Clinical meaning
Understanding viral replication cycles is essential for NP antiviral prescribing, as each antiviral drug targets a specific step in the viral life cycle. The general viral replication cycle consists of: (1) Attachment and entry — virus binds to host cell surface receptors (HIV gp120 binds CD4; influenza hemagglutinin binds sialic acid; SARS-CoV-2 spike protein binds ACE2); entry occurs via receptor-mediated endocytosis or membrane fusion; drug target: entry inhibitors (maraviroc blocks CCR5 co-receptor for HIV; oseltamivir is a neuraminidase inhibitor preventing influenza release but must be given within 48 hours of symptom onset). (2) Uncoating and genome release — viral capsid disassembles, releasing nucleic acid into the cytoplasm; drug target: amantadine blocks M2 ion channel of influenza A (high resistance, no longer recommended). (3) Genome replication — DNA viruses typically replicate in the nucleus using host or viral DNA polymerase; RNA viruses use RNA-dependent RNA polymerase (RdRp); retroviruses (HIV) use reverse transcriptase to convert RNA to DNA; drug targets: nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs: tenofovir, emtricitabine — chain terminators for HIV), non-nucleoside RTIs (NNRTIs: efavirenz), viral polymerase inhibitors (acyclovir — requires phosphorylation by viral thymidine kinase, selectively targeting herpes-infected cells; sofosbuvir — NS5B polymerase inhibitor for HCV; remdesivir — RdRp inhibitor for SARS-CoV-2). (4) Assembly and maturation — new viral particles are assembled; protease enzymes cleave polyproteins into functional units; drug targets: HIV protease inhibitors (ritonavir, darunavir), HCV NS3/4A protease inhibitors (glecaprevir). (5) Release — new virions exit the cell; budding viruses (enveloped) exit through the plasma membrane; lytic viruses (non-enveloped) exit through cell lysis; drug target: neuraminidase inhibitors (oseltamivir, zanamivir) prevent influenza virion release by blocking neuraminidase cleavage of sialic acid.