Antiviral Drugs

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).
• 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

⭐ 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).

⭐ 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).

⭐ 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.