Pan-SARS-CoV-2 prophylactic and therapeutic - TMPRSS2 inhibitor

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SUMMARY

The discussion focuses on the role of TMPRSS2 inhibitors in the context of SARS-CoV-2, highlighting their potential to interfere with the reconfiguration of the Spike protein into its active form. Published on March 28, 2022, in Nature, the research indicates that while TMPRSS2 inhibitors may be effective for short-term prophylaxis or treatment, their long-term use is questionable due to potential side effects linked to the inhibition of a human protein essential for normal bodily functions. The study primarily tests the drug in cell culture, emphasizing the need for further research in intact organisms to assess systemic effects.

PREREQUISITES
  • Understanding of TMPRSS2 protein functions in human physiology
  • Knowledge of SARS-CoV-2 Spike protein structure and function
  • Familiarity with antiviral drug mechanisms targeting host proteins
  • Basic concepts of pharmacology related to drug efficacy and toxicity
NEXT STEPS
  • Research the implications of TMPRSS2 inhibition on human health
  • Explore antiviral drug development targeting host proteins
  • Investigate the effects of systemic administration of TMPRSS2 inhibitors
  • Study the methodologies for testing drug efficacy in intact organisms
USEFUL FOR

This discussion is beneficial for virologists, pharmacologists, and healthcare professionals involved in antiviral research and treatment strategies for COVID-19.

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Note that TMPRSS2 is a human protein that has normal functions in the human body aside from being hijacked to help process the SARS-CoV-2 spike protein. While there are successful antiviral drugs that target host proteins, these drugs are more likely to have side effects that could limit the use or efficacy of the drug. For example, this drug would not seem like a good candidate for long term prophylactic use, though it could potentially be used for short term prophylaxis in exposed individuals or for treatment if toxicity is not an issue. Notably, the paper (at least from reading the abstract) tests the drug only in cell culture while it would be important to test the drug in intact organisms to see if systemic administration of the drug has any negative effects from loss/reduction of TMPRSS2 function across the body.
 
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