Molecular Docking and ADMET Prediction of Natural Compounds towards SARS Spike Glycoprotein-Human Angiotensin-Converting Enzyme 2 and SARS-CoV-2 Main Protease

Document Type : Original Articles

Authors

1 Department of Biological Sciences, McPherson University, Seriki Sotayo, Ogun, Nigeria

2 School of Pharmacy and Biomolecular Sciences, John Moores University, Liverpool, UK

Abstract

More than a decade ago, a novel coronavirus that infects humans, bats, and certain other mammals termed severe acute respiratory syndrome coronavirus (SARS-CoV) caused an epidemic with ~ 10% case fatality, creating global panic and economic damage. Recently, another strain of the virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), caused an infectious disease (COVID-19) in humans which was detected for the first time in Wuhan, China. Presently, there is no specific therapy available for the treatment of COVID-19. However, social distancing, patient isolation, and supportive medical care make up the current management for this current infectious disease pandemic. The present in silico study evaluated the binding affinities of some natural products (resveratrol, xylopic acid, ellagic acid, kaempferol, and quercetin) to human angiotensin-converting enzyme 2 and coronavirus (SARS-CoV-2) main protease compared to chloroquine, an inhibitor known to prevent cellular entry and replication of the coronavirus. The respective binding energies of the selected natural compounds and chloroquine towards the proteins were computed using PyRx virtual screening tool. The pharmacodynamic and pharmacokinetic attributes of the selected compounds were predicted using admetSAR. Molecular docking analysis showed that the natural compounds had better scores towards the selected protein compared to chloroquine with polar amino acid residues present at the binding sites. The predicted ADMET properties revealed the lower acute oral toxicity of the natural products compared to chloroquine. The study provides evidence suggesting that the relatively less toxic compounds from the natural sources could be repositioned as anti-viral agents to prevent the entry and replication of SARS-CoV-2.

Keywords

Main Subjects

Article Title [French]

Amarrage Moléculaire et Prédiction d'ADMET des Composés Naturels vers la Glycoprotéine de Pointe du SRAS-Enzyme de Conversion de l'angiotensine Humaine 2 et la Protéase Principale du SRAS-CoV-2

Abstract [French]

Il y a plus d'une décennie, un nouveau coronavirus qui infecte les humains, les chauves-souris et certains autres mammifères, appelé coronavirus du syndrome respiratoire aigu sévère (SRAS-CoV), a provoqué une épidémie avec environ 10% de fatalité, créant une panique mondiale et des dommages économiques. Récemment, une autre souche du virus, le coronavirus 2 du syndrome respiratoire aigu sévère (SRAS-CoV-2), a provoqué une maladie infectieuse (COVID-19) chez l'homme qui a été détectée pour la première fois à Wuhan, en Chine. Actuellement, il n'y a pas de thérapie spécifique disponible pour le traitement de COVID-19. Cependant, l'éloignement social, l'isolement des patients et les soins médicaux de soutienconstituent la gestion actuelle de cette pandémie actuelle de maladies infectieuses. La présente étude in silico a évalué les affinités de liaison de certains produits naturels (resvératrol, acide xylopique, acide ellagique, kaempférol et quercétine) à l'enzyme de conversion de l'angiotensine humaine 2 et à la principale protéase du coronavirus (SARS-CoV-2) par rapport à la chloroquine, un inhibiteur connu pour empêcher l'entrée cellulaire et la réplication du coronavirus. Les énergies de liaison respectives des composés naturels sélectionnés et de la chloroquine envers les protéines ont été calculées à l'aide de l'outil de criblage virtuel PyRx. Les attributs pharmacodynamiques et pharmacocinétiques des composés sélectionnés ont été prédits à l'aide d'admetSAR. L'analyse d'amarrage moléculaire a montré que les composés naturels avaient de meilleurs scores envers la protéine sélectionnée par rapport à la chloroquine avec des résidus d'acides aminés polaires présents sur les sites de liaison. Les propriétés ADMET prédites ont révélé la toxicité orale aiguë inférieure des produits naturels par rapport à la chloroquine. L'étude fournit des preuves suggérant que les composés relativement moins toxiques provenant de sources naturelles pourraient être repositionnés en tant qu'agents antiviraux pour empêcher l'entrée et la réplication du SRAS-CoV-2.

Keywords [French]

  • Chloroquine
  • covid-19
  • phytochimiques
  • amarrage moléculaire

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Archives of Razi Institute
Volume 76, Issue 3
September 2021
Pages 453-459

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