12.1 C
Saturday, June 3, 2023
HomeScienceInvestigating drug susceptibility to SARS-CoV-2 nuclear capsid protein interactions

Investigating drug susceptibility to SARS-CoV-2 nuclear capsid protein interactions


A hybrid structure determination approach demonstrates the interaction between the SARS-CoV-2 nucleocapsid and RNA-binding domains, and informs fragment screening to identify promising molecular scaffolds for drug development. credit: Nucleic acid research (2023). DOI: 10.1093/nar/gkad195

The groups of Alllain (IBC), Gossert (BNSP), and Leitner (IMSB) investigated the susceptibility of RNA interactions to the nucleocapsid protein of SARS-CoV-2 with a hybrid structure determination approach, which led to preliminary part results. Their findings have been published in Nucleic acid research.

Along with effective vaccines, antiviral compounds represent an essential approach to combating viral diseases. The D-BIOL groups led by Frédéric Allen, Alvar Gossert and Alexander Leitner investigated whether interactions between the SARS-CoV-2 nucleocapsid protein, which possesses two known RNA-binding domains, and sm2 RNA located in the 3’UTR of the SARS-CoV-2 nucleocapsid could be The cov-2 RNA is drug-worthy.

They chose a hybrid structural approach based on solution NMR and cross-linking MS experiments to rapidly obtain structural information on these complexes. This information was then used to generate constraints for building models of sm2-RNA complexes and the two RNA-binding domains of the nuclear capsid protein, for which previously unlinked structures were resolved. This approach resulted in the first model of how one RNA-binding domain interacts with RNA and expanded knowledge of the other RNA-binding domain.

An NMR-based fragment screen was then used to identify compounds bound to either protein or RNA domains in isolation. From these compounds, compounds that bind to the interaction interface of the respective molecules, which were known from hybrid structural approach models, were selected. Overall, the experiments revealed that these RNA–protein interactions appear to be treatable. Therefore, the identified compounds provide the basis for developing more effective molecules that block protein-RNA interactions.

more information:
Giacomo Padroni et al, A Hybrid Structure Determination Approach to Investigate the Treatability of a Nucleocapsid Protein for SARS-CoV-2, Nucleic acid research (2023). DOI: 10.1093/nar/gkad195

the quote: Retrieved 3 April 2023 from https://phys.org/news/2023-04-druggability-sars-cov-nucleocapsid-protein-rna: Investigating drug susceptibility of RNA-nucleocapsid interactions of SARS-CoV-2 (2023, 3 Apr).Programming Language

This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without written permission. The content is provided for informational purposes only.

The author of what'snew2day.com is dedicated to keeping you up-to-date on the latest news and information.

Latest stories