Study finds potential way to prevent infection by wide range of COVID-19 variants

Researchers have found that a new class of compounds currently being tested as possible cancer drugs can inhibit a wide range of SARS-CoV-2 variants in the lab. With further development, the small molecules could potentially provide broad activity against the constantly emerging new strains of the COVID-19 virus. 

Scientists at Dana-Farber Cancer Institute, Yale School of Medicine, and the Broad Institute of MIT and Harvard discovered that a regulator of gene expression, called the mammalian SWI/SNF (also called BAF) chromatin remodeling complex, controls the expression of the ACE2, the cellular receptor or “entry point” used by COVID-19 viruses to infect cells. When mSWI/SNF complexes were disrupted, cells could no longer make ACE2 receptor protein and became resistant to infection by any virus that uses that receptor. The team describes these and other findings in a paper published in Nature Genetics.

Research on mSWI/SNF complexes over the years in the lab of Cigall Kadoch, a Dana-Farber investigator and Broad institute member, has led to experimental drugs currently in phase 1 trials as anti-cancer agents. The research team said these oral drugs are promising for use in COVID-19, since they can inhibit ACE2 activity and, in their study, almost completely blocked viral infection in multiple cell lines and human lung organoids. 

Impact

The formerly potent array of monoclonal antibody treatments for COVID-19 continue to lose their activity as new variants of the virus appear: indeed, one by one, they have gone off the market. The need for more broadly acting agents against new and drug-resistant viruses is great. With the identification of this new target – a druggable chromatin regulatory complex – inhibition of which prevents infection of host cells, the scientists, including co-senior author Craig Wilen of the Yale Cancer Center and members of the Broad’s Genetic Perturbation Platform, have found a promising novel approach to combating the constantly-changing SARS-CoV-2 virus.

Adapted from a research summary from Dana-Farber Cancer Institute.