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Optimization and Deoptimization of Codons in SARS-CoV-2 and Related Implications for Vaccine Development

Adv Sci (Weinh) . . 2023-08; 
Xinkai Wu, Ke-Jia Shan, Fuwen Zan, Xiaolu Tang, Zhaohui Qian, Jian Lu
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Gene Synthesis Western Blot Analysis of S Protein Expression: The coding sequences of the S protein for BA.2.12.1, BA.4/5, or XBB.1.5 variants with various CAIs were synthesized by GeneScript (Nanjing, China) and cloned into the pcDNA 3.1 plasmid between the Hind III and Xba I sites. Get A Quote


The spread of coronavirus disease 2019 (COVID-19), caused by severe respiratory syndrome coronavirus 2 (SARS-CoV-2), has progressed into a global pandemic. To date, thousands of genetic variants have been identified among SARS-CoV-2 isolates collected from patients. Sequence analysis reveals that the codon adaptation index (CAI) values of viral sequences have decreased over time but with occasional fluctuations. Through evolution modeling, it is found that this phenomenon may result from the virus's mutation preference during transmission. Using dual-luciferase assays, it is further discovered that the deoptimization of codons in the viral sequence may weaken protein expression during virus evolution, indicatin... More


SARS-CoV-2; codon optimization; codon usage bias; spike protein; synonymous mutations; vaccine design.