Since 2021, we have also focused on the study of possible ways of inhibiting the replication of SARS-CoV-2 viral RNA. Since SARS-CoV-2 encodes proteins that are involved in the repair mechanisms of mutations occuring during RNA replication, the use of nucleoside analogs as antivirals for the treatment of COVID-19 is highly restricted. Therefore, we focus on characterizing the potential allosteric inhibition of RNA-dependent RNA polymerase (RdRp) and screening the binding activity of small compounds that exhibit an inhibitory effect. Furthermore, we deal with the in vitro analysis of naturally occurring mutations in RdRp regions, the occurrence of which is related to different SARS-CoV-2 variants reported in the last three years for RdRp cofactors (nsp7, nsp8, and nsp12). Our other target is the exoribonuclease complex responsible for the repair activity of SARS-CoV-2 RNA replication. Inhibition of the activity of this complex, consisting of the exoribonuclease domain and its cofactor, appears as a promising approach to increase the efficacy of RdRp active site inhibitors.
Source: Glaunsinger Lab: Jessica M Tucker, Britt A Glaunsinger et al (Content Experts)
Grant supports: GAČR 2022-2024
Collaboration: Department of Biochemistry and Microbiology UCT Prague, IOCB CAS