/detail/modes-of-transmission-of-virus-causing-covid-19-implications-for-ipc-precaution-recommendations. Accessed May 7, 2020Google Scholar SARS-CoV-2 has been reported to remain infectious on contaminated HITES for hours to days,5Chin AWH Chu JTS Perera MRA et al.Stability of SARS-CoV-2 in different environmental conditions.Lancet Microbe. 2020; 1: e10Abstract Full Text Full Text PDF PubMed Scopus (1155) Google Scholar 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 nexus6Ijaz MK Zargar B Wright KE Rubino JR Sattar SA Generic aspects of the airborne spread of human pathogens indoor and emerging air decontamination technologies.Am J Inf Control. 2016; 44: S95-S101PubMed Google Scholar 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 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).7Ijaz MK Rubino JR. Should test methods for disinfectants use vertebrate virus dried on carriers to advance virucidal claims?.Inf Control Hosp Epidemiol. 2008; 29: 192-194Crossref PubMed Scopus (16) Google Scholar,8Ijaz MK Sattar SA Rubino JR Nims RW Gerba CP Combating SARS-CoV-2: leveraging microbicidal experiences with other emerging/re-emerging viruses. [e-pub ahead of print].OSF Preprints. 2020; (Accessed June 9, 2020)https://doi.org/10.31219/osf.io/wjzuqCrossref Google Scholar 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 receptor required for infection of host cells.8Ijaz MK Sattar SA Rubino JR Nims RW Gerba CP Combating SARS-CoV-2: leveraging microbicidal experiences with other emerging/re-emerging viruses. [e-pub ahead of print].OSF Preprints. 2020; (Accessed June 9, 2020)https://doi.org/10.31219/osf.io/wjzuqCrossref Google Scholar 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 coronaviruses8Ijaz MK Sattar SA Rubino JR Nims RW Gerba CP Combating SARS-CoV-2: leveraging microbicidal experiences with other emerging/re-emerging viruses. [e-pub ahead of print].OSF Preprints. 2020; (Accessed June 9, 2020)https://doi.org/10.31219/osf.io/wjzuqCrossref Google Scholar,9Kampf G Todt D Pfaender S Steinmann E Persistence of coronaviruses on inanimate surfaces and its inactivation with biocidal agents.J Hosp Inf. 2020; 104: 246-251Abstract Full Text Full Text PDF PubMed Scopus (2495) Google Scholar or, as reported recently,5Chin AWH Chu JTS Perera MRA et al.Stability of SARS-CoV-2 in different environmental conditions.Lancet Microbe. 2020; 1: e10Abstract Full Text Full Text PDF PubMed Scopus (1155) Google Scholar based on nonstandardized methods of assessing viral inactivation (ie, log10 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 surface2ASTM International. ASTM E1053-20. Standard practice to assess virucidal activity of chemicals intended for disinfection of inanimate, nonporous environmental surfaces. 2020; Available at: https://www.astm.org/Standards/E1053.htm. Accessed May 7, 2020Google Scholar and suspension1ASTM International. ASTM E1052-20. Standard practice to assess the activity of microbicides against viruses in suspension. 2020; Available at: https://www.astm.org/Standards/E1052.htm. Accessed May 7, 2020.Google Scholar,3British Standards Institute. BS EN 14476:2013+A2:2019. Chemical disinfectants and antiseptics. Quantitative suspension test for the evaluation of virucidal activity in the medical area. Test method and requirements (Phase 2/Step 1). 2019; Available at: https://infostore.saiglobal.com/en-us/Standards/BS-EN-14476-2013-A2-2019-238423_SAIG_BSI_BSI_2753744/. Accessed May 7, 2020Google Scholar 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, salicylic acid, and quaternary ammonium compounds. All of the microbicidal actives were effective for inactivating SARS-CoV-2, demonstrating ≥3.0 to ≥4.7 log10 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.Table 1Virucidal efficacy of formulated microbicidal actives against SARS-CoV-2*Virucidal efficacy testing was conducted by Microbac Laboratories, Inc (Sterling, VA). 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.Product typeActive ingredient concentrationTemperature(°C)Contact time (minutes)Log10 reduction in infectious SARS-CoV-2 titer achievedIn productTestedTested per ASTM E1052-20 or EN 14476:2013+A2:2019 on SARS-CoV-2 in suspension studies with a 5% FBS organic loadAntiseptic liquid†Tested using EN 14476:2013+A2:2019 methodology.34.7% w/v0.094% w/v PCMX (tested at 1:50 of supplied)215≥4.7Hand sanitizer gel†Tested using EN 14476:2013+A2:2019 methodology.361% w/w49% w/w ethanol (tested at 1:1.25 of supplied)211≥4.2Liquid hand wash‡Tested using ASTM E1052-20 methodology.10.10% w/w0.025% w/w salicylic acid (tested at 1:4 of supplied)371≥3.1Bar soap‡Tested using ASTM E1052-20 methodology.10.11% w/w0.018% w/w PCMX (tested at 1:6.25 of supplied)381≥3.0Surface cleanser†Tested using EN 14476:2013+A2:2019 methodology.30.096% w/w0.077% w/w QAC§Alkyl dimethyl benzyl ammonium chloride (C12-16). (tested at 1:1.25 of supplied)215≥4.1Tested per ASTM E1053-20 on SARS-CoV-2 dried on a glass surface with a 5% FBS organic loadDisinfectant wipes|Where multiple values are displayed, this reflects the testing of multiple independent lots of the formulated microbicidal actives.0.19% w/w0.19% w/w QAC¶Alkyl (50% C14, 40% C12, 10% C16) dimethyl benzyl ammonium chloride. (tested as supplied)212≥3.5, ≥3.5, ≥3.5Disinfectant spray|Where multiple values are displayed, this reflects the testing of multiple independent lots of the formulated microbicidal actives.50% w/w ethanol 0.083% w/w QAC50% w/w ethanol 0.083% w/w QAC#Alkyl (50% C14, 40% C12, 10% C16) dimethyl benzyl ammonium saccharinate. (tested as supplied)212≥4.6, ≥4.7, ≥4.5FBS, 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. Virucidal efficacy testing was conducted by Microbac Laboratories, Inc (Sterling, VA). 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.3British Standards Institute. BS EN 14476:2013+A2:2019. Chemical disinfectants and antiseptics. Quantitative suspension test for the evaluation of virucidal activity in the medical area. Test method and requirements (Phase 2/Step 1). 2019; Available at: https://infostore.saiglobal.com/en-us/Standards/BS-EN-14476-2013-A2-2019-238423_SAIG_BSI_BSI_2753744/. Accessed May 7, 2020Google Scholar‡ Tested using ASTM E1052-20 methodology.1ASTM International. ASTM E1052-20. Standard practice to assess the activity of microbicides against viruses in suspension. 2020; Available at: https://www.astm.org/Standards/E1052.htm. Accessed May 7, 2020.Google Scholar§ 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. Open table in a new tab 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. 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 infection prevention and control of SARS-CoV-2 and the ongoing COVID-19 pandemic.

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