Structure-Based Design of Novel Peptidomimetics Targeting the SARS-CoV-2 Spike Protein

Abstract

Purpose: SARS-CoV-2 is a SARS-like novel coronavirus strain first identified in December 2019 in Wuhan, China. The virus has since spread globally, resulting in the current ongoing coronavirus disease 19 (COVID-19) pandemic. SARS-CoV-2 spike protein is a critical factor in the COVID-19 pathogenesis via interactions with the host cell angiotensin-converting enzyme 2 (ACE2) PD domain. Worldwide, numerous efforts are being made to combat COVID19. In the current study, we identified potential peptidomimetics against the SARS-CoV-2 spike protein. Methods: We utilized the information from ACE2-SARS-CoV-2 binary interactions, and based on crucial interacting interface residues, novel peptidomimetics were designed. Results: Top scoring peptidomimetics were found to bind at the ACE2 binding site of the receptor-binding domain (RBD) of SARS-CoV-2 spike protein. Conclusions: The current studies could pave the way for further investigations of these novel and potent compounds against the SARS-CoV-2.