In the article, “Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection”, Yale Pathology research members Qin Yan, Katerina Politi, Wesley Cai, Shang-Min Zhang, Fernando de Minguel, and Huacui Chen participated in characterization of the epigenetic regulators identified from a genome-wide CRISPR screens in Vero-E6 cells with SARS-CoV-2, MERS-CoV, bat coronavirus HKU5 expressing SARS-CoV-1 spike protein, or VSV expressing SARS-CoV-2 spike protein.
The research team has identified pro-viral host factors including epigenetic regulators (HMGB1, SWI/SNF, KDM6A, and JMJD6), and receptor ACE2 and protease Cathepsin L. They have demonstrated that HMGB1 regulates ACE2 expression, which is critical for the entry of coronaviruses SARS-CoV-2, SARS-CoV-1, and NL63. The team has also shown that “small molecule antagonists of identified gene” can inhibit the SARS-CoV-2 infection of both human and monkey cells.
In conclusion, the research teams’ above findings are critical for further understanding of the pathogenesis of SARS-CoV-2 and treatment of COVID-19.