The main protease (M^pro) from SARS-CoV-2 triggers plasma clotting in vitro by activating coagulation factors VII and FXII.

ABSTRACT: Although the connection between COVID-19 and coagulopathy has been clear since the beginning of SARS-CoV-2 pandemic, the underlying molecular mechanisms remain elusive. Available data support that the hyper-coagulant state is sustained by systemic inflammation. Here we show that the SARS-CoV-2 main protease (M^pro) can play a direct role in the activation of coagulation. Adding M^pro to human plasma increased clotting probability by 3-fold. Enzymatic assays and degradomics analysis indicate that M^pro cleaves and activates coagulation factors VII and XII. This activity is compatible with an extended secondary specificity of M^pro for R↓X that diverge from its well-established preference for LQ↓X. This finding is supported by HDX-MS characterization o

SUBMITTER: Pagotto A 

PROVIDER: S-EPMC12316959 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature