Genome-scale CRISPR screen identifies TMEM41B as a multi-function host factor required for coronavirus replication

by Limeng Sun, Changzhi Zhao, Zhen Fu, Yanan Fu, Zhelin Su, Yangyang Li, Yuan Zhou, Yubei Tan, Jingjin Li, Yixin Xiang, Xiongwei Nie, Jinfu Zhang, Fei Liu, Shuhong Zhao, Shengsong Xie, Peng Guiqing

Emerging coronaviruses (CoVs) pose a severe threat to human and animal health worldwide. To identify host factors required for CoV infection, we used α-CoV transmissible gastroenteritis virus (TGEV) as a model for genome-scale CRISPR knockout (KO) screening. Transmembrane protein 41B (TMEM41B) was found to be a bona fide host factor involved in infection by CoV and three additional virus families. We found that TMEM41B is critical for the internalization and early-stage replication of TGEV. Notably, our results also showed that cells lacking TMEM41B are unable to form the double-membrane vesicles necessary for TGEV replication, indicating that TMEM41B contributes to the formation of CoV replication organelles. Lastly, our data from a mouse infection model showed that the KO of this factor can strongly inhibit viral infection and delay the progression of a CoV disease. Our study revealed that targeting TMEM41B is a highly promising approach for the development of broad-spectrum anti-viral therapeutics.