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Molecular modelling studies unveil potential binding sites on human serum albumin for selected experimental and in silico COVID-19 drug candidate molecules

Human serum albumin (HSA) is the most prevalent protein in the blood plasma which binds an array of exogenous compounds. Drug binding to HSA is an important consideration when developing new therapeutic molecules, and it also aids in understanding the underlying mechanisms that govern their pharmaco...

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Autores principales: Gurung, Arun Bahadur, Ali, Mohammad Ajmal, Lee, Joongku, Farah, Mohammad Abul, Al-Anazi, Khalid Mashay, Sami, Hiba
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447726/
https://www.ncbi.nlm.nih.gov/pubmed/34548836
http://dx.doi.org/10.1016/j.sjbs.2021.09.042
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author Gurung, Arun Bahadur
Ali, Mohammad Ajmal
Lee, Joongku
Farah, Mohammad Abul
Al-Anazi, Khalid Mashay
Sami, Hiba
author_facet Gurung, Arun Bahadur
Ali, Mohammad Ajmal
Lee, Joongku
Farah, Mohammad Abul
Al-Anazi, Khalid Mashay
Sami, Hiba
author_sort Gurung, Arun Bahadur
collection PubMed
description Human serum albumin (HSA) is the most prevalent protein in the blood plasma which binds an array of exogenous compounds. Drug binding to HSA is an important consideration when developing new therapeutic molecules, and it also aids in understanding the underlying mechanisms that govern their pharmacological effects. This study aims to investigate the molecular binding of coronavirus disease 2019 (COVID-19) therapeutic candidate molecules to HSA and to identify their putative binding sites. Binding energies and interacting residues were used to evaluate the molecular interaction. Four drug candidate molecules (β-D-N4-hydroxycytidine, Chloroquine, Disulfiram, and Carmofur) demonstrate weak binding to HSA, with binding energies ranging from −5 to −6.7 kcal/mol. Ivermectin, Hydroxychloroquine, Remdesivir, Arbidol, and other twenty drug molecules with binding energies ranging from −6.9 to −9.5 kcal/mol demonstrated moderate binding to HSA. The strong HSA binding drug candidates consist of fourteen molecules (Saquinavir, Ritonavir, Dihydroergotamine, Daclatasvir, Paritaprevir etc.) with binding energies ranging from −9.7 to −12.1 kcal/mol. All these molecules bind to different HSA subdomains (IA, IB, IIA, IIB, IIIA, and IIIB) through molecular forces such as hydrogen bonds and hydrophobic interactions. Various pharmacokinetic properties (gastrointestinal absorption, blood-brain barrier permeation, P-glycoprotein substrate, and cytochrome P450 inhibitor) of each molecule were determined using SwissADME program. Further, the stability of the HSA-ligand complexes was analyzed through 100 ns molecular dynamics simulations considering various geometric properties. The binding free energy between free HSA and compounds were calculated using Molecular mechanics Poisson–Boltzmann surface area (MM/PBSA) and molecular mechanics generalized Born surface area (MM/GBSA) approach. The findings of this study might be useful in understanding the mechanism of COVID-19 drug candidates binding to serum albumin protein, as well as their pharmacodynamics and pharmacokinetics.
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spelling pubmed-84477262021-09-17 Molecular modelling studies unveil potential binding sites on human serum albumin for selected experimental and in silico COVID-19 drug candidate molecules Gurung, Arun Bahadur Ali, Mohammad Ajmal Lee, Joongku Farah, Mohammad Abul Al-Anazi, Khalid Mashay Sami, Hiba Saudi J Biol Sci Original Article Human serum albumin (HSA) is the most prevalent protein in the blood plasma which binds an array of exogenous compounds. Drug binding to HSA is an important consideration when developing new therapeutic molecules, and it also aids in understanding the underlying mechanisms that govern their pharmacological effects. This study aims to investigate the molecular binding of coronavirus disease 2019 (COVID-19) therapeutic candidate molecules to HSA and to identify their putative binding sites. Binding energies and interacting residues were used to evaluate the molecular interaction. Four drug candidate molecules (β-D-N4-hydroxycytidine, Chloroquine, Disulfiram, and Carmofur) demonstrate weak binding to HSA, with binding energies ranging from −5 to −6.7 kcal/mol. Ivermectin, Hydroxychloroquine, Remdesivir, Arbidol, and other twenty drug molecules with binding energies ranging from −6.9 to −9.5 kcal/mol demonstrated moderate binding to HSA. The strong HSA binding drug candidates consist of fourteen molecules (Saquinavir, Ritonavir, Dihydroergotamine, Daclatasvir, Paritaprevir etc.) with binding energies ranging from −9.7 to −12.1 kcal/mol. All these molecules bind to different HSA subdomains (IA, IB, IIA, IIB, IIIA, and IIIB) through molecular forces such as hydrogen bonds and hydrophobic interactions. Various pharmacokinetic properties (gastrointestinal absorption, blood-brain barrier permeation, P-glycoprotein substrate, and cytochrome P450 inhibitor) of each molecule were determined using SwissADME program. Further, the stability of the HSA-ligand complexes was analyzed through 100 ns molecular dynamics simulations considering various geometric properties. The binding free energy between free HSA and compounds were calculated using Molecular mechanics Poisson–Boltzmann surface area (MM/PBSA) and molecular mechanics generalized Born surface area (MM/GBSA) approach. The findings of this study might be useful in understanding the mechanism of COVID-19 drug candidates binding to serum albumin protein, as well as their pharmacodynamics and pharmacokinetics. Elsevier 2022-01 2021-09-17 /pmc/articles/PMC8447726/ /pubmed/34548836 http://dx.doi.org/10.1016/j.sjbs.2021.09.042 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Gurung, Arun Bahadur
Ali, Mohammad Ajmal
Lee, Joongku
Farah, Mohammad Abul
Al-Anazi, Khalid Mashay
Sami, Hiba
Molecular modelling studies unveil potential binding sites on human serum albumin for selected experimental and in silico COVID-19 drug candidate molecules
title Molecular modelling studies unveil potential binding sites on human serum albumin for selected experimental and in silico COVID-19 drug candidate molecules
title_full Molecular modelling studies unveil potential binding sites on human serum albumin for selected experimental and in silico COVID-19 drug candidate molecules
title_fullStr Molecular modelling studies unveil potential binding sites on human serum albumin for selected experimental and in silico COVID-19 drug candidate molecules
title_full_unstemmed Molecular modelling studies unveil potential binding sites on human serum albumin for selected experimental and in silico COVID-19 drug candidate molecules
title_short Molecular modelling studies unveil potential binding sites on human serum albumin for selected experimental and in silico COVID-19 drug candidate molecules
title_sort molecular modelling studies unveil potential binding sites on human serum albumin for selected experimental and in silico covid-19 drug candidate molecules
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447726/
https://www.ncbi.nlm.nih.gov/pubmed/34548836
http://dx.doi.org/10.1016/j.sjbs.2021.09.042
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