Bruno Canard - December 2, 2020

Bruno Canard, PhD, Senior Researcher, Viral Replication: Structure, Mechanisms, and Drug Design, CNRS-Aix Marseille University, France, "The outstanding SARS-CoV RNA synthesis machinery"

Dr. Canard’s group has been dedicated to learning more about viral replication mechanisms and in particular the cellular machinery used by coronaviruses for RNA replication. Coronaviruses have very large RNA genomes and Dr. Canard characterized Orb1a/1b as important for replication and transcription. Most recently, they have defined nsp12 (RdRp) as the main RNA-dependent RNA polymerase. They found that RdRp is very conserved between SARS-1 and SARS-2 with only one motif not conserved. Most of the changes are in external loops and suggests that most inhibitors of RNA polymerization should work for both viruses. They also found that Nsp12 requires Nsp7 and Nsp8 to form a replication complex and have extremely rapid polymerization. SARS-2 has almost ten times faster polymerization than most viruses at the expense of low fidelity. Dr. Canard’s group then used different nucleoside and nucleotide analogs to block RNA polymerization such as remdesivir, ribavirin, sofosbuvir and favipiravir as potential therapeutic options for coronavirus infection.