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Computational approach to study the synthesis of noscapine and potential of stereoisomers against nsP3 protease of CHIKV
Chikungunya fever is a major public health issue in India affecting millions of people and occurs due to Chikungunya. Chikungunya virus (CHIKV) is a single stranded RNA virus from the family of Togaviridae and genus alpha virus. It contain three structural proteins: glycosylated E1 and E2, embedded...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201138/ https://www.ncbi.nlm.nih.gov/pubmed/32382664 http://dx.doi.org/10.1016/j.heliyon.2019.e02795 |
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author | Singh, Prashant Kumar, Durgesh Vishvakarma, Vijay Kumar Yadav, Parul Jayaraj, Abhilash Kumari, Kamlesh |
author_facet | Singh, Prashant Kumar, Durgesh Vishvakarma, Vijay Kumar Yadav, Parul Jayaraj, Abhilash Kumari, Kamlesh |
author_sort | Singh, Prashant |
collection | PubMed |
description | Chikungunya fever is a major public health issue in India affecting millions of people and occurs due to Chikungunya. Chikungunya virus (CHIKV) is a single stranded RNA virus from the family of Togaviridae and genus alpha virus. It contain three structural proteins: glycosylated E1 and E2, embedded in the viral envelope, and a non-glycosylated nucleocapsid protein. Till date, researchers are working on inhibition of CHIKV but till now no cheap and effective medicine is available in the market. Therefore, the authors of this work thought of isoquinoline based noscapine to inhibit the nsP3 protease of CHIKV. The aim of the work is to understand the mechanism for the synthesis of noscapine theoretically using DFT. Further study the potential of all four isomers of noscapines {(13 (S,R), 14 (R,R), 15 (R,S) and 16 (S,S)} against nsP3 protease of CHIKV with the help of docking and MD simulation. The integrated e-pharmacophore binding affinity based virtual screening, docking and molecular dynamics simulation recognized four hits isomers as inhibition nsP3 protease of CHIKV. The docking energies of all the isomers of noscapine (13–16) with nsP3 protease CHIKV was found out to be more negative than baicalin (−8.06 kcal/mol) on selected sites. Amongst the isomers of noscapine, CMPD 13 possessed best binding affinity with four hydrogen bonding interactions. Further, ADME properties and blood-brain barrier permeability properties have been calculated. DFT studies of all the isomers of noscapine was investigated. |
format | Online Article Text |
id | pubmed-7201138 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-72011382020-05-07 Computational approach to study the synthesis of noscapine and potential of stereoisomers against nsP3 protease of CHIKV Singh, Prashant Kumar, Durgesh Vishvakarma, Vijay Kumar Yadav, Parul Jayaraj, Abhilash Kumari, Kamlesh Heliyon Article Chikungunya fever is a major public health issue in India affecting millions of people and occurs due to Chikungunya. Chikungunya virus (CHIKV) is a single stranded RNA virus from the family of Togaviridae and genus alpha virus. It contain three structural proteins: glycosylated E1 and E2, embedded in the viral envelope, and a non-glycosylated nucleocapsid protein. Till date, researchers are working on inhibition of CHIKV but till now no cheap and effective medicine is available in the market. Therefore, the authors of this work thought of isoquinoline based noscapine to inhibit the nsP3 protease of CHIKV. The aim of the work is to understand the mechanism for the synthesis of noscapine theoretically using DFT. Further study the potential of all four isomers of noscapines {(13 (S,R), 14 (R,R), 15 (R,S) and 16 (S,S)} against nsP3 protease of CHIKV with the help of docking and MD simulation. The integrated e-pharmacophore binding affinity based virtual screening, docking and molecular dynamics simulation recognized four hits isomers as inhibition nsP3 protease of CHIKV. The docking energies of all the isomers of noscapine (13–16) with nsP3 protease CHIKV was found out to be more negative than baicalin (−8.06 kcal/mol) on selected sites. Amongst the isomers of noscapine, CMPD 13 possessed best binding affinity with four hydrogen bonding interactions. Further, ADME properties and blood-brain barrier permeability properties have been calculated. DFT studies of all the isomers of noscapine was investigated. Elsevier 2019-12-24 /pmc/articles/PMC7201138/ /pubmed/32382664 http://dx.doi.org/10.1016/j.heliyon.2019.e02795 Text en © 2019 Published by Elsevier Ltd. http://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 | Article Singh, Prashant Kumar, Durgesh Vishvakarma, Vijay Kumar Yadav, Parul Jayaraj, Abhilash Kumari, Kamlesh Computational approach to study the synthesis of noscapine and potential of stereoisomers against nsP3 protease of CHIKV |
title | Computational approach to study the synthesis of noscapine and potential of stereoisomers against nsP3 protease of CHIKV |
title_full | Computational approach to study the synthesis of noscapine and potential of stereoisomers against nsP3 protease of CHIKV |
title_fullStr | Computational approach to study the synthesis of noscapine and potential of stereoisomers against nsP3 protease of CHIKV |
title_full_unstemmed | Computational approach to study the synthesis of noscapine and potential of stereoisomers against nsP3 protease of CHIKV |
title_short | Computational approach to study the synthesis of noscapine and potential of stereoisomers against nsP3 protease of CHIKV |
title_sort | computational approach to study the synthesis of noscapine and potential of stereoisomers against nsp3 protease of chikv |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201138/ https://www.ncbi.nlm.nih.gov/pubmed/32382664 http://dx.doi.org/10.1016/j.heliyon.2019.e02795 |
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