Viral and cellular translation during SARS‐CoV‐2 infection

SARS‐CoV‐2 is a betacoronavirus that emerged in China in December 2019 and which is the causative agent of the Covid‐19 pandemic. This enveloped virus contains a large positive‐sense single‐stranded RNA genome. In this review, we summarize the current knowledge on the molecular mechanisms for the translation of both viral transcripts and cellular messenger RNAs. Non‐structural proteins are encoded by the genomic RNA and are produced in the early steps of infection. In contrast, the structural proteins are produced from subgenomic RNAs that are translated in the late phase of the infectious program. Non‐structural protein 1 (NSP1) is a key molecule that regulates both viral and cellular translation. In addition, NSP1 interferes with multiple steps of the interferon I pathway and thereby blocks host antiviral responses. Therefore, NSP1 is a drug target of choice for the development of antiviral therapies. This Review gives an overview of translation during SARS‐CoV‐2 infection. This encompasses molecular mechanisms for viral translation of both genomic and subgenomic transcripts. Host translation is shut down by NSP1‐mediated mechanisms. mRNAs involved in type I interferon antiviral response are specifically silenced. Different functions of NSP1 as an essential virulent factor are discussed for the main coronavirus families.