SARS-CoV-2 Replication Revisited: Molecular Insights and Current and Emerging Antiviral Strategies

SARS-CoV-2 replication remains a critical and main target for therapeutic interventions. The current review synthesizes existing knowledge to provide an in-depth analysis of molecular insights and both current and emerging therapy methods, moving past reviews centered on antivirals and general replication processes. We examined antiviral tactics aimed at these replication pathways, including direct-acting nucleoside analogs (remdesivir, molnupiravir), protease inhibitors (nirmatrelvir), and host-directed agents influencing viral entry and RNA synthesis. Emphasizing therapeutic constraints and evolutionary escape, this study also investigates synergistic drug combinations and resistance mechanisms. Discussed for their capacity to efficiently handle next coronavirus dangers are emerging methods—from CRISPR-based gene-silencing, nanoparticle-delivered siRNAs, and AI-driven drug discovery. Highlighted as new antiviral targets are host-pathogen interactions including adaptation via the TRiC complex and phosphatase pathways. This paper offers a road map for improving therapeutic tactics against SARS-CoV-2 and related developing viruses with molecular virology, pharmacology, and computational biology.