Pharmacology of Antiviral Drugs

Introduction Antiviral pharmacology has advanced from the single-agent era of idoxuridine to a modern arsenal including polymerase terminators, protease blockers, monoclonal antibodies, and host-directed entry inhibitors. Because viruses are obligate intracellular parasites, therapy emphasises selective toxicity—halting viral replication without irreparable host harm. This page delivers a section-wise, visually enhanced overview of the major antiviral classes, mechanisms, PK profiles, indications, resistance, and safety. 1. General Principles of Antiviral Therapy 2. Anti-Herpesvirus Agents 2.1 Nucleoside Analogues DrugActivationMechanismPK HighlightsMajor ToxicitiesAcyclovirHSV TK ➜ host kinasesDNA-pol chain terminationIV/PO; CSF ≈50 %Crystalline nephropathy, neurotoxicity at high doseValacyclovirPro-acyclovir (↑ F 55 %)SamePO onlySimilar, less frequentGanciclovirUL97 kinaseDNA-pol inhibition + terminationIV; low PO FMyelosuppression, CNS effectsValganciclovirPro-ganciclovirSamePO F 60 %As aboveCidofovirHost kinases onlyDNA-pol inhibitorIV; long IC t½Renal toxicity (⇣ with probenecid + saline)FoscarnetNone (pyrophosphate)Blocks DNA-pol/RTIV; CSF 70 %Nephrotoxicity, ↓ Ca²⁺/Mg²⁺, seizures Resistance TK-negative HSV mutants resist acyclovir; CMV UL97/DNA-pol mutants limit ganciclovir and cidofovir; foscarnet holds until polymerase mutations arise. 3. Anti-Influenza Drugs 3.1 M2 Ion-Channel Inhibitors Amantadine & rimantadine block influenza A uncoating—now obsolete due to universal resistance. 3.2 Neuraminidase Inhibitors DrugSpectrumRouteClinical NotesOseltamivirA & BPON/V; rare neuropsychiatric eventsZanamivirA & BInhaledBronchospasm—avoid asthma/COPDPeramivirA & BIV (single dose)Diarrhoea 3.3 Cap-Endonuclease Inhibitor Baloxavir marboxil (single-dose PO) halts PA-mediated “cap-snatching”. I38T mutations reduce susceptibility. 4. Anti-RSV & Emerging Respiratory Viruses 5. Anti-Hepatitis Agents 5.1 HBV 5.2 HCV – Direct-Acting Antivirals ClassSuffixPrototypeKey PointNS3/4A PI-previrGlecaprevirCI in Child-Pugh B/CNS5A Inhibitor-asvirVelpatasvirWell-toleratedNS5B Nuc Pol Inhib.-buvirSofosbuvirBradycardia w/ amiodarone 5.3 HDV Bulevertide (SC) blocks NTCP entry; first licensed HDV drug. 6. Antiretroviral Therapy (HIV-1/2) Standard regimen: 2 NRTIs + 1 high-barrier anchor (INSTI > boosted PI > NNRTI). 6.1 NRTIs 6.2 NNRTIs & 6.3 Protease Inhibitors Efavirenz (CNS dreams); rilpivirine (needs acid). Darunavir (rash, high barrier); atazanavir (hyperbilirubinaemia), all boosted by ritonavir/cobicistat (CYP3A4 DDIs). 6.4 INSTIs & 6.5 Entry/Fusion Dolutegravir & bictegravir are first-line; long-acting IM cabotegravir/rilpivirine monthly. Maraviroc (CCR5), enfuvirtide (gp41), ibalizumab (post-attachment). 7. Anti-Poxvirus Drugs 8. Pharmacokinetic Considerations 9. Resistance Mechanisms 10. Adverse-Effect Themes & Monitoring 11. Special Populations 12. Immunomodulatory & Passive Agents 13. Emerging & Future Therapies 14. Conclusion The antiviral pharmacopeia epitomises the synergy of molecular virology and medicinal chemistry, converting lethal infections into manageable or curable diseases. Ongoing innovation remains essential to outpace resistance, PK variability, and emerging pathogens. Selected Textbook References