As part of continued efforts to respond to the COVID-19 pandemic caused by SARS-CoV-2 virus, researchers report the X-ray crystallography structure of the SARS-CoV-2 main protease – one of the best characterized drug targets among coronaviruses. Insights from their study could drive the design of better inhibitors for the novel coronavirus, a step toward urgently needed therapies to fight the global pandemic. For viruses like HIV, effective drugs block the main virus protease – an enzyme that processes proteins critical to virus development. Here, Linlin Zhang and colleagues report the crystal structure of main protease of SARS-CoV-2 at 1.75 angstrom resolution.
Based on studying the structure of the main protease, the researchers optimized inhibitors for existing coronaviruses to develop compound 13b, a potent blocker of the SARS-CoV-2 main protease. They report that 13b has features that improve over existing inhibitors, including an extended half-life in blood plasma. Zhang and colleagues reported a high-resolution structure of 13b bound to the protease. They further tested their leading inhibitor compound in mice, finding that inhalation was well tolerated, and mice did not show any adverse effects. Their results suggest that direct administration of the compound to the lungs may be possible and provide a framework for the development of drugs to combat the novel coronavirus.
Original research article: https://science.sciencemag.org/content/early/2020/03/19/science.abb3405
Feature image: This transmission electron microscope image shows SARS-CoV-2, the virus that causes COVID-19, isolated from a patient in the U.S. Virus particles are shown emerging from the surface of cells cultured in the lab. The spikes on the outer edge of the virus particles give coronaviruses their name, crown-like. Credit: NIAID-RML.