The COVID Moonshot: An open science collaboration to develop an orally bioavailable inhibitor of the SARS-CoV-2 main viral protease

Abstract: The COVID Moonshot [http://postera.ai/covid] is an open science collaboration aimed at developing a patent-free oral small molecule therapy for COVID-19 treatment and prophylaxis following exposure as rapidly as possible. Following the initial crystallization of the SARS-CoV-2 main viral protease (Mpro), a fragment screen conducted at Diamond Light Source / XChem identified an abundance of chemotypes completely covering the active site of Mpro. To leverage this data to rapidly develop potent inhibitors, an initial crowdsourcing campaign solicited molecular designs, and produced multiple potent covalent and non-covalent lead series. We will report on the subsequent medicinal chemistry optimization of several of the noncovalent lead series---assisted by Folding@home, which recently became the first distributed computing platform to cross the exaFLOP/s barrier---that has brought us very close to nominating a candidate for IND-enabling studies in preparation for clinical trials.

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