Cargando…
A Comprehensive Computational Investigation into the Conserved Virulent Proteins of Shigella species Unveils Potential Small-Interfering RNA Candidates as a New Therapeutic Strategy against Shigellosis
Shigella species account for the second-leading cause of deaths due to diarrheal diseases among children of less than 5 years of age. The emergence of multi-drug-resistant Shigella isolates and the lack of availability of Shigella vaccines have led to the pertinence in the efforts made for the devel...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8950558/ https://www.ncbi.nlm.nih.gov/pubmed/35335300 http://dx.doi.org/10.3390/molecules27061936 |
_version_ | 1784675170161524736 |
---|---|
author | Palit, Parag Chowdhury, Farhana Tasnim Baruah, Namrata Sarkar, Bonoshree Mou, Sadia Noor Kamal, Mehnaz Siddiqua, Towfida Jahan Noor, Zannatun Ahmed, Tahmeed |
author_facet | Palit, Parag Chowdhury, Farhana Tasnim Baruah, Namrata Sarkar, Bonoshree Mou, Sadia Noor Kamal, Mehnaz Siddiqua, Towfida Jahan Noor, Zannatun Ahmed, Tahmeed |
author_sort | Palit, Parag |
collection | PubMed |
description | Shigella species account for the second-leading cause of deaths due to diarrheal diseases among children of less than 5 years of age. The emergence of multi-drug-resistant Shigella isolates and the lack of availability of Shigella vaccines have led to the pertinence in the efforts made for the development of new therapeutic strategies against shigellosis. Consequently, designing small-interfering RNA (siRNA) candidates against such infectious agents represents a novel approach to propose new therapeutic candidates to curb the rampant rise of anti-microbial resistance in such pathogens. In this study, we analyzed 264 conserved sequences from 15 different conserved virulence genes of Shigella sp., through extensive rational validation using a plethora of first-generation and second-generation computational algorithms for siRNA designing. Fifty-eight siRNA candidates were obtained by using the first-generation algorithms, out of which only 38 siRNA candidates complied with the second-generation rules of siRNA designing. Further computational validation showed that 16 siRNA candidates were found to have a substantial functional efficiency, out of which 11 siRNA candidates were found to be non-immunogenic. Finally, three siRNA candidates exhibited a sterically feasible three-dimensional structure as exhibited by parameters of nucleic acid geometry such as: the probability of wrong sugar puckers, bad backbone confirmations, bad bonds, and bad angles being within the accepted threshold for stable tertiary structure. Although the findings of our study require further wet-lab validation and optimization for therapeutic use in the treatment of shigellosis, the computationally validated siRNA candidates are expected to suppress the expression of the virulence genes, namely: IpgD (siRNA 9) and OspB (siRNA 15 and siRNA 17) and thus act as a prospective tool in the RNA interference (RNAi) pathway. However, the findings of our study require further wet-lab validation and optimization for regular therapeutic use for treatment of shigellosis. |
format | Online Article Text |
id | pubmed-8950558 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89505582022-03-26 A Comprehensive Computational Investigation into the Conserved Virulent Proteins of Shigella species Unveils Potential Small-Interfering RNA Candidates as a New Therapeutic Strategy against Shigellosis Palit, Parag Chowdhury, Farhana Tasnim Baruah, Namrata Sarkar, Bonoshree Mou, Sadia Noor Kamal, Mehnaz Siddiqua, Towfida Jahan Noor, Zannatun Ahmed, Tahmeed Molecules Article Shigella species account for the second-leading cause of deaths due to diarrheal diseases among children of less than 5 years of age. The emergence of multi-drug-resistant Shigella isolates and the lack of availability of Shigella vaccines have led to the pertinence in the efforts made for the development of new therapeutic strategies against shigellosis. Consequently, designing small-interfering RNA (siRNA) candidates against such infectious agents represents a novel approach to propose new therapeutic candidates to curb the rampant rise of anti-microbial resistance in such pathogens. In this study, we analyzed 264 conserved sequences from 15 different conserved virulence genes of Shigella sp., through extensive rational validation using a plethora of first-generation and second-generation computational algorithms for siRNA designing. Fifty-eight siRNA candidates were obtained by using the first-generation algorithms, out of which only 38 siRNA candidates complied with the second-generation rules of siRNA designing. Further computational validation showed that 16 siRNA candidates were found to have a substantial functional efficiency, out of which 11 siRNA candidates were found to be non-immunogenic. Finally, three siRNA candidates exhibited a sterically feasible three-dimensional structure as exhibited by parameters of nucleic acid geometry such as: the probability of wrong sugar puckers, bad backbone confirmations, bad bonds, and bad angles being within the accepted threshold for stable tertiary structure. Although the findings of our study require further wet-lab validation and optimization for therapeutic use in the treatment of shigellosis, the computationally validated siRNA candidates are expected to suppress the expression of the virulence genes, namely: IpgD (siRNA 9) and OspB (siRNA 15 and siRNA 17) and thus act as a prospective tool in the RNA interference (RNAi) pathway. However, the findings of our study require further wet-lab validation and optimization for regular therapeutic use for treatment of shigellosis. MDPI 2022-03-17 /pmc/articles/PMC8950558/ /pubmed/35335300 http://dx.doi.org/10.3390/molecules27061936 Text en © 2022 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 Palit, Parag Chowdhury, Farhana Tasnim Baruah, Namrata Sarkar, Bonoshree Mou, Sadia Noor Kamal, Mehnaz Siddiqua, Towfida Jahan Noor, Zannatun Ahmed, Tahmeed A Comprehensive Computational Investigation into the Conserved Virulent Proteins of Shigella species Unveils Potential Small-Interfering RNA Candidates as a New Therapeutic Strategy against Shigellosis |
