Native and activated antithrombin inhibits TMPRSS2 activity and SARS‐CoV‐2 infection

alexandrossfakianakis shared this article with you from Inoreader Native and activated antithrombin inhibits TMPRSS2 activity and SARS‐CoV‐2 infection via Journal of Medical Virology Abstract Host cell proteases such as TMPRSS2 are critical determinants of SARS-CoV-2 tropism and pathogenesis. Here, we show that antithrombin (AT), an endogenous serine protease inhibitor regulating coagulation, is a broad-spectrum inhibitor of coronavirus infection. Molecular docking and enzyme activity assays demonstrate that AT binds and inhibits TMPRSS2, a serine protease that primes the Spike proteins of coronaviruses for subsequent fusion. Consequently, AT blocks entry driven by the Spikes of SARS-CoV, MERS-CoV, hCoV-229E, SARS-CoV-2 and its variants of concern including Omicron, and suppresses lung cell infection with genuine SARS-CoV-2. Thus, AT is an endogenous inhibitor of SARS-CoV-2 that may be involved in COVID-19 pathogenesis. We further demonstrate that activation of AT by anticoagulants, such as heparin or fondaparinux, increases the anti-TMPRSS2 and anti-SARS-CoV-2 activity of AT, suggesting that repurposing of native and activated AT for COVID-19 tr eatment should be explored. This article is protected by copyright. All rights reserved. View on Web

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