Abstract
The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has devastated the global economy and claimed more than 1.7 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 SARS-CoV-2 at two physiologically relevant temperatures along with three related coronaviruses (human coronavirus 229E [HCoV-229E], HCoV-NL63, and HCoV-OC43), allowing us to probe this interactome at a much higher resolution than genome-scale studies. This approach yielded several insights, including potential virus-specific differences in Rab GTPase requirements and glycosylphosphatidylinositol (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 coronavirus disease 2019 (COVID-19) and help prepare for future coronavirus outbreaks.
Keywords: COVID-19; CRISPR; HCoV; HCoV-229E; HCoV-NL63; HCoV-OC43; SARS-CoV-2; coronavirus; virus-host interactome.
【저자키워드】 COVID-19, SARS-CoV-2, coronavirus, HCoV-OC43, CRISPR, HCoV, HCoV-229E, HCoV-NL63, virus-host interactome, 【초록키워드】 coronavirus disease, coronavirus, pandemic, Infection, Outbreaks, Health, temperature, seasonal coronaviruses, CRISPR-Cas9, acute respiratory syndrome, Factor, help, effort, SARS-CoV-2 protein, GTPase, cholesterol homeostasis, human coronavirus 229E, probe, Host, approach, Rab, identify, involved, required, much higher, presenting, claimed, GPI, 【제목키워드】 coronavirus, Factor, host protein, Host, identify, unique,