A Comprehensive Computational Investigation into the Conserved Virulent Proteins of <i>Shigella</i> species Unveils Potential Small-Interfering RNA Candidates as a New Therapeutic Strategy against Shigellosis
<i>Shigella</i> 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 <i>Shigella</i> isolates and the lack of availability of <i>Shigella</i> vaccines hav...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-03-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/27/6/1936 |
| _version_ | 1797444285108322304 |
|---|---|
| author | Parag Palit Farhana Tasnim Chowdhury Namrata Baruah Bonoshree Sarkar Sadia Noor Mou Mehnaz Kamal Towfida Jahan Siddiqua Zannatun Noor Tahmeed Ahmed |
| author_facet | Parag Palit Farhana Tasnim Chowdhury Namrata Baruah Bonoshree Sarkar Sadia Noor Mou Mehnaz Kamal Towfida Jahan Siddiqua Zannatun Noor Tahmeed Ahmed |
| author_sort | Parag Palit |
| collection | DOAJ |
| description | <i>Shigella</i> 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 <i>Shigella</i> isolates and the lack of availability of <i>Shigella</i> 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 <i>Shigella</i> 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. |
| first_indexed | 2024-03-09T13:09:24Z |
| format | Article |
| id | doaj.art-2b9aa7e352894630bd74732b21a2e760 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T13:09:24Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-2b9aa7e352894630bd74732b21a2e7602023-11-30T21:43:31ZengMDPI AGMolecules1420-30492022-03-01276193610.3390/molecules27061936A Comprehensive Computational Investigation into the Conserved Virulent Proteins of <i>Shigella</i> species Unveils Potential Small-Interfering RNA Candidates as a New Therapeutic Strategy against ShigellosisParag Palit0Farhana Tasnim Chowdhury1Namrata Baruah2Bonoshree Sarkar3Sadia Noor Mou4Mehnaz Kamal5Towfida Jahan Siddiqua6Zannatun Noor7Tahmeed Ahmed8International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka 1212, BangladeshDepartment of Biochemistry and Molecular Biology, University of Dhaka, Dhaka 1000, BangladeshDepartment of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur 208016, Uttar Pradesh, IndiaDepartment of Biochemistry and Molecular Biology, University of Dhaka, Dhaka 1000, BangladeshDepartment of Biochemistry and Molecular Biology, University of Dhaka, Dhaka 1000, BangladeshInternational Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka 1212, BangladeshInternational Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka 1212, BangladeshInternational Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka 1212, BangladeshInternational Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka 1212, Bangladesh<i>Shigella</i> 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 <i>Shigella</i> isolates and the lack of availability of <i>Shigella</i> 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 <i>Shigella</i> 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.https://www.mdpi.com/1420-3049/27/6/1936<i>Shigella</i>small-interfering RNAcomputational algorithmsRNAi pathwayshigellosis |
| spellingShingle | Parag Palit Farhana Tasnim Chowdhury Namrata Baruah Bonoshree Sarkar Sadia Noor Mou Mehnaz Kamal Towfida Jahan Siddiqua Zannatun Noor Tahmeed Ahmed A Comprehensive Computational Investigation into the Conserved Virulent Proteins of <i>Shigella</i> species Unveils Potential Small-Interfering RNA Candidates as a New Therapeutic Strategy against Shigellosis Molecules <i>Shigella</i> small-interfering RNA computational algorithms RNAi pathway shigellosis |
| title | A Comprehensive Computational Investigation into the Conserved Virulent Proteins of <i>Shigella</i> 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 <i>Shigella</i> 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 <i>Shigella</i> 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 <i>Shigella</i> 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 <i>Shigella</i> 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 i shigella i species unveils potential small interfering rna candidates as a new therapeutic strategy against shigellosis |
