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Molecular Dynamic Simulation Search for Possible Amphiphilic Drug Discovery for Covid-19

To determine whether quaternary ammonium (k21) binds to Severe Acute Respiratory Syndrome–Coronavirus 2 (SARS-CoV-2) spike protein via computational molecular docking simulations, the crystal structure of the SARS-CoV-2 spike receptor-binding domain complexed with ACE-2 (PDB ID: 6LZG) was downloaded...

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Autores principales: Daood, Umer, Gopinath, Divya, Pichika, Malikarjuna Rao, Mak, Kit-Kay, Seow, Liang Lin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069104/
https://www.ncbi.nlm.nih.gov/pubmed/33921378
http://dx.doi.org/10.3390/molecules26082214
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author Daood, Umer
Gopinath, Divya
Pichika, Malikarjuna Rao
Mak, Kit-Kay
Seow, Liang Lin
author_facet Daood, Umer
Gopinath, Divya
Pichika, Malikarjuna Rao
Mak, Kit-Kay
Seow, Liang Lin
author_sort Daood, Umer
collection PubMed
description To determine whether quaternary ammonium (k21) binds to Severe Acute Respiratory Syndrome–Coronavirus 2 (SARS-CoV-2) spike protein via computational molecular docking simulations, the crystal structure of the SARS-CoV-2 spike receptor-binding domain complexed with ACE-2 (PDB ID: 6LZG) was downloaded from RCSB PD and prepared using Schrodinger 2019-4. The entry of SARS-CoV-2 inside humans is through lung tissues with a pH of 7.38–7.42. A two-dimensional structure of k-21 was drawn using the 2D-sketcher of Maestro 12.2 and trimmed of C18 alkyl chains from all four arms with the assumption that the core moiety k-21 was without C18. The immunogenic potential of k21/QA was conducted using the C-ImmSim server for a position-specific scoring matrix analyzing the human host immune system response. Therapeutic probability was shown using prediction models with negative and positive control drugs. Negative scores show that the binding of a quaternary ammonium compound with the spike protein’s binding site is favorable. The drug molecule has a large Root Mean Square Deviation fluctuation due to the less complex geometry of the drug molecule, which is suggestive of a profound impact on the regular geometry of a viral protein. There is high concentration of Immunoglobulin M/Immunoglobulin G, which is concomitant of virus reduction. The proposed drug formulation based on quaternary ammonium to characterize affinity to the SARS-CoV-2 spike protein using simulation and computational immunological methods has shown promising findings.
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spelling pubmed-80691042021-04-26 Molecular Dynamic Simulation Search for Possible Amphiphilic Drug Discovery for Covid-19 Daood, Umer Gopinath, Divya Pichika, Malikarjuna Rao Mak, Kit-Kay Seow, Liang Lin Molecules Article To determine whether quaternary ammonium (k21) binds to Severe Acute Respiratory Syndrome–Coronavirus 2 (SARS-CoV-2) spike protein via computational molecular docking simulations, the crystal structure of the SARS-CoV-2 spike receptor-binding domain complexed with ACE-2 (PDB ID: 6LZG) was downloaded from RCSB PD and prepared using Schrodinger 2019-4. The entry of SARS-CoV-2 inside humans is through lung tissues with a pH of 7.38–7.42. A two-dimensional structure of k-21 was drawn using the 2D-sketcher of Maestro 12.2 and trimmed of C18 alkyl chains from all four arms with the assumption that the core moiety k-21 was without C18. The immunogenic potential of k21/QA was conducted using the C-ImmSim server for a position-specific scoring matrix analyzing the human host immune system response. Therapeutic probability was shown using prediction models with negative and positive control drugs. Negative scores show that the binding of a quaternary ammonium compound with the spike protein’s binding site is favorable. The drug molecule has a large Root Mean Square Deviation fluctuation due to the less complex geometry of the drug molecule, which is suggestive of a profound impact on the regular geometry of a viral protein. There is high concentration of Immunoglobulin M/Immunoglobulin G, which is concomitant of virus reduction. The proposed drug formulation based on quaternary ammonium to characterize affinity to the SARS-CoV-2 spike protein using simulation and computational immunological methods has shown promising findings. MDPI 2021-04-12 /pmc/articles/PMC8069104/ /pubmed/33921378 http://dx.doi.org/10.3390/molecules26082214 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Daood, Umer
Gopinath, Divya
Pichika, Malikarjuna Rao
Mak, Kit-Kay
Seow, Liang Lin
Molecular Dynamic Simulation Search for Possible Amphiphilic Drug Discovery for Covid-19
title Molecular Dynamic Simulation Search for Possible Amphiphilic Drug Discovery for Covid-19
title_full Molecular Dynamic Simulation Search for Possible Amphiphilic Drug Discovery for Covid-19
title_fullStr Molecular Dynamic Simulation Search for Possible Amphiphilic Drug Discovery for Covid-19
title_full_unstemmed Molecular Dynamic Simulation Search for Possible Amphiphilic Drug Discovery for Covid-19
title_short Molecular Dynamic Simulation Search for Possible Amphiphilic Drug Discovery for Covid-19
title_sort molecular dynamic simulation search for possible amphiphilic drug discovery for covid-19
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069104/
https://www.ncbi.nlm.nih.gov/pubmed/33921378
http://dx.doi.org/10.3390/molecules26082214
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