title | A Comprehensive Computational Investigation into the Conserved Virulent Proteins of Shigella species Unveils Potential Small-Interfering RNA Candidates as a New Therapeutic Strategy against Shigellosis |
title_full | A Comprehensive Computational Investigation into the Conserved Virulent Proteins of Shigella species Unveils Potential Small-Interfering RNA Candidates as a New Therapeutic Strategy against Shigellosis |
title_fullStr | A Comprehensive Computational Investigation into the Conserved Virulent Proteins of Shigella species Unveils Potential Small-Interfering RNA Candidates as a New Therapeutic Strategy against Shigellosis |
title_full_unstemmed | A Comprehensive Computational Investigation into the Conserved Virulent Proteins of Shigella species Unveils Potential Small-Interfering RNA Candidates as a New Therapeutic Strategy against Shigellosis |
title_short | A Comprehensive Computational Investigation into the Conserved Virulent Proteins of Shigella species Unveils Potential Small-Interfering RNA Candidates as a New Therapeutic Strategy against Shigellosis |
title_sort | comprehensive computational investigation into the conserved virulent proteins of shigella species unveils potential small-interfering rna candidates as a new therapeutic strategy against shigellosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8950558/ https://www.ncbi.nlm.nih.gov/pubmed/35335300 http://dx.doi.org/10.3390/molecules27061936 |
work_keys_str_mv | AT palitparag acomprehensivecomputationalinvestigationintotheconservedvirulentproteinsofshigellaspeciesunveilspotentialsmallinterferingrnacandidatesasanewtherapeuticstrategyagainstshigellosis AT chowdhuryfarhanatasnim acomprehensivecomputationalinvestigationintotheconservedvirulentproteinsofshigellaspeciesunveilspotentialsmallinterferingrnacandidatesasanewtherapeuticstrategyagainstshigellosis AT baruahnamrata acomprehensivecomputationalinvestigationintotheconservedvirulentproteinsofshigellaspeciesunveilspotentialsmallinterferingrnacandidatesasanewtherapeuticstrategyagainstshigellosis AT sarkarbonoshree acomprehensivecomputationalinvestigationintotheconservedvirulentproteinsofshigellaspeciesunveilspotentialsmallinterferingrnacandidatesasanewtherapeuticstrategyagainstshigellosis AT mousadianoor acomprehensivecomputationalinvestigationintotheconservedvirulentproteinsofshigellaspeciesunveilspotentialsmallinterferingrnacandidatesasanewtherapeuticstrategyagainstshigellosis AT kamalmehnaz acomprehensivecomputationalinvestigationintotheconservedvirulentproteinsofshigellaspeciesunveilspotentialsmallinterferingrnacandidatesasanewtherapeuticstrategyagainstshigellosis AT siddiquatowfidajahan acomprehensivecomputationalinvestigationintotheconservedvirulentproteinsofshigellaspeciesunveilspotentialsmallinterferingrnacandidatesasanewtherapeuticstrategyagainstshigellosis AT noorzannatun acomprehensivecomputationalinvestigationintotheconservedvirulentproteinsofshigellaspeciesunveilspotentialsmallinterferingrnacandidatesasanewtherapeuticstrategyagainstshigellosis AT ahmedtahmeed acomprehensivecomputationalinvestigationintotheconservedvirulentproteinsofshigellaspeciesunveilspotentialsmallinterferingrnacandidatesasanewtherapeuticstrategyagainstshigellosis AT palitparag comprehensivecomputationalinvestigationintotheconservedvirulentproteinsofshigellaspeciesunveilspotentialsmallinterferingrnacandidatesasanewtherapeuticstrategyagainstshigellosis AT chowdhuryfarhanatasnim comprehensivecomputationalinvestigationintotheconservedvirulentproteinsofshigellaspeciesunveilspotentialsmallinterferingrnacandidatesasanewtherapeuticstrategyagainstshigellosis AT baruahnamrata comprehensivecomputationalinvestigationintotheconservedvirulentproteinsofshigellaspeciesunveilspotentialsmallinterferingrnacandidatesasanewtherapeuticstrategyagainstshigellosis AT sarkarbonoshree comprehensivecomputationalinvestigationintotheconservedvirulentproteinsofshigellaspeciesunveilspotentialsmallinterferingrnacandidatesasanewtherapeuticstrategyagainstshigellosis AT mousadianoor comprehensivecomputationalinvestigationintotheconservedvirulentproteinsofshigellaspeciesunveilspotentialsmallinterferingrnacandidatesasanewtherapeuticstrategyagainstshigellosis AT kamalmehnaz comprehensivecomputationalinvestigationintotheconservedvirulentproteinsofshigellaspeciesunveilspotentialsmallinterferingrnacandidatesasanewtherapeuticstrategyagainstshigellosis AT siddiquatowfidajahan comprehensivecomputationalinvestigationintotheconservedvirulentproteinsofshigellaspeciesunveilspotentialsmallinterferingrnacandidatesasanewtherapeuticstrategyagainstshigellosis AT noorzannatun comprehensivecomputationalinvestigationintotheconservedvirulentproteinsofshigellaspeciesunveilspotentialsmallinterferingrnacandidatesasanewtherapeuticstrategyagainstshigellosis AT ahmedtahmeed comprehensivecomputationalinvestigationintotheconservedvirulentproteinsofshigellaspeciesunveilspotentialsmallinterferingrnacandidatesasanewtherapeuticstrategyagainstshigellosis |