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dc.contributor.authorSiniavin, Andrei E
dc.contributor.authorStreltsova, Maria A
dc.contributor.authorNikiforova, Maria A
dc.contributor.authorKudryavtsev, Denis S
dc.contributor.authorGrinkina, Svetlana D
dc.contributor.authorGushchin, Vladimir A
dc.contributor.authorMozhaeva, Vera A
dc.contributor.authorStarkov, Vladislav G
dc.contributor.authorOsipov, Alexey V
dc.contributor.authorLummis, Sarah CR
dc.contributor.authorTsetlin, Victor I
dc.contributor.authorUtkin, Yuri N
dc.date.accessioned2022-01-06T12:57:05Z
dc.date.available2022-01-06T12:57:05Z
dc.date.issued2021-12
dc.identifier.issn1420-682X
dc.identifier.otherPMC8554752
dc.identifier.other34714362
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/332231
dc.description.abstractThe COVID-19 pandemic caused by SARS-CoV-2 requires new treatments both to alleviate the symptoms and to prevent the spread of this disease. Previous studies demonstrated good antiviral and virucidal activity of phospholipase A2s (PLA2s) from snake venoms against viruses from different families but there was no data for coronaviruses. Here we show that PLA2s from snake venoms protect Vero E6 cells against SARS-CoV-2 cytopathic effects. PLA2s showed low cytotoxicity to Vero E6 cells with some activity at micromolar concentrations, but strong antiviral activity at nanomolar concentrations. Dimeric PLA2 from the viper Vipera nikolskii and its subunits manifested especially potent virucidal effects, which were related to their phospholipolytic activity, and inhibited cell-cell fusion mediated by the SARS-CoV-2 spike glycoprotein. Moreover, PLA2s interfered with binding both of an antibody against ACE2 and of the receptor-binding domain of the glycoprotein S to 293T/ACE2 cells. This is the first demonstration of a detrimental effect of PLA2s on β-coronaviruses. Thus, snake PLA2s are promising for the development of antiviral drugs that target the viral envelope, and could also prove to be useful tools to study the interaction of viruses with host cells.
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.sourceessn: 1420-9071
dc.sourcenlmid: 9705402
dc.subjectSurface plasmon resonance
dc.subjectMolecular modelling
dc.subjectReplication Cycle
dc.subjectReceptor Binding Domain
dc.subjectPseudotyped Sars-cov-2 Virus
dc.subjectTime-Of-Drug-Addition Assay
dc.titleSnake venom phospholipase A2s exhibit strong virucidal activity against SARS-CoV-2 and inhibit the viral spike glycoprotein interaction with ACE2.
dc.typeArticle
dc.date.updated2022-01-06T12:57:05Z
prism.endingPage7794
prism.issueIdentifier23
prism.publicationNameCell Mol Life Sci
prism.startingPage7777
prism.volume78
dc.identifier.doi10.17863/CAM.79677
dcterms.dateAccepted2021-10-14
rioxxterms.versionofrecord10.1007/s00018-021-03985-6
rioxxterms.versionVoR
dc.contributor.orcidSiniavin, Andrei E [0000-0001-7576-2059]
dc.contributor.orcidStreltsova, Maria A [0000-0002-5403-0753]
dc.contributor.orcidNikiforova, Maria A [0000-0001-5823-6508]
dc.contributor.orcidKudryavtsev, Denis S [0000-0002-0313-9193]
dc.contributor.orcidGushchin, Vladimir A [0000-0002-9397-3762]
dc.contributor.orcidTsetlin, Victor I [0000-0002-7980-6191]
dc.contributor.orcidUtkin, Yuri N [0000-0002-4609-970X]
dc.identifier.eissn1420-9071
pubs.funder-project-idРоссийский Фонд Фундаментальных Исследований (20-04-60277)
cam.issuedOnline2021-10-29


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