Examination of drug leads for binding to a novel homotrimer cavity formed by the SARS-CoV-2 spike glycoprotein

There is a high unmet clinical need to develop new anti-SARS-CoV2 (the virus that causes COVID-19 disease) therapeutics that can be used to treat the current (and likely to re-emerge) COVID-19 disease. Re-purposing existing drugs is a global priority as it provides a more rapid route to clinical studies. We have recently reported an in silico screen for the identification of drugs from an FDA approved library for the ability to bind to a novel drug binding site in the SARS-Cov2 spike protein (ref1; under revision). One of these FDA approved drug leads (Rapamycin) is already known to inhibit pathways that regulate ageing and our background data also shows that this compound can inhibit COV-229E infection in cell culture (see appendix form). We aim to screen a suite of approved drugs which are closely related to Rapamycin and novel in-house generated small molecule compounds optimized for targeting of this anti-ageing pathway to further identify and optimize drug leads that can inhibit the virus infection. The data output from the application will be used to start preclinical studies in animals, ex-vivo analysis using patient derived samples, and if successful into human clinical trials.