A recent study suggests that a drug originally developed for treating prostate cancer could hold potential in combatting COVID-19 and its various strains.
Men experienced higher instances of severe illness and fatalities during Covid
When the COVID-19 pandemic emerged, it became evident that men were experiencing higher instances of severe illness and fatalities. This observation prompted researchers to explore a possible connection between androgen receptors—molecules that interact with hormones like testosterone—and the infection caused by the SARS-CoV-2 virus.
Prompted by this hypothesis, scientists from the University of Michigan delved into an investigational prostate cancer drug known as proxalutamide. This drug targets an enzyme called TMPRSS2 (transmembrane protease, serine 2), which is regulated by androgen receptors. The researchers aimed to ascertain if proxalutamide could serve as a potential therapeutic agent for COVID-19.
Dr. Arul Chinnaiyan, Director of the Michigan Centre for Translational Pathology and Professor of Pathology, explained, “Given that we were already investigating TMPRSS2’s role as a critical gene driver in over 50 percent of prostate cancer cases, it seemed logical to examine its potential impact on COVID-19. TMPRSS2 plays a pivotal role as a host factor for SARS-CoV-2 to invade lung cells.”
The team conducted an experiment, detailed in the journal PNAS, in which they introduced proxalutamide to cells infected with SARS-CoV-2 to assess its ability to hinder viral entry. The compound operates by binding to androgen receptors, thus curtailing the levels of TMPRSS2 and ACE2, consequently impeding infection.
Impressively, proxalutamide exhibited superior effectiveness compared to other prostate cancer drugs in countering various SARS-CoV-2 variants. This was attributed to its capacity to suppress the androgen receptor.
Moreover, when proxalutamide was combined with the FDA-approved COVID-19 drug remdesivir, it achieved a remarkable 100 per cent inhibition of infection. Dr. Jonathan Sexton, Assistant Professor of Internal Medicine at the University, commented, “This finding highlights the value of repurposing existing drugs for new applications, allowing for swift human evaluations and thereby shortening the timeline from discovery to clinical assessment.”
Emboldened by their positive in vitro outcomes, the researchers proceeded to explore whether the compound could mitigate the cytokine storm, an intense inflammatory response linked to SARS-CoV-2 infection. Employing a mouse model, they demonstrated that the drug reduced lung inflammation and cellular damage, ultimately leading to reduced mortality.
Dr. Chinnaiyan emphasized, “The notion is that proxalutamide might function as a combined therapy alongside remdesivir, attacking the virus from multiple angles, akin to the successful approach used in treating HIV infection.” Currently, proxalutamide is undergoing phase 3 clinical trials for prostate cancer and early clinical assessments for COVID-19 treatment.