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Neohesperidin and spike RBD interaction in omicron and its sub-variants: In silico, structural and simulation studies
COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged first around December 2019 in the city of Wuhan, China. Since then, several variants of the virus have emerged with different biological properties. This pandemic has so far led to widespread infection cycles wit...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Ltd.
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9721375/ https://www.ncbi.nlm.nih.gov/pubmed/36502697 http://dx.doi.org/10.1016/j.compbiomed.2022.106392 |
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author | Singh, Jaikee Kumar Dubey, Saumya Srivastava, Gaurava Siddiqi, Mohammad Imran Srivastava, Sandeep Kumar |
author_facet | Singh, Jaikee Kumar Dubey, Saumya Srivastava, Gaurava Siddiqi, Mohammad Imran Srivastava, Sandeep Kumar |
author_sort | Singh, Jaikee Kumar |
collection | PubMed |
description | COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged first around December 2019 in the city of Wuhan, China. Since then, several variants of the virus have emerged with different biological properties. This pandemic has so far led to widespread infection cycles with millions of fatalities and infections globally. In the recent cycle, a new variant omicron and its three sub-variants BA.1, BA.2 and BA.3 have emerged which seems to evade host immune defences and have brisk infection rate. Particularly, BA.2 variant has shown high transmission rate over BA.1 strain in different countries including India. In the present study, we have evaluated a set of eighty drugs/compounds using in silico docking calculations in omicron and its variants. These molecules were reported previously against SARS-CoV-2. Our docking and simulation analyses suggest differences in affinity of these compounds in omicron and BA.2 compared to SARS-CoV-2. These studies show that neohesperidin, a natural flavonoid found in Citrus aurantium makes a stable interaction with spike receptor domain of omicron and BA.2 compared to other variants. Free energy binding analyses further validates that neohesperidin forms a stable complex with spike RBD in omicron and BA.2 with a binding energy of −237.9 ± 18.7 kJ/mol and −164.1 ± 17.5 kJ/mol respectively. Key residual differences in the RBD interface of these variants form the basis for differential interaction affinities with neohesperidin as drug binding site overlaps with RBD-human ACE2 interface. These data might be useful for the design and development of novel scaffolds and pharmacophores to develop specific therapeutic strategies against these novel variants. |
format | Online Article Text |
id | pubmed-9721375 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-97213752022-12-06 Neohesperidin and spike RBD interaction in omicron and its sub-variants: In silico, structural and simulation studies Singh, Jaikee Kumar Dubey, Saumya Srivastava, Gaurava Siddiqi, Mohammad Imran Srivastava, Sandeep Kumar Comput Biol Med Article COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged first around December 2019 in the city of Wuhan, China. Since then, several variants of the virus have emerged with different biological properties. This pandemic has so far led to widespread infection cycles with millions of fatalities and infections globally. In the recent cycle, a new variant omicron and its three sub-variants BA.1, BA.2 and BA.3 have emerged which seems to evade host immune defences and have brisk infection rate. Particularly, BA.2 variant has shown high transmission rate over BA.1 strain in different countries including India. In the present study, we have evaluated a set of eighty drugs/compounds using in silico docking calculations in omicron and its variants. These molecules were reported previously against SARS-CoV-2. Our docking and simulation analyses suggest differences in affinity of these compounds in omicron and BA.2 compared to SARS-CoV-2. These studies show that neohesperidin, a natural flavonoid found in Citrus aurantium makes a stable interaction with spike receptor domain of omicron and BA.2 compared to other variants. Free energy binding analyses further validates that neohesperidin forms a stable complex with spike RBD in omicron and BA.2 with a binding energy of −237.9 ± 18.7 kJ/mol and −164.1 ± 17.5 kJ/mol respectively. Key residual differences in the RBD interface of these variants form the basis for differential interaction affinities with neohesperidin as drug binding site overlaps with RBD-human ACE2 interface. These data might be useful for the design and development of novel scaffolds and pharmacophores to develop specific therapeutic strategies against these novel variants. Elsevier Ltd. 2023-01 2022-12-05 /pmc/articles/PMC9721375/ /pubmed/36502697 http://dx.doi.org/10.1016/j.compbiomed.2022.106392 Text en © 2022 Elsevier Ltd. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Article Singh, Jaikee Kumar Dubey, Saumya Srivastava, Gaurava Siddiqi, Mohammad Imran Srivastava, Sandeep Kumar Neohesperidin and spike RBD interaction in omicron and its sub-variants: In silico, structural and simulation studies |
title | Neohesperidin and spike RBD interaction in omicron and its sub-variants: In silico, structural and simulation studies |
title_full | Neohesperidin and spike RBD interaction in omicron and its sub-variants: In silico, structural and simulation studies |
title_fullStr | Neohesperidin and spike RBD interaction in omicron and its sub-variants: In silico, structural and simulation studies |
title_full_unstemmed | Neohesperidin and spike RBD interaction in omicron and its sub-variants: In silico, structural and simulation studies |
title_short | Neohesperidin and spike RBD interaction in omicron and its sub-variants: In silico, structural and simulation studies |
title_sort | neohesperidin and spike rbd interaction in omicron and its sub-variants: in silico, structural and simulation studies |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9721375/ https://www.ncbi.nlm.nih.gov/pubmed/36502697 http://dx.doi.org/10.1016/j.compbiomed.2022.106392 |
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