Discovery of potential inhibitors against New Delhi metallo-β-lactamase-1 from natural compounds: in silico-based methods

Abstract New Delhi metallo-β-lactamase variants and different types of metallo-β-lactamases have attracted enormous consideration for hydrolyzing almost all β-lactam antibiotics, which leads to multi drug resistance bacteria. Metallo-β-lactamases genes have disseminated in hospitals and all parts of...

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Autores principales:	Azhar Salari-jazi, Karim Mahnam, Parisa Sadeghi, Mohamad Sadegh Damavandi, Jamshid Faghri
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/83d7fbed1f264eeda67de2f509b53594
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spelling	oai:doaj.org-article:83d7fbed1f264eeda67de2f509b535942021-12-02T10:48:31ZDiscovery of potential inhibitors against New Delhi metallo-β-lactamase-1 from natural compounds: in silico-based methods10.1038/s41598-021-82009-62045-2322https://doaj.org/article/83d7fbed1f264eeda67de2f509b535942021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82009-6https://doaj.org/toc/2045-2322Abstract New Delhi metallo-β-lactamase variants and different types of metallo-β-lactamases have attracted enormous consideration for hydrolyzing almost all β-lactam antibiotics, which leads to multi drug resistance bacteria. Metallo-β-lactamases genes have disseminated in hospitals and all parts of the world and became a public health concern. There is no inhibitor for New Delhi metallo-β-lactamase-1 and other metallo-β-lactamases classes, so metallo-β-lactamases inhibitor drugs became an urgent need. In this study, multi-steps virtual screening was done over the NPASS database with 35,032 natural compounds. At first Captopril was extracted from 4EXS PDB code and use as a template for the first structural screening and 500 compounds obtained as hit compounds by molecular docking. Then the best ligand, i.e. NPC120633 was used as templet and 800 similar compounds were obtained. As a final point, ten compounds i.e. NPC171932, NPC100251, NPC18185, NPC98583, NPC112380, NPC471403, NPC471404, NPC472454, NPC473010 and NPC300657 had proper docking scores, and a 50 ns molecular dynamics simulation was performed for calculation binding free energy of each compound with New Delhi metallo-β-lactamase. Protein sequence alignment, 3D conformational alignment, pharmacophore modeling on all New Delhi metallo-β-lactamase variants and all types of metallo-β-lactamases were done. Quantum chemical perspective based on the fragment molecular orbital (FMO) method was performed to discover conserved and crucial residues in the catalytic activity of metallo-β-lactamases. These residues had similar 3D coordinates of spatial location in the 3D conformational alignment. So it is posibble that all types of metallo-β-lactamases can inhibit by these ten compounds. Therefore, these compounds were proper to mostly inhibit all metallo-β-lactamases in experimental studies.Azhar Salari-jaziKarim MahnamParisa SadeghiMohamad Sadegh DamavandiJamshid FaghriNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-20 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Azhar Salari-jazi Karim Mahnam Parisa Sadeghi Mohamad Sadegh Damavandi Jamshid Faghri Discovery of potential inhibitors against New Delhi metallo-β-lactamase-1 from natural compounds: in silico-based methods
description	Abstract New Delhi metallo-β-lactamase variants and different types of metallo-β-lactamases have attracted enormous consideration for hydrolyzing almost all β-lactam antibiotics, which leads to multi drug resistance bacteria. Metallo-β-lactamases genes have disseminated in hospitals and all parts of the world and became a public health concern. There is no inhibitor for New Delhi metallo-β-lactamase-1 and other metallo-β-lactamases classes, so metallo-β-lactamases inhibitor drugs became an urgent need. In this study, multi-steps virtual screening was done over the NPASS database with 35,032 natural compounds. At first Captopril was extracted from 4EXS PDB code and use as a template for the first structural screening and 500 compounds obtained as hit compounds by molecular docking. Then the best ligand, i.e. NPC120633 was used as templet and 800 similar compounds were obtained. As a final point, ten compounds i.e. NPC171932, NPC100251, NPC18185, NPC98583, NPC112380, NPC471403, NPC471404, NPC472454, NPC473010 and NPC300657 had proper docking scores, and a 50 ns molecular dynamics simulation was performed for calculation binding free energy of each compound with New Delhi metallo-β-lactamase. Protein sequence alignment, 3D conformational alignment, pharmacophore modeling on all New Delhi metallo-β-lactamase variants and all types of metallo-β-lactamases were done. Quantum chemical perspective based on the fragment molecular orbital (FMO) method was performed to discover conserved and crucial residues in the catalytic activity of metallo-β-lactamases. These residues had similar 3D coordinates of spatial location in the 3D conformational alignment. So it is posibble that all types of metallo-β-lactamases can inhibit by these ten compounds. Therefore, these compounds were proper to mostly inhibit all metallo-β-lactamases in experimental studies.
format	article
author	Azhar Salari-jazi Karim Mahnam Parisa Sadeghi Mohamad Sadegh Damavandi Jamshid Faghri
author_facet	Azhar Salari-jazi Karim Mahnam Parisa Sadeghi Mohamad Sadegh Damavandi Jamshid Faghri
author_sort	Azhar Salari-jazi
title	Discovery of potential inhibitors against New Delhi metallo-β-lactamase-1 from natural compounds: in silico-based methods
title_short	Discovery of potential inhibitors against New Delhi metallo-β-lactamase-1 from natural compounds: in silico-based methods
title_full	Discovery of potential inhibitors against New Delhi metallo-β-lactamase-1 from natural compounds: in silico-based methods
title_fullStr	Discovery of potential inhibitors against New Delhi metallo-β-lactamase-1 from natural compounds: in silico-based methods
title_full_unstemmed	Discovery of potential inhibitors against New Delhi metallo-β-lactamase-1 from natural compounds: in silico-based methods
title_sort	discovery of potential inhibitors against new delhi metallo-β-lactamase-1 from natural compounds: in silico-based methods
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/83d7fbed1f264eeda67de2f509b53594
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Discovery of potential inhibitors against New Delhi metallo-β-lactamase-1 from natural compounds: in silico-based methods

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