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Porcine reproductive and respiratory syndrome virus (PRRSV) replication is the central process of viral genome duplication and gene expression within host porcine alveolar macrophages. This process is executed by the replication-transcription complex (RTC), a sophisticated assembly of non-structural proteins (Nsps) derived from the autoproteolytic cleavage of the viral polyproteins pp1a and pp1ab (PMID: 28250119). Key enzymatic components include the RNA-dependent RNA polymerase (Nsp9), which catalyzes RNA synthesis, and the 3C-like serine protease (Nsp4), which is essential for polyprotein processing (PMID: 31142501, 25855250). As a therapeutic target, the PRRSV replication machinery is highly significant for the development of antiviral drugs to mitigate the severe economic impact of PRRS on the swine industry (Wikipedia). Inhibitors such as nucleoside analogs and protease inhibitors aim to disrupt these viral functions to reduce viral load and clinical symptoms (PMID: 33458185). However, the high mutation rate of the PRRSV genome frequently leads to the emergence of drug-resistant strains, complicating long-term therapeutic strategies (PMID: 30654045).
Inhibition of the RNA-dependent RNA polymerase (Nsp9), inhibition of viral proteases (Nsp4/3CLpro), and disruption of the assembly of the replication-transcription complex.
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