Decoding the genome of SARS-CoV-2: a pathway to drug development through translation inhibition

Shan-Na Wu; Ting Xiao; Hui Chen; Xiao-Hong Li

Shan-Na Wu, Ting Xiao, Hui Chen, Xiao-Hong Li

RNA Biology, doi:10.1080/15476286.2024.2433830

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the coronavirus disease 2019 (COVID-19) pandemic and is continuously spreading globally. The continuous emergence of new SARS-CoV-2 variants keeps posing threats, highlighting the need for fast-acting, mutation-resistant broadspectrum therapeutics. Protein translation is vital for SARS-CoV-2 replication, producing early nonstructural proteins for RNA replication and transcription, and late structural proteins for virion assembly. Targeted blocking of viral protein translation is thus a potential approach to developing effective anti-SARS-CoV-2 drugs. SARS-CoV-2, as an obligate parasite, utilizes the host's translation machinery. Translation-blocking strategies that target the SARS-CoV-2 mRNA, especially those that target its conserved elements are generally preferred. In this review, we discuss the current understanding of SARS-CoV-2 translation, highlighting the important conserved motifs and structures involved in its regulation. We also discuss the current strategies for blocking SARS-CoV-2 translation through viral RNA degradation or RNA element dysfunction.

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