Promising terpenes as SARS-CoV-2 spike receptor-binding domain (RBD) attachment inhibitors to the human ACE2 receptor: Integrated computational approach

Abstract

The spike protein receptor binding domain (S-RBD) is a necessary corona-viral protein for binding and entry of coronaviruses (COVs) into the host cells. Hence, it has emerged as an attractive antiviral drug target. Therefore, present study was aimed to target severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S-RBD with novel bioactive compounds to retrieve potential candidates that could serve as anti-coronavirus disease 2019 (COVID-19) drugs. In this paper, computational approaches were employed, especially the structure-based virtual screening followed by molecular dynamics (MD) simulation as well as binding energy analysis for the computational identification of specific terpenes from the medicinal plants, which can block SARS-CoV-2 S-RBD binding to Human angiotensin-converting enzyme 2 (H-ACE2) and can act as potent anti-COVID-19 drugs after further advancements. The screening of focused terpenes inhibitors database composed of ~1000 compounds with reported therapeutic potential resulted in the identification of three candidate compounds, NPACT01552, NPACT01557 and NPACT00631. These three compounds established conserved interactions, which were further explored through all-atom MD simulations, free energy calculations, and a residual energy contribution estimated by MM-PB( GB )SA method. All these compounds showed stable conformation and interacted well with the hot-spot residues of SARS-CoV-2 S-RBD. Conclusively, the reported SARS-CoV-2 S-RBD specific terpenes could serve as seeds for developing potent anti-COVID-19 drugs. Importantly, the experimentally tested glycyrrhizin (NPACT00631) against SARS-CoV could be used further in the fast-track drug development process to help curb COVID-19.

Cheminformatics-Based Identification of Potential Novel Anti-SARS-CoV-2 Natural Compounds of African Origin

“…Generally, the unbound RBD structures had the highest RMSD values ( Figure 6 a). A recent molecular dynamics study of RBD and terpene compounds reported a similar RMSD range of 0.08 and 0.25 nm [ 99 ].…”

An update review of emerging small-molecule therapeutic options for COVID-19

“…This discovery is of great significance for pharmacological and pharmacodynamic studies of drug combinations. Phytochemicals, such as flavonoids, isatins, and terpenoids, which exert recognized curative effects against SARS-CoV-2 infection, might be used in many people owing to their safety, low pharmacological side effects and availability [ 121 , 122 ]. However, the targets and mechanisms of action of several drug candidates remain unclear.…”

Pinpointing the potential hits for hindering interaction of SARS-CoV-2 S-protein with ACE2 from the pool of antiviral phytochemicals utilizing molecular docking and molecular dynamics (MD) simulations

“…S-protein is additionally focused with the most ordinarily discovered phytochemicals, where Kaempferol, Quercetin, and Fisetin had been appeared to bind and block the RBD which is validated utilizing molecular docking and MD reenactments [ 45 ]. Terpenes from plant sources like Trevesia Palmata , Aralia Dasyphylla and Glycyrrhiza glabra have shown the potentials to block and mask the RBD using computational methods is reported [ 46 ]. In another study, Epigallocatechingallate, Curcumin, Apigenin and Chrysophanol were identified to be potential hits possessing ability to serve as RBD blockers [ 47 ].…”