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Project

Hitting coronavirus replication in its core by combined inhibition of the nsp12 polymerase and associated proteins of the replication-transcription complex

The current COVID-19 vaccines do not prevent the appearance of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To treat infected risk groups and prepare against future zoonotic coronavirus (CoV) outbreaks, the development and stockpiling of pan-CoV therapeutics must be prioritized. In this project, we investigate a class of CoV lead inhibitors, recently identified in our laboratory and acting after onset of viral RNA synthesis. Our aim is to reveal their target, understand the role of this protein in CoV replication, and develop suitable pharmacophores for drug development. The project uses virological methods (such as resistance selection, evaluation against a broad panel of human and animal CoVs and minigenome assays), as well as biochemical assays with the CoV target protein obtained by recombinant expression. This includes structural (i.e. cryo-EM) and biophysical analysis of the drug-target interaction and the effect of our inhibitors on the dynamic structure of CoV replication-transcription complexes during subsequent stages in viral RNA synthesis.

Date:13 Sep 2021 →  Today
Keywords:coronavirus, inhibitor, replication, drug development, COVID-19
Disciplines:Virology, Non-clinical studies, Medicinal chemistry
Project type:PhD project