Bioinformatics prediction of siRNAs as potential antiviral agents against dengue viruses

Abstract

Dengue virus (DENV 1-4) represents the major emerging arthropod-borne viral infection in the world. Currently, there is neither an available vaccine nor a specific treatment. Hence, there is a need of antiviral drugs for these viral infections; we describe the prediction of short interfering RNA (siRNA) as potential therapeutic agents against the four DENV serotypes. Our strategy was to carry out a series of multiple alignments using ClustalX program to find conserved sequences among the four DENV serotype genomes to obtain a consensus sequence for siRNAs design. A highly conserved sequence among the four DENV serotypes, located in the encoding sequence for NS4B and NS5 proteins was found. A total of 2,893 complete DENV genomes were downloaded from the NCBI, and after a depuration procedure to identify identical sequences, 220 complete DENV genomes were left. They were edited to select the NS4B and NS5 sequences, which were aligned to obtain a consensus sequence. Three different servers were used for siRNA design, and the resulting siRNAs were aligned to identify the most prevalent sequences. Three siRNAs were chosen, one targeted the genome region that codifies for NS4B protein and the other two; the region for NS5 protein. Predicted secondary structure for DENV genomes was used to demonstrate that the siRNAs were able to target the viral genome forming double stranded structures, necessary to activate the RNA silencing machinery.

Potential siRNA Molecules for Nucleoprotein and M2/L Overlapping Region of Respiratory Syncytial Virus: In Silico Design

“…Since viruses are known to be genetically diverse ( 34 ), some researchers have focused more on conserved target sites to design siRNAs. Rosales et al have used this approach to design siRNAs against NS4B and NS5 of the Dengue virus ( 35 ). Likewise Raza et al predicted siRNA against the conserved region of HA and NA genes of the Influenza A virus ( 36 ).…”

siRNAs encapsulated in recombinant capsid protein derived from Dengue serotype 2 virus inhibits the four serotypes of the virus and proliferation of cancer cells

“…The DENV specific siRNAs used in the study targeted conserved sites in the DENV genome reported in previous studies (Kyle et al, 2007;Villegas-Rosales et al, 2012;Swamy et al, 2006), but the target sequences of these siRNAs were not exactly the same as those reported in the above studies (Supplementary Table 1). To avoid interferon mediated non-specific gene silencing, the length of each strand of all siRNA duplexes was 21-27 nucleotides.…”

Antivirals Against Coronaviruses: Candidate Drugs for SARS-CoV-2 Treatment?

“…Also, the exploitation of in silico studies for drug screening to seek specific targets, as well as for a better comprehension of their interactions with viral biomolecules, has been shown as a promising tool for expediting drug development. By narrowing down the number of drug candidates, in silico studies have the potential to avoid the laborious and generally costly synthesis of many of these compounds (Lengauer and Sing, 2006;Villegas-Rosales et al, 2012). Nevertheless, several predicted compounds in the literature have only been screened by in silico and/or interaction assays (Chen et al, 2005;Kaeppler et al, 2005;Lee et al, 2005;Kim et al, 2012;Arya et al, 2020;Balasubramaniam and Reis, 2020), which ultimately hinders the proper assessment of the antiviral activities of the compounds.…”