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dc.contributor.authorSalgueiro, Bruno A.
dc.contributor.authorSaramago, Margarida
dc.contributor.authorTully, Mark D.
dc.contributor.authorIssoglio, Federico
dc.contributor.authorSilva, Sara T. N.
dc.contributor.authorPaiva, Ana C. F.
dc.contributor.authorArraiano, Cecília M.
dc.contributor.authorMatias, Pedro M.
dc.contributor.authorMatos, Rute G.
dc.contributor.authorMoe, Elin
dc.contributor.authorRomão, Célia V.
dc.date.accessioned2024-10-14T10:31:40Z
dc.date.available2024-10-14T10:31:40Z
dc.date.issued2024-03-28
dc.description.abstractOver recent years, we have been living under a pandemic, caused by the rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). One of the major virulence factors of Coronaviruses is the Non-structural protein 1 (Nsp1), known to suppress the host cells protein translation machinery, allowing the virus to produce its own proteins, propagate and invade new cells. To unveil the molecular mechanisms of SARS-CoV2 Nsp1, we have addressed its biochemical and biophysical properties in the presence of calcium, magnesium and manganese. Our findings indicate that the protein in solution is a monomer and binds to both manganese and calcium, with high affinity. Surprisingly, our results show that SARS-CoV2 Nsp1 alone displays metal-dependent endonucleolytic activity towards both RNA and DNA, regardless of the presence of host ribosome. These results show Nsp1 as new nuclease within the coronavirus family. Furthermore, the Nsp1 double variant R124A/K125A presents no nuclease activity for RNA, although it retains activity for DNA, suggesting distinct binding sites for DNA and RNA. Thus, we present for the frst time, evidence that the activities of Nsp1 are modulated by the presence of different metals, which are proposed to play an important role during viral infection. This research contributes significantly to our understanding of the mechanisms of action of Coronaviruses.en_US
dc.identifier.citationSalgueiro, Saramago, Tully, Issoglio, Silva, Paiva, Arraiano, Matias, Matos, Moe, Romão. SARS-CoV2 Nsp1 is a metal-dependent DNA and RNA endonuclease. Biometals. 2024en_US
dc.identifier.cristinIDFRIDAID 2259846
dc.identifier.doi10.1007/s10534-024-00596-z
dc.identifier.issn0966-0844
dc.identifier.issn1572-8773
dc.identifier.urihttps://hdl.handle.net/10037/35212
dc.language.isoengen_US
dc.publisherSpringer Natureen_US
dc.relation.journalBiometals
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2024 The Author(s)en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en_US
dc.rightsAttribution 4.0 International (CC BY 4.0)en_US
dc.titleSARS-CoV2 Nsp1 is a metal-dependent DNA and RNA endonucleaseen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's license is described as Attribution 4.0 International (CC BY 4.0)