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Updated: May 5, 2026

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Lock out: targeting TMPRSS2 to block influenza and coronaviruses

Lu Zhang1,2, Markus Hoffmann1, Stefan Pöhlmann1,2

  • 1Infection Biology Unit, German Primate Center - Leibniz Institute for Primate Research, Göttingen, Germany.

Journal of Virology
|May 4, 2026
PubMed

Insights

Transmembrane protease serine 2 (TMPRSS2) is crucial for activating coronaviruses and influenza A viruses (IAV). Targeting TMPRSS2 offers a promising strategy for developing new antiviral therapies against these respiratory pathogens.

Area of Science:

  • Virology
  • Biochemistry
  • Pharmacology

Background:

  • Coronaviruses and influenza A viruses (IAV) cause severe respiratory illness with pandemic potential.
  • Viral glycoprotein priming by host proteases is essential for infectivity, representing a key target for antiviral strategies.

Purpose of the Study:

  • To review the critical role of transmembrane protease serine 2 (TMPRSS2) in coronavirus and IAV priming.
  • To summarize recent advancements in understanding TMPRSS2 biology and its inhibition for therapeutic purposes.

Main Methods:

  • Literature review of studies on TMPRSS2 function in viral infections.
  • Analysis of research on the substrate specificity and pharmacological inhibition of TMPRSS2.

Main Results:

  • TMPRSS2 plays a central role in priming both coronavirus and IAV glycoproteins.
  • Extensive research, intensified by the COVID-19 pandemic, has elucidated TMPRSS2's function and potential as a therapeutic target.

Conclusions:

  • TMPRSS2 is a significant host dependency factor for coronaviruses and IAV.
  • Targeting TMPRSS2 presents a viable therapeutic avenue for combating infections caused by these viruses.
Keywords:
SARS-CoV-2TMPRSS2primingproteasespike

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