Modelling the active SARS-CoV-2 helicase complex as a basis for structure-based inhibitor design

Dénes Berta, Magd Badaoui, Pedro J. Buigues, Sam Alexander Martino, Andrei V. Pisliakov, Nadia Elghobashi-Meinhardt, Geoff Wells, Sarah A. Harris, Elisa Frezza, Edina Rosta (Lead / Corresponding author)

Research output: Contribution to specialist publicationArticle

Abstract

Having claimed over 1 million lives worldwide to date, the ongoing COVID-19 pandemic has created one of the biggest challenges to develop an effective drug to treat infected patients. Among all the proteins expressed by the virus, RNA helicase is a fundamental protein for viral replication, and it is highly conserved among the coronaviridae family. To date, there is no high-resolution structure of helicase bound with ATP and RNA. We present here structural insights and molecular dynamics (MD) simulation results of the SARS-CoV-2 RNA helicase both in its apo form and in complex with its natural substrates. Our structural information of the catalytically competent helicase complex provides valuable insights for the mechanism and function of this enzyme at the atomic level, a key to develop specific inhibitors for this potential COVID-19 drug target.
Original languageEnglish
Number of pages18
Specialist publicationBioRxiv
PublisherCold Spring Harbor Laboratory
DOIs
Publication statusPublished - 3 Nov 2020

Fingerprint Dive into the research topics of 'Modelling the active SARS-CoV-2 helicase complex as a basis for structure-based inhibitor design'. Together they form a unique fingerprint.

Cite this