Discovery of SARS-CoV-2 entry disruptors by targeting the spike protein
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In recent years, the design of protein-protein interaction (PPI) modulators has gradually attracted the attention of the field of computer-aided drug design. The specific physiological processes of interest can be modulated by using PPI interface disruptors or allosteric modulators to block protein-protein binding. Since 2020, COVID-19 has caused massive infections and deaths worldwide, with severe sequelae in even some of cured patients, severely affecting the quality of people’ lives. Through molecular simulations and virtual screening, we computationally predicted a series of PPI blockers targeting Spike proteins, including interfacial disruptors and allosteric modulators, and validated the anti-SARS-CoV-2 activity of these compounds through molecular and cellular-level experiments. Our study demonstrates the benefits of computer-aided drug design in PPI modulator design and provides a reference for the design and development of antiviral drugs for the treatment of COVID-19.