| topic | <i>Shigella</i> small-interfering RNA computational algorithms RNAi pathway shigellosis |
| url | https://www.mdpi.com/1420-3049/27/6/1936 |
| work_keys_str_mv | AT paragpalit acomprehensivecomputationalinvestigationintotheconservedvirulentproteinsofishigellaispeciesunveilspotentialsmallinterferingrnacandidatesasanewtherapeuticstrategyagainstshigellosis AT farhanatasnimchowdhury acomprehensivecomputationalinvestigationintotheconservedvirulentproteinsofishigellaispeciesunveilspotentialsmallinterferingrnacandidatesasanewtherapeuticstrategyagainstshigellosis AT namratabaruah acomprehensivecomputationalinvestigationintotheconservedvirulentproteinsofishigellaispeciesunveilspotentialsmallinterferingrnacandidatesasanewtherapeuticstrategyagainstshigellosis AT bonoshreesarkar acomprehensivecomputationalinvestigationintotheconservedvirulentproteinsofishigellaispeciesunveilspotentialsmallinterferingrnacandidatesasanewtherapeuticstrategyagainstshigellosis AT sadianoormou acomprehensivecomputationalinvestigationintotheconservedvirulentproteinsofishigellaispeciesunveilspotentialsmallinterferingrnacandidatesasanewtherapeuticstrategyagainstshigellosis AT mehnazkamal acomprehensivecomputationalinvestigationintotheconservedvirulentproteinsofishigellaispeciesunveilspotentialsmallinterferingrnacandidatesasanewtherapeuticstrategyagainstshigellosis AT towfidajahansiddiqua acomprehensivecomputationalinvestigationintotheconservedvirulentproteinsofishigellaispeciesunveilspotentialsmallinterferingrnacandidatesasanewtherapeuticstrategyagainstshigellosis AT zannatunnoor acomprehensivecomputationalinvestigationintotheconservedvirulentproteinsofishigellaispeciesunveilspotentialsmallinterferingrnacandidatesasanewtherapeuticstrategyagainstshigellosis AT tahmeedahmed acomprehensivecomputationalinvestigationintotheconservedvirulentproteinsofishigellaispeciesunveilspotentialsmallinterferingrnacandidatesasanewtherapeuticstrategyagainstshigellosis AT paragpalit comprehensivecomputationalinvestigationintotheconservedvirulentproteinsofishigellaispeciesunveilspotentialsmallinterferingrnacandidatesasanewtherapeuticstrategyagainstshigellosis AT farhanatasnimchowdhury comprehensivecomputationalinvestigationintotheconservedvirulentproteinsofishigellaispeciesunveilspotentialsmallinterferingrnacandidatesasanewtherapeuticstrategyagainstshigellosis AT namratabaruah comprehensivecomputationalinvestigationintotheconservedvirulentproteinsofishigellaispeciesunveilspotentialsmallinterferingrnacandidatesasanewtherapeuticstrategyagainstshigellosis AT bonoshreesarkar comprehensivecomputationalinvestigationintotheconservedvirulentproteinsofishigellaispeciesunveilspotentialsmallinterferingrnacandidatesasanewtherapeuticstrategyagainstshigellosis AT sadianoormou comprehensivecomputationalinvestigationintotheconservedvirulentproteinsofishigellaispeciesunveilspotentialsmallinterferingrnacandidatesasanewtherapeuticstrategyagainstshigellosis AT mehnazkamal comprehensivecomputationalinvestigationintotheconservedvirulentproteinsofishigellaispeciesunveilspotentialsmallinterferingrnacandidatesasanewtherapeuticstrategyagainstshigellosis AT towfidajahansiddiqua comprehensivecomputationalinvestigationintotheconservedvirulentproteinsofishigellaispeciesunveilspotentialsmallinterferingrnacandidatesasanewtherapeuticstrategyagainstshigellosis AT zannatunnoor comprehensivecomputationalinvestigationintotheconservedvirulentproteinsofishigellaispeciesunveilspotentialsmallinterferingrnacandidatesasanewtherapeuticstrategyagainstshigellosis AT tahmeedahmed comprehensivecomputationalinvestigationintotheconservedvirulentproteinsofishigellaispeciesunveilspotentialsmallinterferingrnacandidatesasanewtherapeuticstrategyagainstshigellosis |