Antiviral Drugs

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Antiviral Drug Targets & MOA - Viral Entry & Exit Experts

  • Viral Entry Inhibitors: Prevent viral access to host cells.
    • Attachment: Maraviroc (HIV; CCR5 antagonist).
    • Fusion: Enfuvirtide (HIV; gp41 inhibitor); Docosanol (HSV). HIV replication cycle and antiviral drug targets
  • Viral Release Inhibitors: Block virion exit from infected cells.
    • Neuraminidase Inhibitors (Influenza A/B): Oseltamivir, Zanamivir.
      • Trap virions by preventing sialic acid cleavage.

    ⭐ Maraviroc requires a tropism test before use to confirm CCR5-tropic HIV.

Anti-Herpes & Anti-Influenza Drugs - Cold Sore & Cough Crushers

Antiviral drug mechanisms of action diagram

⭐ Acyclovir: viral TK for initial phosphorylation; selective. Resistance: TK mutations.

Anti-Herpes Agents:

  • Acyclovir, Valacyclovir:
    • MOA: Guanosine analog; viral TK → DNA pol inhibitor.
    • Uses: HSV, VZV.
    • AE: Crystalline nephropathy.
  • Ganciclovir, Valganciclovir:
    • MOA: Viral UL97 (CMV) activation.
    • Uses: CMV retinitis.
    • AE: Myelosuppression. 📌 "Gan-cyc-LOW-vir".
  • Foscarnet:
    • MOA: Direct DNA pol inhibitor; no activation.
    • Uses: Resistant HSV, VZV, CMV.
    • AE: Nephrotoxic, electrolytes ↓.
  • Cidofovir:
    • MOA: Nucleotide analog; DNA pol inhibitor.
    • Uses: Resistant CMV.
    • AE: Nephrotoxic (w/ Probenecid).

Anti-Influenza Agents:

  • Neuraminidase Inhibitors (NAIs): Oseltamivir (PO), Zanamivir (inhaled), Peramivir (IV).
    • MOA: Prevents virion release.
    • Uses: Flu A/B (start <48h).
    • AE: Oseltamivir: GI; Zanamivir: bronchospasm.
  • Baloxavir marboxil:
    • MOA: Endonuclease inhibitor (mRNA block).
    • Uses: Flu A/B (single dose).

Anti-Hepatitis (HBV & HCV) Drugs - Liver's Viral Vanquishers

  • Hepatitis B (HBV) - Chronic Management:
    • NRTIs (Nucleos(t)ide Analogs):
      • Preferred: Tenofovir (TDF/TAF), Entecavir.
      • MOA: Inhibit HBV DNA polymerase.
      • Tenofovir: TDF (nephrotoxic, ↓bone density); TAF (safer).
      • Entecavir: Potent, high resistance barrier.
    • Pegylated Interferon alfa-2a (Peg-IFNα):
      • MOA: Immunomodulator. Finite (48 wks) therapy.
      • S/E: Flu-like, depression, cytopenias.
  • Hepatitis C (HCV) - Direct-Acting Antivirals (DAAs):
    • Classes (📌 HCV DAAs: -previr, -asvir, -buvir):
      • NS3/4A Protease-I (-previr): e.g., Glecaprevir.
      • NS5A-I (-asvir): e.g., Velpatasvir.
      • NS5B Polymerase-I (-buvir): e.g., Sofosbuvir.
    • Pangenotypic regimens (e.g., Sofosbuvir/Velpatasvir, Glecaprevir/Pibrentasvir) offer >95% SVR (cure).
    • Well-tolerated; short duration (8-12 wks).

HCV life cycle and antiviral targets

⭐ Sofosbuvir (HCV NS5B inhibitor) is pangenotypic; ⚠️ contraindicated with amiodarone due to risk of severe symptomatic bradycardia.

Antiretroviral Drugs (ART for HIV) - HIV's Resistance Wreckers

  • Goal: Suppress HIV, restore immunity, prevent transmission.

  • Regimen: Typically 2 NRTIs + 1 INSTI.

  • NRTIs (Nucleoside/Nucleotide Reverse Transcriptase Inhibitors): Zidovudine (AZT), Lamivudine (3TC), Abacavir (ABC), Tenofovir (TDF/TAF), Emtricitabine (FTC).

    • MoA: Chain termination by inhibiting reverse transcriptase.
    • 📌 SE: Lactic acidosis. AZT: Anemia. TDF: Nephrotoxic, bone loss. ABC: Hypersensitivity (test HLA-B*5701).
  • NNRTIs (Non-Nucleoside Reverse Transcriptase Inhibitors): Efavirenz (EFV), Nevirapine (NVP), Rilpivirine (RPV).

    • MoA: Allosteric inhibition of reverse transcriptase.
    • SE: Rash (SJS/TEN), hepatotoxicity. EFV: CNS effects.
  • PIs (Protease Inhibitors): Atazanavir (ATV), Darunavir (DRV), Lopinavir/Ritonavir (LPV/r).

    • MoA: Inhibit HIV protease, preventing viral maturation.
    • SE: Metabolic syndrome (hyperlipidemia, hyperglycemia), lipodystrophy. Ritonavir boosts (CYP3A4 inhibitor).
  • INSTIs (Integrase Strand Transfer Inhibitors): Raltegravir (RAL), Dolutegravir (DTG), Bictegravir (BIC).

    • MoA: Block integrase, preventing viral DNA integration.
    • SE: Generally well-tolerated. DTG: ↑creatinine (benign), rare insomnia/neural tube defect risk.
  • Entry Inhibitors:

    • Fusion Inhibitor: Enfuvirtide (binds gp41).
    • CCR5 Antagonist: Maraviroc (blocks CCR5; tropism test needed).

HIV life cycle and antiretroviral drug targets

Preferred initial ART for most treatment-naive adults: 2 NRTIs (e.g., Tenofovir alafenamide/Emtricitabine or Abacavir/Lamivudine) + 1 INSTI (e.g., Dolutegravir or Bictegravir).

High‑Yield Points - ⚡ Biggest Takeaways

  • Acyclovir: Guanosine analog, activated by viral thymidine kinase. DOC for HSV & VZV. Risk of nephrotoxicity.
  • Ganciclovir: Preferred for CMV retinitis. Major side effect: myelosuppression.
  • Foscarnet: Treats resistant CMV/HSV. Causes nephrotoxicity, electrolyte imbalance.
  • Oseltamivir/Zanamivir: Neuraminidase inhibitors for Influenza A & B treatment and prophylaxis.
  • Ribavirin: For chronic Hepatitis C (with DAAs), RSV. Teratogenic, hemolytic anemia.
  • Tenofovir/Entecavir: Key NRTIs for Hepatitis B. Sofosbuvir (DAA) for pangenotypic Hepatitis C.
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Practice Questions: Antiviral Drugs

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Flashcards: Antiviral Drugs

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The endonuclease inhibitor for the treatment of acute uncomplicated influenza in adults is _____.

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The endonuclease inhibitor for the treatment of acute uncomplicated influenza in adults is _____.

baloxavir marboxil

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