Functional interrogation of a SARS-CoV-2 host protein interactome identifies unique and shared coronavirus host factors.
Cell Host Microbe
; 29(2): 267-280.e5, 2021 02 10.
Article
de En
| MEDLINE
| ID: mdl-33357464
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.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
SARS-CoV-2
/
COVID-19
Type d'étude:
Prognostic_studies
Limites:
Humans
Langue:
En
Journal:
Cell Host Microbe
Sujet du journal:
MICROBIOLOGIA
Année:
2021
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique