Haruna Isiyaku Umar1,2, Bushra Siraj3,4, Adeola Ajayi5, Tajudeen O Jimoh6,7, Prosper Obed Chukwuemeka8. 1. Department of Biochemistry, School of Sciences, Federal University of Technology, Along Owo-Ilesha Express Way, P.M.B. 704, Akure, Ondo State, Nigeria. ariwajoye3@gmail.com. 2. Ioncure Tech Pvt. Ltd., Delhi, 110085, India. ariwajoye3@gmail.com. 3. Ioncure Tech Pvt. Ltd., Delhi, 110085, India. 4. Dr. Zafar H. Zaidi Center for Proteomics, University of Karachi, Karachi, Pakistan. 5. Department of Biochemistry, School of Sciences, Federal University of Technology, Along Owo-Ilesha Express Way, P.M.B. 704, Akure, Ondo State, Nigeria. 6. Faculty of Pharmaceutical Sciences, Department of Pharmacognosy and Pharmaceutical Botany, Chulalongkorn University, Bangkok, Thailand. 7. Department of Biochemistry, Habib Medical School, Islamic University in Uganda, P. O. Box 7689, Kampala, Uganda. 8. Department of Biotechnology, School of sciences, Federal University of Technology, Akure, Ondo State, Nigeria.
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.
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-19infectedpatients 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.
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