J.T. Poirier - March 17, 2021

J.T. Poirier, PhD, Assistant Professor of Medicine, Director, Preclinical Therapeutics Program, Perlmutter Cancer Center, NYU Grossman School of Medicine, Genome-scale Identification of SARS-CoV-2 and Pan-coronavirus Host Factor Networks

Dr. Poirier’s group works to systematically identify the host proteins that SARS-CoV-2 requires to infect cells, with the ultimate goal of uncovering druggable targets that may be leveraged to treat or prevent SARS-CoV-2 infection. The group uses a CRISPR-Cas9 system to iteratively disrupt potential host factors, after which a coronavirus is introduced. The resulting viability of the cell culture is then a measure of the necessity of these host factors for coronavirus infection. Genome-wide screening revealed several critical host factors common to several coronaviruses including SARS-CoV-2. TMEM41B, related to lipid mobilization in early autophagy, was one strongly implicated target in all coronaviruses screened. SARS-CoV-2 was also strikingly sensitive to disruption of various steps of SREBP signaling—a lipid biosynthesis pathway—as well as the heparin sulfate biosynthetic pathway. Both of these pathways are notable because they are inhibitable by well-characterized small molecule drugs. Ongoing work in Dr. Poirier’s group seeks to utilize higher-resolution screens of the coronavirus:host protein interactome and libraries of specifically druggable proteins to narrow the search for pharmacologically tractable targets.