Exploring novel therapeutic strategies against vivax malaria through an integrated computational investigation to inhibit the merozoite surface protein−1 of Plasmodium vivax

Islam, Ovinu Kibria; Palit, Partha; Shawon, Jakaria; Hasan, Md. Kamrul; Mahmud, Araf; Mahfuz, Mustafa; Ahmed, Tahmeed; Mondal, Dinesh

doi:10.1016/j.imu.2020.100471

Cited by 2 publications

(4 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Subsequently, the MOLProbity web server was used to validate the individual tertiary structures of the non-immunogenic siRNA candidates, and the 3D structures were then filtered for clash score/the number of serious steric overlaps (>0.4 Å) per 1000 atoms [ 65 ]. In the MOLProbity web server, the threshold for the different aspects of nucleic acid geometry, including the probability of wrong sugar puckers, bad backbone confirmations, and bad angles was considered to be 5%, as recommended by the guidelines of the web server and by previously published research that had used this web server [ 41 , 65 , 79 ]. Moreover, the score for all atom contacts was considered to be acceptable if the clashscore was greater than or equal to the 33rd percentile, as recommended by previous literature [ 41 , 79 ].…”

Section: Resultsmentioning

confidence: 99%

“…In the MOLProbity web server, the threshold for the different aspects of nucleic acid geometry, including the probability of wrong sugar puckers, bad backbone confirmations, and bad angles was considered to be 5%, as recommended by the guidelines of the web server and by previously published research that had used this web server [ 41 , 65 , 79 ]. Moreover, the score for all atom contacts was considered to be acceptable if the clashscore was greater than or equal to the 33rd percentile, as recommended by previous literature [ 41 , 79 ]. Validation scores for the predicted 3D structures of the siRNA candidates are shown in Table 4 .…”

Section: Resultsmentioning

confidence: 99%

“…Small-interfering RNA (siRNA) represent a class of exogenous double-stranded non-coding RNA that bind to specific sequences of the related messenger RNA (mRNA) and promote the process of degradation of the mRNA, eventually halting the process of transcription [ 40 ]. Concurrent works involving the use of a plethora of computational tools and algorithms have designed potential therapeutic siRNA candidates against a number of infectious organisms, including P.vivax [ 41 ] and L.donovani [ 42 ]; the COVID-19 pandemic causing SARS-CoV-2 [ 43 ]; and against a number of bacterial pathogens, such as: M. tuberculosis [ 44 ], Salmonella [ 45 ], and Listeria [ 46 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2022

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…Small-interfering RNA (siRNA) represent a class of exogenous double-stranded non-coding RNA that binds with specific sequences of a messenger RNA (mRNA) and promotes the process of degradation of the mRNA, eventually halting the process of transcription (40). Concurrent works involving the use of a plethora of computational tools and algorithms have been design potential therapeutic siRNA candidates against a number of infectious organisms, including P.vivax (41) and L.donovani (42), the COVID-19 pandemic causing SARS-CoV-2 (43) and against a number of bacterial pathogens, such as: M. tuberculosis (44), Salmonella (45) and Listeria (46).…”

Section: Introductionmentioning

confidence: 99%

A comprehensive computational investigation into the conserved virulent proteins ofShigellasp unveils potential siRNA candidates as a new therapeutic strategy against shigellosis

Palit

Chowdhury²,

Sarkar³

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Shigella sp account for the second-leading cause of deaths due to diarrheal diseases among children of less than 5 years of age. Emergence of multi-drug resistant Shigella isolates and the lack of availability of Shigella vaccines have made the efforts in the development of new therapeutic strategies against shigellosis very pertinent. In our study we have analyzed a total of 241 conserved sequences from a 15 different conserved virulence genes of Shigella sp and through extensive rational validation using a plethora of computational algorithms; we primarily obtained fifty eight small-interfering RNA (siRNA) candidates. Further extensive computational validation showed only three siRNA candidates that were found to exhibit substantial functional efficacy, be non-immunogenic and have a thermodynamically stable and sterically feasible and thereby acceptable tertiary structure. These siRNA candidates are intended 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 in the treatment of shigellosis. Keywords: Shigella, siRNA, computational algorithms.

show abstract

Exploring novel therapeutic strategies against vivax malaria through an integrated computational investigation to inhibit the merozoite surface protein−1 of Plasmodium vivax

Cited by 2 publications

References 74 publications

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

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

A comprehensive computational investigation into the conserved virulent proteins ofShigellasp unveils potential siRNA candidates as a new therapeutic strategy against shigellosis

Contact Info

Product

Resources

About