Unveiling the translational and therapeutic potential of small interfering RNA molecules in combating SARS-CoV-2: A review.

The global COVID-19 pandemic, caused by SARS-CoV-2, has led to significant mortality, with over 6.5 million deaths worldwide. While vaccines have played a crucial role in reducing disease severity, the emergence of viral variants continues to undermine vaccine efficacy, highlighting the need for alternative antiviral strategies. This review explores the potential of RNA interference (RNAi), particularly small interfering RNAs (siRNAs), as a targeted therapeutic approach against SARS-CoV-2. siRNAs can silence specific viral genes with high precision, effectively inhibiting viral replication. We discuss the design and mechanism of siRNAs, their primary molecular targets such as the spike (S), membrane (M), and RNA-dependent RNA polymerase (RdRp) genes and summarize past and current research findings. Special emphasis is placed on delivery systems, especially lung-targeted strategies essential for respiratory infections. We also evaluate how siRNA therapeutics can overcome challenges posed by viral mutations and treatment resistance. The novelty of this work lies in its focused comparison of siRNAs with other non-coding RNAs and its integration of computational tools for siRNA design. This review presents a strategic overview of siRNA development and highlights its translational potential for the current pandemic and future coronavirus outbreaks.