Abstract
BackgroundThe 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. Results4-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. ConclusionThe 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.
Highlights
The World Health Organization has recently declared a new coronavirus disease (COVID-19) a pandemic and a global health emergency
This viral disease is caused by severe acute respiratory syndrome 2 (SARSCOV-2); a spherical-shaped, single-stranded, positively sensed Ribonucleic acid (RNA) virus with a genome size of approximately 30,000 base pairs consisting of about eleven open reading frames (ORFs) that encodes numerous proteins involved in the viral life cycle [2,3,4]
It is pertinent to note in this present in silico study, compounds were selected based on their pharmacological roles, large quantity in nature, and most significantly, had not been used for any study to evaluate them against the etiological agent of the recent coronavirus outbreak be it in silico, in vitro, nor in vivo
Summary
The World Health Organization has recently declared a new coronavirus disease (COVID-19) a pandemic and a global health emergency. The World Health Organization has declared the most recent coronavirus (COVID-19) a pandemic and a global emergency that causes a global outbreak since early this year after emerging from Wuhan, Hubei province of China in late December of 2019 [1, 2]. This viral disease is caused by severe acute respiratory syndrome 2 (SARSCOV-2); a spherical-shaped, single-stranded, positively sensed RNA virus with a genome size of approximately 30,000 base pairs consisting of about eleven open reading frames (ORFs) that encodes numerous proteins (structural and non-structural) involved in the viral life cycle [2,3,4]. Among these nsps are the papain-like protease (nsp3), main protease (nsp5), RNA-dependent RNA polymerase (RdRp/ nsp12), helicase (nsp13), and nsp (NendoU) which have been viewed to be viable antiviral drug targets [4, 5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
