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Despite the availability of vaccines, there remains a need for safe and effective antiviral drugs against coronaviruses to treat vulnerable patients, control transmission, and prepare for future outbreaks. In the spring of 2020, our lab was part of a global race to the 3D structure of the coronavirus SARS-Cov2 RNA-dependent RNA polymerase and provided mechanistic insights into viral RNA replication. We later also used structure-function studies to reveal the mechanisms of antiviral drugs such as remdesivir and molnupiravir, revealing key limitations in their efficacy and safety. Building on this framework, we are identifying novel polymerase inhibitors through large-scale chemical screening, in the hope to uncover leads for the development of next-generation antiviral therapies.

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