Journal Article


Interfering with mRNA methylation by the 2′O-Methyltransferase (NSP16) from SARS-CoV-2 to tackle the COVID-19 disease

Abstract

The pandemic associated to Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2) has resulted in a huge number of deaths and infected people. Although several vaccine programmes are currently underway and have reached phase 3, and a few small size drugs repurposed to aid treatment of severe cases of COVID-19 infections, effective therapeutic options for this disease do not currently exist. NSP16 is a S-adenosyl-L-Methionine (SAM) dependent 2′O-Methyltransferase that converts mRNA cap-0 into cap-1 structure to prevent virus detection by cell innate immunity mechanisms. NSP16 methylates the ribose 2′O-position of the first nucleotide of the mRNA only in the presence of an interacting partner, the protein NSP10. This feature suggests that inhibition of the NSP16 may represent a therapeutic window to treat COVID-19. To test this idea, we performed comparative structural analyses of the NSP16 present in human coronaviruses and developed a sinefungin (SFG) similarity-based virtual screening campaign to assess the druggability of the SARS-CoV-2 NSP16 enzyme. Through these studies, we identified the SFG analogue 44601604 as a promising more potent inhibitor of NSP16 to limit viral replication in infected cells, favouring viral clearance.

Attached files

Authors

Morales, Paula.
Curtis, Natalie L.
Zárate, Sandra G.
Bastida, Agatha
Bolanos-Garcia, Victor M.

Oxford Brookes departments

Department of Biological and Medical Sciences

Dates

Year of publication: 2020
Date of RADAR deposit: 2020-09-07


Creative Commons License This work is licensed under a Creative Commons Attribution 4.0 International License


Related resources

This RADAR resource is Identical to Interfering with mRNA methylation by the 2′O-Methyltransferase (NSP16) from SARS-CoV-2 to tackle the COVID-19 disease

Details

  • Owner: Joseph Ripp
  • Collection: Outputs
  • Version: 1 (show all)
  • Status: Live