Overview

• Researchers at Harvard’s Wyss Institute combined physics-based molecular simulations with film-industry animation software and AI to map dynamic changes in the coronavirus Spike protein and identify a hidden S2 pocket.
• A computational screen of roughly 10,000 FDA-approved drugs highlighted bemcentinib as an initial oral antiviral candidate capable of locking the Spike protein in its pre-fusion state.
• Medicinal chemistry refinements produced WYS-694, an oral compound 12.5-fold more potent in binding the Spike pocket than its predecessor in antiviral assays.
• In prophylactic trials, oral dosing of WYS-694 in mice engineered with human ACE2 receptors reduced SARS-CoV-2 viral loads by over fourfold, whereas earlier leads failed to lower infection levels.
• WYS-694 also inhibited infection by SARS-CoV-1, MERS, and multiple SARS-CoV-2 variants in cell-based assays, signaling its potential as a broad-spectrum coronavirus treatment.