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.