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Coronavirus viral RNA is the positive-sense single-stranded RNA (+ssRNA) genome that characterizes viruses in the Coronaviridae family, including SARS-CoV-2, SARS-CoV, and MERS-CoV (V'kovski et al., 2021). It functions as both the genetic blueprint for the virus and a direct template for the translation of viral proteins by the host cell's machinery (Fehr & Perlman, 2015). The genome is exceptionally large for an RNA virus, typically ranging from 26 to 32 kilobases, and contains a 5' cap and a 3' polyadenylated tail, mimicking host mRNA to facilitate immediate translation upon entry (V'kovski et al., 2021). During the viral life cycle, the RNA is replicated via a negative-sense intermediate by the viral RNA-dependent RNA polymerase (RdRp) complex (Snijder et al., 2016). This replication process is a primary target for antiviral therapy; nucleoside analogs like molnupiravir are incorporated into the nascent RNA strand, causing widespread mutations that lead to error catastrophe and viral extinction (Jayk Bernal et al., 2022; Kabinger et al., 2021). Additionally, experimental approaches such as antisense oligonucleotides and siRNA are designed to specifically bind and catalyze the degradation of the viral RNA, preventing the production of viral components (Zhu et al., 2022).
Nucleoside analogs act as alternative substrates for the viral RNA-dependent RNA polymerase (RdRp). Once incorporated into the nascent viral RNA strand, they either cause premature chain termination (e.g., remdesivir) or induce an unsustainable frequency of mutations during subsequent replication cycles, a process known as lethal mutagenesis or error catastrophe (e.g., molnupiravir). Experimental therapies like siRNA and antisense oligonucleotides (ASOs) target specific sequences of the viral RNA to trigger enzymatic degradation or physically block translation and replication.
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