Computational design of ultrashort peptide inhibitors of the receptor-binding domain of the SARS-CoV-2 S protein

Abstract Targeting the interaction between severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2)-receptor-binding domain (RBD) and angiotensin-converting enzyme (ACE2) is believed to be an effective strategy for drug design inhibit infection of SARS-CoV-2. Herein, several ultrashort peptidase inhibitors against RBD–ACE2 were obtained by a computer-aided approach based on RBD-binding residues protease (PD) ACE2. The designed peptides tested model coronavirus GX_P2V, which has 92.2 86% amino acid identity SARS-CoV-2 spike protein RBD, respectively. Molecular dynamics simulations binding free energy analysis predicted potential pocket RBD protein, this was confirmed specifically SI5? SI5?-b. They have only seven residues, showing potent antiviral activity low cytotoxicity. Enzyme-linked immunosorbent assay result also their inhibitory ability interaction. are promising precursor molecules development Corona Virus Disease 2019, novel may helpful or antibodies