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

RNA Biol. 2024 Jan;21(1):1-18. doi: 10.1080/15476286.2024.2433830. Epub 2024 Dec 4.

Abstract

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 broad-spectrum therapeutics. Protein translation is vital for SARS-CoV-2 replication, producing early non-structural 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.

Keywords: RNA cleavage; SARS-CoV-2; conserved RNA element; stem-loop; translation; translation inhibition; untranslated region.

Publication types

  • Review

MeSH terms

  • Antiviral Agents* / pharmacology
  • Antiviral Agents* / therapeutic use
  • COVID-19 / virology
  • COVID-19 Drug Treatment* / methods
  • Drug Development
  • Genome, Viral*
  • Humans
  • Protein Biosynthesis / drug effects
  • Protein Biosynthesis / genetics
  • RNA, Viral* / genetics
  • RNA, Viral* / metabolism
  • SARS-CoV-2* / drug effects
  • SARS-CoV-2* / genetics
  • Virus Replication / drug effects
  • Virus Replication / genetics

Substances

  • Antiviral Agents
  • RNA, Viral

Grants and funding

This work was supported by the Natural Science Foundation of Sichuan Province [2022NSFSC0722]