Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

VIRAL INFECTION

Clotting and SARS-CoV-2 entry

Besides the cellular attachment receptor ACE2, SARS-CoV-2 also requires host proteases, such as TMPRSS2, for entry. These proteases cleave spike, thereby activating it. In a screen to identify entry inhibitors, Kastenhuber et al. noticed that some anticoagulants reduced spike-pseudotyped virus entry, leading the authors to speculate that coagulation factors might also process spike. Indeed, thrombin and factor Xa cleaved SARS-CoV-2 spike similarly to TMPRSS2 and increased infection of cell lines with spike-pseudotyped virus as well as of lung organoids with authentic SARS-CoV-2. Finally, the authors tested a range of protease inhibitors and anticoagulants and found variable reduction of spike cleavage, with nafamostat, a serine protease inhibitor in clinical use as an anticoagulant, having the broadest inhibitory effect. The authors speculate that activation of coagulation during infection might further increase SARS-CoV-2 entry and that early treatment with anticoagulants might prevent this feedback loop.

References

Original article

  • Kastenhuber, E. R. et al. Coagulation factors directly cleave SARS-CoV-2 spike and enhance viral entry. eLife 11, e77444 (2022)

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ursula Hofer.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Hofer, U. Clotting and SARS-CoV-2 entry. Nat Rev Microbiol 20, 317 (2022). https://doi.org/10.1038/s41579-022-00729-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41579-022-00729-6

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing