Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the COVID-19 pandemic. 2′-O-RNA methyltransferase (MTase) is one of the enzymes of this virus that is a potential target for antiviral therapy as it is crucial for RNA cap formation; an essential process for viral RNA stability. This MTase function is associated with the nsp16 protein, which requires a cofactor, nsp10, for its proper activity. Here we show the crystal structure of the nsp10-nsp16 complex bound to the pan-MTase inhibitor sinefungin in the active site. Our structural comparisons reveal low conservation of the MTase catalytic site between Zika and SARS-CoV-2 viruses, but high conservation of the MTase active site between SARS-CoV-2 and SARS-CoV viruses; these data suggest that the preparation of MTase inhibitors targeting several coronaviruses – but not flaviviruses – should be feasible. Together, our data add to important information for structure-based drug discovery. SARS-CoV-2 expresses a 2′-O RNA methyltransferase (MTase) that is involved in the viral RNA cap formation and therefore a target for antiviral therapy. Here the authors provide the structure of nsp10-nsp16 with the panMTase inhibitor sinefungin and report that the development of MTase inhibitor therapies that target multiple coronoaviruses is feasible.
【저자키워드】 SARS-CoV-2, X-ray crystallography, Antiviral agents, 【초록키워드】 antiviral therapy, coronavirus, therapy, Drug discovery, SARS-CoV, COVID-19 pandemic, virus, RNA, Protein, stability, methyltransferase, comparison, Zika, Viral RNA, inhibitor, information, cofactor, acute respiratory syndrome, enzyme, These data, complex, SARS-CoV-2 viruses, catalytic site, involved, coronavirus, feasible, expresse, RNA methyltransferase, 【제목키워드】 RNA, methyltransferase, Analysis, complex, involved, the SARS-CoV-2,