University Of Michigan Study Finds That Proxalutamide Inhibits Various SARS-CoV-2 Variants And Reduces COVID-19 Associated Inflammatory Response
Thailand Medical News Team Aug 06, 2023 8 months, 3 weeks, 8 hours, 9 minutes ago
COVID-19 Drugs: The COVID-19 pandemic has wreaked havoc worldwide, prompting scientists and researchers to explore innovative therapeutics to combat the SARS-CoV-2 virus. While vaccines have been claimed to prevent severe disease, the emergence of new variants and breakthrough infections highlight the need for effective antiviral drugs. In this context, the University of Michigan conducted a groundbreaking study to investigate the potential of proxalutamide, an androgen receptor (AR) antagonist, as a treatment option for COVID-19.
The Role of Androgen Receptor in COVID-19
Early in the pandemic, it was observed that males faced a higher risk of severe COVID-19 outcomes, leading researchers to explore the connection between androgen receptors and the disease. TMPRSS2, a gene regulated by androgen receptors, plays a critical role in SARS-CoV-2 entry into host cells. This association sparked interest in investigating AR-targeting drugs as potential therapeutics for COVID-19.
Proxalutamide-A Potential COVID-19 Antiviral Candidate
Proxalutamide, originally developed as an AR antagonist for advanced prostate cancer, showed promising results in initial clinical studies for COVID-19 treatment. However, due to a retraction of one of the publications, further validation was necessary. The drug is currently in phase 3 clinical trials for COVID-19, both in outpatient and hospital settings in various countries, including the United States.
In Vitro Findings
The
COVID-19 Drugs study demonstrated that proxalutamide, similar to enzalutamide (another AR antagonist), effectively decreased AR signaling and the expression of TMPRSS2 and ACE2, the SARS-CoV-2 receptor.
However, proxalutamide exhibited an advantage over enzalutamide, as it led to the degradation of AR protein.
Importantly, proxalutamide demonstrated potent antiviral activity, inhibiting SARS-CoV-2 infection with an IC50 value of 97 nM, compared to 281 nM for enzalutamide. Moreover, the drug was effective against multiple SARS-CoV-2 variants and synergized with the antiviral drug remdesivir.
In Vivo Studies
In animal models, proxalutamide showed promise in reducing the cytokine storm, a hyperactivation of the immune system that can lead to severe outcomes in COVID-19 patients. It improved overall survival in mouse models of the TNFα and IFNγ-induced cytokine storm triggered by SARS-CoV-2 infection. The drug was associated with increased levels of NRF2, a transcription factor responsible for mediating cellular antioxidant responses, and decreased lung inflammation.
Clinical Trials and Ongoing Studies
Multiple phase 3 clinical trials of proxalutamide for COVID-19 treatment are currently underway in different countries. Early results from one trial in outpatients showed a reduction in hospitalization and deaths compared to the placebo. The ongoing trials in both outpatient and hospitalized settings will provide further evidence of the drug's efficacy in treating COVID-19.
Discussion and Future Prospects
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The findings of the University of Michigan study indicate that proxalutamide has potential as an antiviral agent against SARS-CoV-2 and may offer positive clinical benefits. While other AR-targeting drugs showed mixed results, proxalutamide's distinct mechanism of action and higher potency in inhibiting viral infection warrant further exploration. As more clinical data emerges from the ongoing phase 3 trials, the medical community eagerly anticipates the development of an effective therapeutic option to combat COVID-19.
Conclusion
The COVID-19 pandemic has been a global challenge, necessitating the development of innovative antiviral therapeutics. Proxalutamide, an androgen receptor antagonist, has shown promise in inhibiting SARS-CoV-2 infection and reducing COVID-19-associated inflammatory responses. The results of the University of Michigan study indicate that proxalutamide deserves further investigation as a potential treatment for COVID-19.
The study findings were published in the peer reviewed journal: PNAS.
https://www.pnas.org/doi/10.1073/pnas.2221809120
MEDICAL DISCLAIMER: Please note that this article is based simply as research findings and not as medical advice. Proxalutamide has not been approved by any regulatory agency around the world for COVID-19. Please do not attempt to take Proxalutamide without consulting a licensed medical doctor first.To a certain extent, Proxalutamidecan be regarded as a chemical castration drug!
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