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June 26, 2020 at 11:00AM EDT, At Home with Covid-19
by Brian Shoichet, an ISCB COVID-19 Webinar
The urgency of the coronavirus pandemic has motivated investigators world wide to seek approved drugs or investigation new drugs as a way to rapidly advance therapeutics into clinical trials to treat the disease. I will describe a large collaboration, hosted by the UCSF Quantitative Biology Institute, to do that in a mechanistically focused way. Using AP-MS, a host-pathogen network of viral and human proteins was created, and drugs were sought targeting the human partner. From among 322 high confidence human proteins associated with 26 viral proteins emerged 63 that were druggable. Against those, 69 drugs were tested for efficacy, and from these 10 drugs in two broad classes emerged: those targeting protein biogenesis, and those acting against the Sigma1 and Sigma2 receptors. The activities of these drugs, and the chemoinformatics infrastructure that supported their selection, will be discussed. The mechanism-based repurposing strategy will be compared to a complementary effort that targets viral proteins and seeks novel chemical matter, using structure-based ultra-large library docking.
*Access to the webinar series is complimentary for ISCB members. Nonmembers can join for a fee.
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