Novel Glucocorticoid and Androgen Receptor Modulator Shows Promise in Treating COVID-19

Strategic Insights -

New research from Colorado State University has identified a potential therapeutic target for COVID-19, using a novel glucocorticoid and androgen receptor modulator that reduces viral entry and inflammatory responses in the Syrian hamster model of SARS-CoV-2 infection. The study, published in Frontiers in Immunology, highlights the potential of PT150 to mitigate the effects of SARS-CoV-2 and provides a promising lead for further clinical development.

Key Takeaways:

  • The study found that oral administration of PT150 caused a dose-dependent decrease in replication of SARS-CoV-2 in lung tissue and expression of ACE2 and TMPRSS2.
  • PT150 also resulted in a significant reduction in lung hypercellularity, infiltration of macrophages and CD4+ T-cells, and tissue damage.
  • Molecular docking studies suggest that PT150 binds to the co-activator interface of the ligand-binding domain of both AR and GR, acting as an allosteric modulator and transcriptional repressor of these receptors.
  • Phylogenetic analysis revealed a high degree of sequence identity maintained across multiple species, including humans, suggesting that the mechanism of action observed in Syrian hamsters would likely be predictive of positive outcomes in patients.
  • The study concludes that PT150 is a strong candidate for further clinical development for the treatment of COVID-19 across variants of SARS-CoV-2.

Statistics:

  • 2.5 x 10^4 TCID50/ml equivalents of SARS-CoV-2 (strain 2019-nCoV/USA-WA1/2020) were used to infect animals in the study.
  • PT150 was administered at 30 and 100 mg/Kg/day for a total of 7 days.
  • The study involved the examination of animals at 3, 5, and 7 days post-infection (DPI) for lung histopathology, viral load, and production of proteins regulating the progression of SARS-CoV-2 infection.
  • Phylogenetic analysis revealed a high degree of sequence identity maintained across multiple species, including humans.

Sources:

  • A Novel Glucocorticoid and Androgen Receptor Modulator Reduces Viral Entry and Innate Immune Inflammatory Responses in the Syrian Hamster Model of SARS-CoV-2 Infection. Frontiers in Immunology, 2022, 13.
  • Frontiers in Immunology - http://journal.frontiersin.org/journal/immunology
  • The publisher for Frontiers in Immunology is Frontiers Media S.A.