Craig Wilen - August 26, 2020

Craig Wilen, MD, PhD, Assistant Professor of Laboratory Medicine and of Immunobiology; Medical Director, Immune Monitoring Core Facility, Yale School of Medicine, "Genome-wide CRISPR screen identifies host genes essential for SARS-CoV-2 infection"

Dr. Wilen discussed the significance of host-virus interactions on prognostics and therapeutics because it can inform why clinical presentation is so variable as well as develop therapeutics against host targets. SARS-CoV-2 uses ACE2 receptors to enter the cell, and then CTSL or TMPRSS2 for proteolytic activity. Using a CRISPR forward screen on Vero E6 cells, they strikingly found that chromatin and histone remodelers such as SWI/SNF gene SMARCA4 were important to viral entry. Pathway analysis found the SWI/SNF complex to be pro-viral. Others include Smad3 and Smad4. HMGB1 is a pleiotropic protein that is pro-viral for SARS-CoV2, is regulated by ACE2 and CTSL, and it is critical for viral entry. Some small molecules targeting Smad3 and the SWI/SNF complex were found to inhibit viral replication.