首页|Decavanadate interactions with the elements of the SARS-CoV-2 spike protein highlight the potential role of electrostatics in disrupting the infectivity cycle
Decavanadate interactions with the elements of the SARS-CoV-2 spike protein highlight the potential role of electrostatics in disrupting the infectivity cycle
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NSTL
Elsevier
? 2022 Elsevier Inc.Polyoxidometalates (POMs) exhibit a range of biological properties that can be exploited for a variety of therapeutic applications. However, their potential utility as antivirals has been largely overlooked in the ongoing efforts to identify safe, effective and robust therapeutic agents to combat COVID-19. We focus on decavanadate (V10), a paradigmatic member of the POM family, to highlight the utility of electrostatic forces as a means of disrupting molecular processes underlying the SARS-CoV-2 entry into the host cell. While the departure from the traditional lock-and-key approach to the rational drug design relies on less-specific and longer-range interactions, it may enhance the robustness of therapeutic agents by making them less sensitive to the viral mutations. Native mass spectrometry (MS) not only demonstrates the ability of V10 to associate with the receptor-binding domain of the SARS-CoV-2 spike protein, but also provides evidence that this association disrupts the protein binding to its host cell-surface receptor. Furthermore, V10 is also shown to be capable of binding to the polybasic furin cleavage site within the spike protein, which is likely to decrease the effectiveness of the proteolytic processing of the latter (a pre-requisite for the viral fusion with the host cell membrane). Although in vitro studies carried out with SARS-CoV-2 infected cells identify V10 cytotoxicity as a major factor limiting its utility as an antiviral agent, the collected data provide a compelling stimulus for continuing the search for effective, robust and safe therapeutics targeting the novel coronavirus among members of the POM family.
Favre D.、Kaltashov I.A.、Harmon J.F.、Zhang A.、Miller M.S.
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Department of Chemistry University of Massachusetts-Amherst
Institute for Applied Life Sciences University of Massachusetts-Amherst
Michael G. DeGroote Institute for Infectious Disease Research McMaster Immunology Research Centre Department of Biochemistry and Biomedical Sciences McMaster University
NSTL
Elsevier
