Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Singh, Prashant, Kumar, Durgesh, Vishvakarma, Vijay Kumar, Yadav, Parul, Jayaraj, Abhilash, Kumari, Kamlesh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
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
_version_ 1783529484897484800
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
work_keys_str_mv AT singhprashant computationalapproachtostudythesynthesisofnoscapineandpotentialofstereoisomersagainstnsp3proteaseofchikv
AT kumardurgesh computationalapproachtostudythesynthesisofnoscapineandpotentialofstereoisomersagainstnsp3proteaseofchikv
AT vishvakarmavijaykumar computationalapproachtostudythesynthesisofnoscapineandpotentialofstereoisomersagainstnsp3proteaseofchikv
AT yadavparul computationalapproachtostudythesynthesisofnoscapineandpotentialofstereoisomersagainstnsp3proteaseofchikv
AT jayarajabhilash computationalapproachtostudythesynthesisofnoscapineandpotentialofstereoisomersagainstnsp3proteaseofchikv
AT kumarikamlesh computationalapproachtostudythesynthesisofnoscapineandpotentialofstereoisomersagainstnsp3proteaseofchikv