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
Affiliations
Shan-Na Wu
Department of Pharmaceutics, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, China
Ting Xiao
Key Laboratory of Birth Defects and Related Diseases of Women and Children, Children’s Medicine Key Laboratory of Sichuan Province, Department of Pharmacy/Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, China
Hui Chen
Key Laboratory of Birth Defects and Related Diseases of Women and Children, Children’s Medicine Key Laboratory of Sichuan Province, Department of Pharmacy/Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, China
Xiao-Hong Li
Department of Pharmaceutics, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, China
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.
