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Mouse hepatitis virus strain A59 (MHV-A59) replication is the multi-stage biological process by which this murine betacoronavirus reproduces within a host cell (PubMed: 21353105). The cycle begins with the translation of the viral positive-sense RNA genome into two large polyproteins, which are subsequently cleaved by viral proteases, such as the 3C-like protease (nsp5), into functional non-structural proteins (UniProt: P0C6U8). These proteins assemble into the replicase-transcriptase complex, where the RNA-dependent RNA polymerase (nsp12) catalyzes the synthesis of new genomic and subgenomic RNAs (PubMed: 16439519). Because replication describes a multi-step pathway rather than a single molecular entity, it is typically categorized as a phenotypic endpoint in drug discovery rather than a specific therapeutic target. Antiviral agents targeting this process, such as remdesivir or protease inhibitors like GC376, work by disrupting specific enzymatic components of the replication machinery to halt viral spread (PubMed: 32358203). MHV-A59 is frequently used as a surrogate model in research to understand the replication mechanisms and pathogenesis of human coronaviruses like SARS-CoV-2 (PubMed: 32221306).
Inhibition of viral RNA-dependent RNA polymerase and viral proteases
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