Bispidine-amino acid conjugates act as a novel scaffold for the design of antivirals that block Japanese encephalitis virus replication.
Japanese encephalitis virus (JEV) is a major cause of viral encephalitis in South and South-East Asia. Lack of antivirals and non-availability of affordable vaccines in these endemic areas are a major setback in combating JEV and other closely related viruses such as West Nile virus and dengue virus...
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ftdoajarticles:oai:doaj.org/article:43e05af414e744a5b3719a5616008a25 2023-05-15T15:13:17+02:00 Bispidine-amino acid conjugates act as a novel scaffold for the design of antivirals that block Japanese encephalitis virus replication. V Haridas Kullampalayam Shanmugam Rajgokul Sandhya Sadanandan Tanvi Agrawal Vats Sharvani M V S Gopalakrishna M B Bijesh Kanhaiya Lal Kumawat Anirban Basu Guruprasad R Medigeshi 2013-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0002005 https://doaj.org/article/43e05af414e744a5b3719a5616008a25 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3547849?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002005 https://doaj.org/article/43e05af414e744a5b3719a5616008a25 PLoS Neglected Tropical Diseases, Vol 7, Iss 1, p e2005 (2013) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2013 ftdoajarticles https://doi.org/10.1371/journal.pntd.0002005 2022-12-30T22:26:14Z Japanese encephalitis virus (JEV) is a major cause of viral encephalitis in South and South-East Asia. Lack of antivirals and non-availability of affordable vaccines in these endemic areas are a major setback in combating JEV and other closely related viruses such as West Nile virus and dengue virus. Protein secondary structure mimetics are excellent candidates for inhibiting the protein-protein interactions and therefore serve as an attractive tool in drug development. We synthesized derivatives containing the backbone of naturally occurring lupin alkaloid, sparteine, which act as protein secondary structure mimetics and show that these compounds exhibit antiviral properties.In this study we have identified 3,7-diazabicyclo[3.3.1]nonane, commonly called bispidine, as a privileged scaffold to synthesize effective antiviral agents. We have synthesized derivatives of bispidine conjugated with amino acids and found that hydrophobic amino acid residues showed antiviral properties against JEV. We identified a tryptophan derivative, Bisp-W, which at 5 µM concentration inhibited JEV infection in neuroblastoma cells by more than 100-fold. Viral inhibition was at a stage post-entry and prior to viral protein translation possibly at viral RNA replication. We show that similar concentration of Bisp-W was capable of inhibiting viral infection of two other encephalitic viruses namely, West Nile virus and Chandipura virus.We have demonstrated that the amino-acid conjugates of 3,7-diazabicyclo[3.3.1]nonane can serve as a molecular scaffold for development of potent antivirals against encephalitic viruses. Our findings will provide a novel platform to develop effective inhibitors of JEV and perhaps other RNA viruses causing encephalitis. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 7 1 e2005 |
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English |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 V Haridas Kullampalayam Shanmugam Rajgokul Sandhya Sadanandan Tanvi Agrawal Vats Sharvani M V S Gopalakrishna M B Bijesh Kanhaiya Lal Kumawat Anirban Basu Guruprasad R Medigeshi Bispidine-amino acid conjugates act as a novel scaffold for the design of antivirals that block Japanese encephalitis virus replication. |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Japanese encephalitis virus (JEV) is a major cause of viral encephalitis in South and South-East Asia. Lack of antivirals and non-availability of affordable vaccines in these endemic areas are a major setback in combating JEV and other closely related viruses such as West Nile virus and dengue virus. Protein secondary structure mimetics are excellent candidates for inhibiting the protein-protein interactions and therefore serve as an attractive tool in drug development. We synthesized derivatives containing the backbone of naturally occurring lupin alkaloid, sparteine, which act as protein secondary structure mimetics and show that these compounds exhibit antiviral properties.In this study we have identified 3,7-diazabicyclo[3.3.1]nonane, commonly called bispidine, as a privileged scaffold to synthesize effective antiviral agents. We have synthesized derivatives of bispidine conjugated with amino acids and found that hydrophobic amino acid residues showed antiviral properties against JEV. We identified a tryptophan derivative, Bisp-W, which at 5 µM concentration inhibited JEV infection in neuroblastoma cells by more than 100-fold. Viral inhibition was at a stage post-entry and prior to viral protein translation possibly at viral RNA replication. We show that similar concentration of Bisp-W was capable of inhibiting viral infection of two other encephalitic viruses namely, West Nile virus and Chandipura virus.We have demonstrated that the amino-acid conjugates of 3,7-diazabicyclo[3.3.1]nonane can serve as a molecular scaffold for development of potent antivirals against encephalitic viruses. Our findings will provide a novel platform to develop effective inhibitors of JEV and perhaps other RNA viruses causing encephalitis. |
format |
Article in Journal/Newspaper |
author |
V Haridas Kullampalayam Shanmugam Rajgokul Sandhya Sadanandan Tanvi Agrawal Vats Sharvani M V S Gopalakrishna M B Bijesh Kanhaiya Lal Kumawat Anirban Basu Guruprasad R Medigeshi |
author_facet |
V Haridas Kullampalayam Shanmugam Rajgokul Sandhya Sadanandan Tanvi Agrawal Vats Sharvani M V S Gopalakrishna M B Bijesh Kanhaiya Lal Kumawat Anirban Basu Guruprasad R Medigeshi |
author_sort |
V Haridas |
title |
Bispidine-amino acid conjugates act as a novel scaffold for the design of antivirals that block Japanese encephalitis virus replication. |
title_short |
Bispidine-amino acid conjugates act as a novel scaffold for the design of antivirals that block Japanese encephalitis virus replication. |
title_full |
Bispidine-amino acid conjugates act as a novel scaffold for the design of antivirals that block Japanese encephalitis virus replication. |
title_fullStr |
Bispidine-amino acid conjugates act as a novel scaffold for the design of antivirals that block Japanese encephalitis virus replication. |
title_full_unstemmed |
Bispidine-amino acid conjugates act as a novel scaffold for the design of antivirals that block Japanese encephalitis virus replication. |
title_sort |
bispidine-amino acid conjugates act as a novel scaffold for the design of antivirals that block japanese encephalitis virus replication. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2013 |
url |
https://doi.org/10.1371/journal.pntd.0002005 https://doaj.org/article/43e05af414e744a5b3719a5616008a25 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 7, Iss 1, p e2005 (2013) |
op_relation |
http://europepmc.org/articles/PMC3547849?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002005 https://doaj.org/article/43e05af414e744a5b3719a5616008a25 |
op_doi |
https://doi.org/10.1371/journal.pntd.0002005 |
container_title |
PLoS Neglected Tropical Diseases |
container_volume |
7 |
container_issue |
1 |
container_start_page |
e2005 |
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1766343863560044544 |