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COVID-19

Breakthrough in COVID-19 Research: New Findings on SARS-CoV-2 Macrodomain and Antiviral Targets

Strategic Insights

— 1 min read

Scientists at the University of California San Francisco (UCSF) have made significant progress in understanding the SARS-CoV-2 macrodomain and its role in the virus's pathogenesis. Their research, published in Science Advances, reveals a new method for fragment linking that can lead to the development of potent antiviral compounds. This breakthrough has significant implications for the treatment and prevention of COVID-19.

Key Takeaways:

  • The SARS-CoV-2 macrodomain is a critical component of the virus's pathogenesis and is an emerging antiviral target.
  • Researchers at UCSF developed a shape-based virtual screening pipeline, FrankenROCS, which combines fragment linking with active learning algorithms to efficiently search vast libraries of compounds.
  • FrankenROCS enabled the identification of potent inhibitors of the SARS-CoV-2 macrodomain with IC50 values better than 10 μM.
  • The lead series of analogs developed through this method has improved membrane permeability, making them more suitable for optimization.
  • This breakthrough has significant implications for the treatment and prevention of COVID-19, offering a promising new avenue for antiviral therapy.

Sources:

  • Exploration of Structure-activity Relationships for the Sars-cov-2 Macrodomain From Shape-based Fragment Linking and Active Learning. Science Advances, 2025;11(22).
  • American Association for the Advancement of Science, 1200 New York Ave, NW, Washington, DC 20005, USA
  • Researchers: James S. Fraser, Galen J. Correy, Moira M. Rachman, Takaya Togo, Stefan Gahbauer, Priyadarshini Jaishankar, Brian K. Shoichet, Adam R. Renslo, Yagmur U. Doruk, Maisie G. V. Stevens, Alan Ashworth, Brian Kelley, Brian Goldman, Molly Schmidt, Trevor Kramer, Patrick Riley, W. Patrick Walters, Dmytro S. Radchenko, and Yurii S. Moroz
  • Supported by: United States Department of Energy (DOE), ALS-ENABLE program - NIH, National Institute of General Medical Sciences, United States Department of Energy (DOE), United States Department of Energy (DOE), NIH National Institute of General Medical Sciences (NIGMS), National Institutes of Health (NIH) - USA, Sanghvi-Agarwal Innovation Award, Relay Therapeutics

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