Three-Dimensional Pharmacophore Modeling of Betulonic Acid Derivatives as a Strong Inhibitor of Human Coronavirus-229E Replication

Abstract

These-days, pharmacophore approaches have become one of the foremost tools in drug discovery after the past century’s development. Numerous ligand-based and structure-based strategies are developed for improved pharmacophore modeling with success and extensively applied in virtual screening, de novo design and lead improvement. Till now, there is little information on 3D-pharmacophore studies of 1,2,3-triazolo-fused betulonic acid derivatives as a strong inhibitor for human coronavirus-229E replication. Here, we tend to report the appliance of pharmacophore modeling for betulonic acid derivatives as an inhibitor. This study has been undertaken to realize intuitions into molecular mechanisms and structural necessities crucial for potential inhibition of betulonic acid derivatives. The standard procedure was adapted to develop the pharmacophoric models. It is found that the pharmacophore model of active betulonic acid derivative (compound 5h) unveils the importance of five- and six-member aliphatic cyclic hydrocarbon moiety, aromatic ring, –OH group of carboxylic acid, five-member heterocyclic rings (triazolo) and aliphatic alkene group and their correlation with the biological activity. It may be helpful within the design of novel betulonic acid derivatives inhibitors for human coronavirus-229E replication.\n\nKeywords: Pharmacophore Model, Antiviral activity, HCoV-229E replication, Betulonic acid derivatives, nsp15.