Prostate cancer drug potential against COVID

At the outset of the COVID pandemic, men appeared to suffer higher rates of severe illness and death, leading researchers to suspect a link between androgen receptors—which bind to hormones like testosterone--and SARS-CoV-2 viral infection.

This observation spurred Michigan Medicine researchers to look into a drug in development to treat prostate cancer called proxalutamide, which works by blocking an enzyme called transmembrane protease, serine 2 that is regulated by androgen receptors, as a potential therapeutic for COVID.

The team added proxalutamide to cells infected with SARS-Co-V2 to monitor its ability to block viral entry. The compound works by binding to androgen receptors, inhibiting levels of TMPRSS2 and ACE2, and blocking infection.

Proxalutamide worked better than other prostate cancer drugs against multiple variants of SARS-CoV2 due to its ability to break down the androgen receptor.

Additionally, proxalutamide, when combined with FDA-approved COVID drug remdesivir, blocked infection by 100%. By their in vitro results, the team looked to see whether the compound could stop the so-called cytokine storm, or severe inflammatory response, caused by SARS-CoV-2 infection.

Using a mouse model, they demonstrated that the drug reduced inflammation and cell death in the lungs of mice and reduced mortality.

Reference: “Proxalutamide reduces SARS-CoV-2 infection and associated inflammatory response,” PNAS. DOI: 10.1073/pnas.2221809120