Developing Rationally Designed Small Molecules to Inhibit SARS‐CoV‐2 Spike Protein‐Human ACE2 Receptor Interactions

ABSTRACT: Targeting the binding domain of SARS‐CoV‐2 spike protein (S protein) with rationally designed small molecules is expected to disrupt S protein‐human ACE2 (hACE2) interactions. First, we set out to establish a small molecule library using traditional structure‐based drug design strategies and various computational tools. Small molecule design began by utilizing FTMap to identify “hotspots” on the S protein binding domain (Chain B), which has been shown to interact with the hACE2 receptor (PDB file 6LZG). A hotspot was identified in the S protein‐hACE2 binding domain. Within the probe cluster for this hotspot, the phenol probe was found to have strong interactions with the surrounding amino acids and thus selected as the initial scaffold. Based on the residues surrounding the hotspot, additi

SUBMITTER: Dufresne J 

PROVIDER: S-EPMC8239575 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature