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

Abstract

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.