Virtual Screening FDA Approved Drugs against Multiple Targets of SARS‐CoV‐2

Liang, Hualou; Zhao, Liang; Gong, Xiajing; Hu, Meng; Wang, Hongbin

The outbreak of the novel coronavirus SARS‐CoV‐2, the causative agent of COVID‐19 respiratory disease, leads to a global pandemic with high morbidity and mortality. Despite frenzied efforts in therapeutic development, there are currently no effective drugs for treatment, nor are there vaccines for its prevention. Drug repurposing, representing as an effective drug discovery strategy from existing drugs, is one of the most practical treatment options against the outbreak. In this study, we present a novel strategy for in‐silico molecular modeling screening for potential drugs that may interact with multiple main proteins of SARS‐CoV‐2. Targeting multiple viral proteins is a novel drug discovery concept in that it enables the potential drugs to act on different stages of the virus' life cycle, thereby potentially maximizing the drug potency. We screened 2,631 FDA‐approved small molecules against four key proteins of SARS‐CoV‐2 that are known as attractive targets for anti‐viral drug development. In total, we identified 29 drugs that could actively interact with two or more target proteins, with 5 drugs (Avapritinib, Bictegravir, Ziprasidone, Capmatinib and Pexidartinib) being common candidates for all four key host proteins and 3 of them possessing the desirable molecular properties. By overlaying docked positions of drug candidates onto individual host proteins, it has been further confirmed that the binding site conformations are conserved. The drugs identified in our screening provide potential guidance for experimental confirmation such as in vitro molecular assays, in vivo animal testing as well as incorporation into ongoing clinical studies.