Designing of potential siRNA molecules for African norovirus gene silencing: A computational approach

Abstract

Introducing siRNAs into cells could degrade specific messenger RNA (mRNA) molecules, reducing the expression of the corresponding protein encoded by those mRNA molecules. Norovirus is the leading cause of both epidemic and pandemic acute gastroenteritis, which is inflammation of the stomach and intestine worldwide, and, as of present, no efficient vaccine is available to combat this norovirus disease. Since siRNA, therapeutics have gained significant attention for their potential to target and silence disease-causing genes. Our study utilizes different computational tools to design siRNA agents against the polyprotein of norovirus without causing off-target effects. According to the results of GC (guanine-cytosine) content, fold-free energy, binding energy, melting temperature, efficacy predictions, and molecular docking against human argonaute 2 protein (AGO2), two siRNA molecules are expected to exert the most effective action. The effectiveness and efficiency of siRNAs against norovirus need to be further examined in vivo before their use as alternative and practical molecular therapeutic agents. • Potential siRNA molecules were identified to target and silence the African Norovirus infection gene. • Molecular docking and dynamics simulations confirmed the binding efficiency and interaction stability of the most promising siRNA with human AGO2 protein. • The findings may facilitate the creation of novel Norovirus therapies, but necessitate additional in vitro and in vivo validation.