Functional interrogation of a SARS-CoV-2 host protein interactome identifies unique and shared coronavirus host factors

BioRxiv : the Preprint Server for Biology
H-Heinrich HoffmannCharles M Rice

Abstract

The ongoing SARS-CoV-2 pandemic has devastated the global economy and claimed nearly one million lives, presenting an urgent global health crisis. To identify host factors required for infection by SARS-CoV-2 and seasonal coronaviruses, we designed a focused high-coverage CRISPR-Cas9 library targeting 332 members of a recently published SARS-CoV-2 protein interactome. We leveraged the compact nature of this library to systematically screen four related coronaviruses (HCoV-229E, HCoV-NL63, HCoV-OC43 and SARS-CoV-2) at two physiologically relevant temperatures (33 °C and 37 °C), allowing us to probe this interactome at a much higher resolution relative to genome scale studies. This approach yielded several new insights, including unexpected virus and temperature specific differences in Rab GTPase requirements and GPI anchor biosynthesis, as well as identification of multiple pan-coronavirus factors involved in cholesterol homeostasis. This coronavirus essentiality catalog could inform ongoing drug development efforts aimed at intercepting and treating COVID-19, and help prepare for future coronavirus outbreaks. Focused CRISPR screens targeting host factors in the SARS-CoV-2 interactome were performed for SARS-CoV-2, HCoV-229E, HC...Continue Reading

Citations

Dec 19, 2020·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Hongjie Xia, Pei-Yong Shi
Jan 20, 2021·Journal of Proteome Research·Paige HaasRuth Hüttenhain
Dec 23, 2020·Nature Microbiology·Nora SchmidtMathias Munschauer
May 10, 2021·Frontiers in Cellular and Infection Microbiology·Ronghua DingGuangcai Duan

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