Lost in translation: codon optimization inactivates SARS-CoV-2 RdRp
Lost in translation: codon optimization inactivates SARS-CoV-2 RdRp
ABSTRACT RNA-dependent RNA polymerase (RdRp) is a primary target for antivirals. We report that Nsp12, a catalytic subunit of SARS-CoV-2 RdRp, produces an inactive enzyme when codon-optimized for bacterial expression. We also show that accessory subunits, NTPs, and translation by slow ribosomes partially rescue Nsp12. Our findings have implications for functional studies and identification of novel inhibitors of RdRp and for rational design of other biotechnologically and medically important expression systems.
Svetlov Vladimir、Wang Bing、Nudler Evgeny、Artsimovitch Irina
Department of Biochemistry and Molecular Pharmacology, New York University School of MedicineDepartment of Microbiology, The Ohio State University||The Center for RNA Biology, The Ohio State UniversityDepartment of Biochemistry and Molecular Pharmacology, New York University School of Medicine||Howard Hughes Medical Institute, New York University School of MedicineDepartment of Microbiology, The Ohio State University||The Center for RNA Biology, The Ohio State University
医学研究方法基础医学生物科学研究方法、生物科学研究技术
SARS-CoV-2 RdRpRNA synthesissynonymous codonsribosome pausing
Svetlov Vladimir,Wang Bing,Nudler Evgeny,Artsimovitch Irina.Lost in translation: codon optimization inactivates SARS-CoV-2 RdRp[EB/OL].(2025-03-28)[2025-04-30].https://www.biorxiv.org/content/10.1101/2021.01.24.428004.点此复制
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