Abstract
<title>Abstract</title> <p>Despite the availability of an effective vaccine, measles virus (MV) remains a major global health concern because no approved antiviral therapeutics currently exist. RNA interference (RNAi) is a promising antiviral strategy, but studies targeting the conserved MV hemagglutinin (H) gene are limited. In this study, an integrated computational pipeline was used to identify and evaluate novel siRNA candidates targeting the MV H gene. At first, 96 MV strains were used to perform multiple sequence alignment (MSA) to generate a consensus sequence, and the phylogenetic tree demonstrated limited genetic divergence among the strains. 11 siRNA candidates were then designed and screened for off-target effects. Subsequently, they were subjected to thermodynamic analysis, secondary and tertiary structure prediction, hybridization energy evaluation, and molecular docking against human Argonaute-2 (hAgo2). The docking results showed that S3, S4, and S7 displayed docking scores of -367.22, − 349.03, and − 383.07 kcal/mol with the most favorable binding orientation within the catalytic PIWI domain of hAgo2. The three selected candidates maintained stable structural behavior throughout 100 ns molecular dynamics (MD) simulations. These computational analyses indicate that the S3, S4, and S7 may serve as promising siRNA candidates against the MV H gene, which require further in vitro gene silencing assays and in vivo validation.</p>