Alternatives Research & Development Foundation to Support Research on COVID-19, Aiming for Advancement in Non-animal Methods of Drug Discovery

By August 13, 2020 August 19th, 2020 News, Research

Pharmaceutical companies across the globe are racing to introduce clinically tested and approved therapeutic drugs that fight COVID-19 virus to market. As is typical in drug discovery research, animals have played a critical role in the development and testing of COVID-19 therapeutics. A proposal by U-M Professor Rudy J. Richardson, Dow Professor Emeritus of Toxicology, Professor Emeritus of Environmental Health Sciences, and Associate Professor Emeritus of Neurology at the University of Michigan, titled “Discovering host factor inhibitors in silico for SARS-CoV-2 entry and replication” has been awarded funding to identify compounds that bind to human proteins that facilitate entry and/or replication of the SARS-CoV-2 virus. Awarded, in part, because of its potential to develop alternative methods to advance science and replace or reduce animal use, this research will employ in silico ligand protein docking to discover existing drugs (repurposing) and/or new drug candidates capable of inhibiting host proteins involved in infection pathways for the COVID-19 virus, SARS-CoV-2.

Protein docking targets include four serine hydrolases. Using these targets, researchers will reversibly dock approximately 40,000 ligands from the Binding Database comprising FDA-approved drugs along with serine protease and PLA2 inhibitors, including organoboron compounds. Then, covalent docking will be conducted on a ligand subset containing pharmacophores capable of covalently binding serine hydrolases. Consensus ranking from four docking programs will be used to generate a penultimate list of candidate compounds. Those showing high predicted potency against off-target serine hydrolases will be excluded. The final list of compounds will be made publicly available for further evaluation in bioassays.

Professor Richardson’s grant, awarded by the Alternatives Research & Development Foundation, is a part of the ARDF’s 2020 Open Grants program, funding research projects that develop alternate methods to advance science and replace or reduce animal use. Although the immediate goal of this computational study supports the identification or development of a COVID-19 vaccine, the long-range vision is to advance computational and in vitro approaches to eliminate animal use from drug discovery for humans and other species. 

MICDE Affiliated Faculty member Rudy J. Richardson is a Dow Professor Emeritus of Toxicology and Professor Emeritus of Environmental Health Sciences within the School of Public Health, and Associate Professor Emeritus of Neurology within the Medical School at the University of Michigan.