Molecular docking studies of some selected gallic acid derivatives against five non-structural proteins of novel coronavirus

Abstract

Background The World Health Organization has recently declared a new coronavirus disease (COVID-19) a pandemic and a global health emergency. The pressure to produce drugs and vaccines against the ongoing pandemic has resulted in the use of some drugs such as azithromycin, chloroquine (sulfate and phosphate), hydroxychloroquine, dexamethasone, favipiravir, remdesivir, ribavirin, ivermectin, and lopinavir/ritonavir. However, reports from some of the clinical trials with these drugs have proved detrimental on some COVID-19 infected patients with side effects more of which cardiomyopathy, cardiotoxicity, nephrotoxicity, macular retinopathy, and hepatotoxicity have been recently reported. Realizing the need for potent and harmless therapeutic compounds to combat COVID-19, we attempted in this study to find promising therapeutic compounds against the imminent threat of this virus. In this current study, 16 derivatives of gallic acid were docked against five selected non-structural proteins of SARS-COV-2 known to be a good target for finding small molecule inhibitors against the virus, namely, nsp3, nsp5, nsp12, nsp13, and nsp14. All the protein crystal structures and 3D structures of the small molecules (16 gallic acid derivatives and 3 control drugs) were retrieved from the Protein database (PDB) and PubChem server respectively. The compounds with lower binding energy than the control drugs were selected and subjected to pharmacokinetics screening using AdmetSAR server. Results 4-O-(6-galloylglucoside) gave binding energy values of − 8.4, − 6.8, − 8.9, − 9.1, and − 7.5 kcal/mol against Mpro, nsp3, nsp12, nsp13, and nsp15 respectively. Based on the ADMET profile, 4-O-(6-galloylglucoside) was found to be metabolized by the liver and has a very high plasma protein binding. Conclusion The result of this study revealed that 4-O-(6-galloylglucoside) could be a promising inhibitor against these SAR-Cov-2 proteins. However, there is still a need for further molecular dynamic simulation, in vivo and in vitro studies to support these findings.

Novel Molecules derived from 3-O-(6-galloylglucoside) inhibit Main Protease of SARS-CoV 2 In Silico

“…Authentication of molecular docking step is required through step validation as done earlier (Umar et al 2021a(Umar et al , 2021b to corroborate its exactitude and consistency. Our intent is to replicate the binding posture of a re-docked ligand of a protein that was co-crystallised alongside it.…”

“…PyRx 0.8, a suite integrated with Auto Dock Vina, was utilized for the molecular docking study. The specific target site for the receptor corresponding to the substrate-binding region was adjusted using the grid box with dimensions (18.08 × 26.45 × 26.30) Å, and the centre was attuned based on the site of substrate binding in the protein consisting of the following amino acids; Thr25, Thr26, His41, Cys44, Met49, Tyr54, Phe140, Leu141, Gly143, Cys145, Asn142, His163, His164, Met165, Ser144, Glu166, Pro168, His172, Val186, Asp187, Arg188, Gln189, Phe185, Thr190, and Gln192 (Dai et al 2020;Jin et al 2020;Umar et al 2021a). The compounds with docking score similar to that of the Seed molecule and control drug at the end of the experiment, were subjected to molecular interaction analysis with the aid of PyMOL© Molecular Graphics (version 2.4, 2016, Shrodinger LLC) and LigPlot + (Laskowski and Swindells 2011).…”

“…Additionally, the role it plays in the replication and proliferation of SARS-CoV 2 cannot be silenced. The process of discovering and developing drugs is time-consuming and cost-effective, thus the need for the use of computer-aided therapeutic discovery (CATD) which embraces structurebased, system-based and ligand-based therapeutic design (Dai et al 2020;Romano and Tatonetti 2019;Prieto-martı et al 2019;Umar et al 2021a). Today, the key roles played by computational methods in therapeutic design, discovery and development expedition cannot be overemphasized because of its numerous dimensional usage for assemblage of data, processing it before evaluation and interpretation (Dai et al 2020;Romano and Tatonetti 2019;Prieto-martı et al 2019;Umar et al 2021a).…”

“…From our erstwhile computational study, we showed that 3-O-(6-galloylglucoside) serves as potential inhibitor of SARS-CoV 2's main protease. However, this compound was found to have poor druglike properties that might affect it down the drug discovery pipeline even though it showed a good binding score with main protease of SARS-CoV 2 (Umar et al 2021a). In this current study, we designed 100 novel molecules through an artificial neural network-driven platform called LigDream (https:// playm olecu le.…”

Chemical constituents from Limonium tubiflorum and their in silico evaluation as potential antiviral agents against SARS-CoV-2

“…18 Also, gallic acid derivatives such as epigallocatechin gallate and (À)-epicatechin 3-O-(3 0 -O-methyl) gallate proposed to have inhibitory activity against coronavirus proteins. 15,20 Herein, our work is considered as the rst study aims to identify the chemical constituents of L. tubiorum aerial parts (leaves & stem) growing in the Northwestern coast, Egypt as well as its isolated phytochemicals (especially those have galloyl substructure of myricetin 3-O-glycoside derivatives) were assessed for the binding affinity with an in silico study against two important SARS-CoV-2 protein targets; main protease (M pro ) and Spike Glycoprotein.…”