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Virucidal action mechanism of alcohol and divalent cations against human adenovirus

Martín-González, Natalia, Vieira Gonçalves, Leonam, Condezo, Gabriela N., San Martín, Carmen, Rubiano Saavedra, María, Fallis, Ian, Rubino, Joseph R., Ijaz, M. Khalid, Maillard, Jean-Yves and De Pablo, Pedro J. 2020. Virucidal action mechanism of alcohol and divalent cations against human adenovirus. Frontiers in Molecular Biosciences 7 , 570914. 10.3389/fmolb.2020.570914

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Abstract

Hygiene and disinfection practices play an important role at preventing spread of viral infections in household, industrial and clinical settings. Although formulations based on >70% ethanol are virucidal, there is a currently a need to reformulate products with much lower alcohol concentrations. It has been reported that zinc can increase the virucidal activity of alcohols, although the reasons for such potentiation is unclear. One approach in developing virucidal formulations is to understand the mechanisms of action of active ingredients and formulation excipients. Here, we investigated the virucidal activity of alcohol (40% w/v) and zinc sulfate (0.1% w/v) combinations and their impact on a human adenovirus (HAdV) using, nucleic acid integrity assays, atomic force microscopy (AFM) and transmission electron microscopy (TEM). We observed no difference in virucidal activity (5 log10 reduction in 60 min) against between an ethanol only based formulation and a formulation combining ethanol and zinc salt. Furthermore, TEM imaging showed that the ethanol only formulation produced gross capsid damage, whilst zinc-based formulation or formulation combining both ethanol and zinc did not affect HAdV DNA. Unexpectedly, the addition of nickel salt (5 mM NiCl2) to the ethanol-zinc formulation contributed to a weakening of the capsid and alteration of the capsid mechanics exemplified by AFM imaging, together with structural capsid damage. The addition of zinc sulfate to the ethanol formulation did not add the formulation efficacy, but the unexpected mechanistic synergy between NiCl2 and the ethanol formulation opens an interesting perspective for the possible potentiation of an alcohol-based formulation. Furthermore, we show that AFM can be an important tool for understanding the mechanistic impact of virucidal formulation.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Chemistry
Additional Information: This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).
Publisher: Frontiers Media
ISSN: 2296-889X
Funders: Spanish State Research Agency and the European Regional Development Fund. Reckitt Benckiser funded a PhD Studentship
Date of First Compliant Deposit: 11 January 2021
Date of Acceptance: 25 November 2020
Last Modified: 12 Jan 2021 10:00
URI: http://orca.cf.ac.uk/id/eprint/137539

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