Study shows prostate cancer drug may help fight Covid-19, variants

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.  

Researchers have found that a drug to fight prostate cancer may also help against Covid and its variants.

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 researchers from the University of Michigan to look into a drug in development to treat prostate cancer called proxalutamide, which works by blocking an enzyme called TMPRSS2 (transmembrane protease, serine 2) that is regulated by androgen receptors, as a potential therapeutic for Covid.

"We were already studying TMPRSS2 as part of the key gene driver of over 50 per cent of prostate cancer, so it made sense to look at it as TMPRSS2 is an important host factor for SARS-CoV2 to enter cells in the lung," said Arul Chinnaiyan, director of the Michigan Centre for Translational Pathology and Professor of Pathology.

In the study, published in the journal PNAS, 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 also worked better than other prostate cancer drugs against multiple variants of SARS-CoV2 due to its ability to break down the androgen receptor.

In addition, proxalutamide, when combined with the US FDA-approved Covid drug remdesivir, blocked infection by 100 per cent.

"This discovery underscores the utility of testing existing drugs for new applications that can be rapidly evaluated in humans to shorten the timeline from discovery to clinical evaluation," said Jonathan Sexton, Assistant Professor of Internal Medicine at the University.

Buoyed 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.

"The thought is that proxalutamide could work as a combined therapy with remdesivir, hitting the virus from multiple angles, much as combination therapy works so well for HIV infection," Chinnaiyan said.

The drug is currently in phase 3 clinical trials for prostate cancer and early clinical trials for Covid.
 

 

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