Tackling SARS‐CoV‐2: Deep Purpose Virtual Screening Identified Compounds to Target the Glycosylated Full‐Length GRP78

Abstract

AbstractThe glucose‐regulated protein 78 (GRP78) is pivotal in endoplasmic reticulum protein homeostasis and the unfolded protein response during cellular stress. Experimental validation has shown its role in SARS‐CoV‐2 attachment and entry. Here, the full GRP78 sequence, adding carbohydrate sugars to nucleotide‐binding domain sites, and conduct molecular dynamics simulations is modeled. Utilizing DeepPurpose virtual screening on the COCONUT database, followed by blind structure‐based screening with AutoDock Vina, top interacting binders is identified. Molecular dynamic simulations with MM/GBSA reveal stable binding of CNP0339053 and CNP0400762 to GRP78 (free energies of −43.5 ±6.7 and −34.8 ±3.9 kcal mol−1, respectively). These compounds hold promise as safe antiviral treatments for COVID‐19.