Structure-based drug discovery to identify SARS-CoV2 spike protein-ACE2 interaction inhibitors
Structure-based drug discovery to identify SARS-CoV2 spike protein-ACE2 interaction inhibitors
After the emergence of the COVID-19 pandemic in late 2019, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has undergone a dynamic evolution driven by the acquisition of genetic modifications, resulting in several variants that are further classified as variants of interest (VOIs), variants under monitoring (VUM) and variants of concern (VOC) by World Health Organization (WHO). Currently, there are five SARS-CoV-2 VOCs (Alpha, Beta, Delta, Gamma and Omicron), two VOIs (Lambda and Mu) and several other VOIs that have been reported globally. In this study, we report a natural compound, Curcumin, as the potential inhibitor to the interactions between receptor binding domain (RBD(S1)) and human angiotensin-converting enzyme 2 (hACE2) domains and showcased its inhibitory potential for the Delta and Omicron variants through a computational approach by implementing state of the art methods. The study for the first time revealed a higher efficiency of Curcumin, especially for hindering the interaction between RBD(S1) and hACE-2 domains of Delta and Omicron variants as compared to other lead compounds. We investigated that the mutations in the RBD(S1) of VOC especially Delta and Omicron variants affect its structure compared to that of the wild type and other variants and therefore altered its binding to the hACE2 receptor. Molecular docking and molecular dynamics (MD) simulation analyses substantially supported the findings in terms of the stability of the docked complexes. This study offers compelling evidence, warranting a more in-depth exploration into the impact of these alterations on the binding of identified drug molecules with the Spike protein. Further investigation into their potential therapeutic effects in vivo is highly recommended.
Angiotensin-Converting Enzyme 2/metabolism, Antiviral Agents/pharmacology, Binding Sites, COVID-19 Drug Treatment, COVID-19/virology, Curcumin/chemistry, Drug Discovery/methods, Humans, Molecular Docking Simulation, Molecular Dynamics Simulation, Protein Binding, SARS-CoV-2/drug effects, Spike Glycoprotein, Coronavirus/chemistry
3652-3670
Kant, Ravi
7701bda0-8d8b-4c7b-b988-75f6da612e2a
Kaushik, Rahul
adec7cab-74bd-4ff9-ad9d-3757512efc23
Chopra, Madhu
a7faf3c3-200c-42fd-991c-77a03de223fd
Saluja, Daman
c632b624-e87e-4d82-a045-5e3af0dd8439
1 April 2025
Kant, Ravi
7701bda0-8d8b-4c7b-b988-75f6da612e2a
Kaushik, Rahul
adec7cab-74bd-4ff9-ad9d-3757512efc23
Chopra, Madhu
a7faf3c3-200c-42fd-991c-77a03de223fd
Saluja, Daman
c632b624-e87e-4d82-a045-5e3af0dd8439
Kant, Ravi, Kaushik, Rahul, Chopra, Madhu and Saluja, Daman
(2025)
Structure-based drug discovery to identify SARS-CoV2 spike protein-ACE2 interaction inhibitors.
Journal of Biomolecular Structure and Dynamics, 43 (7), .
(doi:10.1080/07391102.2023.2300060).
Abstract
After the emergence of the COVID-19 pandemic in late 2019, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has undergone a dynamic evolution driven by the acquisition of genetic modifications, resulting in several variants that are further classified as variants of interest (VOIs), variants under monitoring (VUM) and variants of concern (VOC) by World Health Organization (WHO). Currently, there are five SARS-CoV-2 VOCs (Alpha, Beta, Delta, Gamma and Omicron), two VOIs (Lambda and Mu) and several other VOIs that have been reported globally. In this study, we report a natural compound, Curcumin, as the potential inhibitor to the interactions between receptor binding domain (RBD(S1)) and human angiotensin-converting enzyme 2 (hACE2) domains and showcased its inhibitory potential for the Delta and Omicron variants through a computational approach by implementing state of the art methods. The study for the first time revealed a higher efficiency of Curcumin, especially for hindering the interaction between RBD(S1) and hACE-2 domains of Delta and Omicron variants as compared to other lead compounds. We investigated that the mutations in the RBD(S1) of VOC especially Delta and Omicron variants affect its structure compared to that of the wild type and other variants and therefore altered its binding to the hACE2 receptor. Molecular docking and molecular dynamics (MD) simulation analyses substantially supported the findings in terms of the stability of the docked complexes. This study offers compelling evidence, warranting a more in-depth exploration into the impact of these alterations on the binding of identified drug molecules with the Spike protein. Further investigation into their potential therapeutic effects in vivo is highly recommended.
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More information
Accepted/In Press date: 13 December 2023
e-pub ahead of print date: 4 January 2024
Published date: 1 April 2025
Additional Information:
Publisher Copyright:
© 2024 Informa UK Limited, trading as Taylor & Francis Group.
Keywords:
Angiotensin-Converting Enzyme 2/metabolism, Antiviral Agents/pharmacology, Binding Sites, COVID-19 Drug Treatment, COVID-19/virology, Curcumin/chemistry, Drug Discovery/methods, Humans, Molecular Docking Simulation, Molecular Dynamics Simulation, Protein Binding, SARS-CoV-2/drug effects, Spike Glycoprotein, Coronavirus/chemistry
Identifiers
Local EPrints ID: 501549
URI: http://eprints.soton.ac.uk/id/eprint/501549
ISSN: 0739-1102
PURE UUID: e79210de-b035-49df-afd7-df691209b358
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Date deposited: 03 Jun 2025 16:58
Last modified: 04 Jun 2025 02:13
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Contributors
Author:
Ravi Kant
Author:
Rahul Kaushik
Author:
Madhu Chopra
Author:
Daman Saluja
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