High Throughput Virtual Screening to Discover Inhibitors of the Main Protease of the Coronavirus SARS-CoV-2

• DOI: 10.20944/preprints202004.0161.v1
• Publication Date: 2020-04-09T14:12:17Z
• Authors: Birgit Strodel; Olujide Olubiyi; Maryam Olagunju; Monika Keutmann; Jennifer Loschwitz
• Keywords: Docking (animal); Indinavir; Natural product; Drug Design; Coronavirus

We use state-of-the-art computer-aided drug design (CADD) techniques to identify prospective inhibitors of the main protease enzyme, Mpro COVID-19 virus. With high-resolution X-ray crystallography structure this viral enzyme recently being solved, CADD provides a veritable tool for rapidly screening diverse sets compounds with aim identifying ligands capable forming energetically favorable complexes . From our 1,082,653 derived from ZINC, DrugBank, and in-house African natural product libraries, rescreening protocol incorporating dynamics via ensemble docking, we have been able range inhibitors, which include FDA-approved drugs, candidates in clinical trials, as well products. The top-ranking are characterized by presence an extended ring system combined functional groups that allow adapt flexibly active site as, example, present biflavonoid amentoflavone, one most promising identified here. This particular chemical architecture leads considerable stronger binding than found reference vitro demonstrated M pro inhibition anticoronavirus activity. determined work thus represent good starting point SARS-CoV-2 replication.