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Identification of MMP-9 as a Driving Factor in SARS-CoV-2 Entry

Since its emergence in December 2019, SARS-CoV-2 has infected over 200 million people globally. SARS-CoV-2 spike (S) decorates the viral envelope and is responsible for facilitating viral entry into the host cell. To mediate membrane fusion, S must be proteolytically cleaved. For the closely related SARS-CoV S, cleavage at the host cell surface must be facilitated by the serine protease TMPRSS2. We demonstrated that SARS-CoV-2 S can facilitate fusion independent of TMPRSS2 and sought to identify other proteases capable of driving SARS-CoV-2 S-mediated fusion. We show that the ADAMs and MMP inhibitor GI 254023X is capable of substantially reducing SARS-CoV-2 S-mediated syncytium formation. Additionally, we identified MMP-9, a protein target of GI 254023X, as a host protease capable of enhancing SARS-CoV-2 lentivirus entry in HEK293T-ACE2 cells. These results implicate ADAM and MMP proteases, in particular MMP-9, as potential antiviral drug targets against COVID-19 pathogenesis.

Identiferoai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/42771
Date30 September 2021
CreatorsPhan, Alexandra
ContributorsCôté, Marceline
PublisherUniversité d'Ottawa / University of Ottawa
Source SetsUniversité d’Ottawa
LanguageEnglish
Detected LanguageEnglish
TypeThesis
Formatapplication/pdf

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