LC13c_ANTIVIRAL AGENTS

I. VIRAL REPLICATION STEPS

  • Viruses are obligate intracellular pathogens that require a host cell to reproduce. The replication cycle generally consists of six stages:

    • Attachment: Viral surface proteins bind to specific receptors on the host cell, determining the virus’s host range (tropism).

    • Penetration: The virus either fuses with the cell membrane or is absorbed by receptor-mediated endocytosis.

    • Uncoating: The viral capsid is dismantled, releasing the genome.

    • Replication: The viral genome undergoes transcription and translation; processes vary for DNA and RNA viruses.

    • Assembly: Newly synthesized viral proteins and genomes are packaged into new virions.

    • Virion Release: New viruses exit the host cell by lysis (cell death) or budding, especially for enveloped viruses.

  • After release, leftover viral proteins can trigger immune responses; surface proteins are recognized by antibodies, while internal proteins are presented via MHC class I molecules to T cells.

  • Antiviral drugs interfering with the replication steps include:

    • Attachment and Entry Blockers: Enfuvirtide (HIV), Docosanol (HSV), Maraviroc (HIV), and Palivizumab (RSV).

    • Penetration Blockers: Interferon-alpha (HBV, HCV).

    • Uncoating Blockers: Amantadine and Rimantadine (influenza).

    • Nucleic Acid Synthesis Blockers: NRTIs, NNRTIs (HIV), and Nucleoside/Nucleotide analogs (HSV, HBV).

    • Integration Blockers: INSTIs (HIV).

    • Protein Synthesis Blockers: PIs (HIV, HCV).

    • Release Blockers: Neuraminidase inhibitors (influenza).

II. ANTI-HERPES DRUGS

A. Agents to Treat Herpes Simplex Virus (HSV) & Varicella-Zoster Virus (VZV) Infections

  • Drugs include: Aciclovir, Valacyclovir, Famciclovir

  • Effects on HSV Treatment:

    • Shortens symptom duration by 2 days.

    • Reduces healing time of lesions by 4 days.

    • Decreases the duration of viral shedding by 7 days during first episodes of genital herpes.

    • Affects recurrence duration by 1-2 days in recurrent genital herpes.

A.1. Herpes Simplex Virus (HSV)

  • Commonly causes painful blisters or ulcers.

  • Transmission occurs via skin-to-skin contact.

  • Treatable but not curable with two main types:

    • HSV-1: Primarily spreads through oral contact and leads to infections around the mouth (oral herpes/cold sores) and potentially genital herpes. Most adults are infected with HSV-1.

    • HSV-2: Spreads through sexual contact and primarily causes genital herpes. Many have mild or no symptoms, but painful blisters or ulcers can recur.

  • Medicines can alleviate symptoms but not cure the infection.

A.2. Varicella-Zoster Virus (VZV) Infection

  • Causes chickenpox via invasion of mucosal epithelial cells in the tonsils.

  • Post-infection, the virus remains dormant in dorsal root ganglia and can reactivate later, especially after age 50, leading to disorders like shingles (herpes zoster).

  • Differentiation:

    • Chickenpox: Widespread.

    • Shingles: Dermatomal spread, does not cross the midline.

B. Agents for Herpes Virus & Cytomegalovirus Infections
Varicella Infection Treatment

  • Acyclovir: 20 mg/kg (maximum 800 mg) qid × 5 days.

  • Valacyclovir: 20 mg/kg (maximum, 1 g) tid × 5 days.

  • Zoster Infection Treatment:

    • Acyclovir: 800 mg 5 times daily × 7–10 days.

    • Famciclovir: 500 mg tid × 7 days.

    • Valacyclovir: 1 g tid × 7 days.

  • Administration should ideally commence within 24 hours after rash onset for varicella or within 72 hours for cutaneous zoster to reduce lesion numbers, symptom duration, and viral shedding.

  • Long-term suppression with antiherpes agents can decrease recurrence rates and asymptomatic viral shedding.

  • Differential efficacy observed: Orolabial herpes is less effectively treated than anogenital herpes.

C. Agents to Treat Cytomegalovirus (CMV) Infections

  • CMV infections occur primarily under immunosuppression, leading to severe diseases like retinitis.

  • Treatment Agents:

    • Valganciclovir: 900 mg bid × 21 days for induction, 900 mg daily for maintenance.

    • Ganciclovir: 5 mg/kg q12h × 14–21 days for induction, followed by maintenance at lower daily dosage.

    • Foscarnet: Used for treatment of ganciclovir-resistant CMV cases.

    • Cidofovir: Effective for CMV and other viral infections; dosing adjustments are based on renal function.

  • Main Treatment Goals:

    • Achieve undetectable levels of viral DNA and improve patient health outcomes.

III. ANTI-HIV DRUGS

A. Antiretroviral Agents (ARVs)

  • ARVs are essential in managing HIV infections, primarily preventing the virus’s reproduction while allowing the immune system to recover.

  • ARVs Do Not Cure HIV; consistency can lead to undetectable viral loads and minimized transmission risks.

  • Six Classes of ARVs:

    1. NRTIs

    2. NNRTIs

    3. PIs

    4. Fusion Inhibitors

    5. CCR5 Antagonists

    6. INSTIs

  • Current Antiretroviral Drugs: (Examples)

    • Abacavir (NRTI): 300 mg bid or 600 mg qd (requires HLA-B5701 allele testing).

    • Atazanavir (PI): 400 mg qd with food; watch for liver toxicity.

    • Dolutegravir (INSTI): 50 mg qd, separate dosing from certain medications.

  • Combination Therapy: Administering ARVs from varied classes reduces resistance risks, increases potency, and enhances viral suppression capabilities.

A.1. Nucleoside & Nucleotide Reverse Transcriptase Inhibitors (NRTIs)

  • Mimic DNA building blocks, inhibiting reverse transcriptase and preventing RNA-to-DNA conversion. Notable adverse effects include mitochondrial toxicity (peripheral neuropathy, pancreatitis).

  • Key drugs:

    • Abacavir: May cause hypersensitivity, used in pregnancy.

    • Stavudine: Liver caution; contraindicated with specific drugs.

A.2. Non Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

  • Directly inhibit reverse transcriptase, highly effective against HIV with side effects including CNS effects and drug-drug interactions due to CYP450 metabolism.

A.3. Protease Inhibitors (PIs)

  • Block the protease enzyme, essential for producing mature infectious particles. May induce metabolic syndrome effects.

A.4. Fusion Inhibitors

  • Enfuvirtide (Fuzeon) is a key fusion inhibitor, preventing viral entry into cells.

A.5. Entry Inhibitors (CCR5 Co-Receptor Antagonists)

  • Prescribing CCR5 inhibitors (like Maraviroc) only for patients with CCR5-tropic HIV-1. Increased incident risks for some adverse cardiovascular events are noted.

A.6. Integrase Strand Transfer Inhibitors (INSTIs)

  • Designed to bind to integrase, preventing the insertion of viral DNA into host cells. Generally well tolerated with rare severe events.

A.7. Fixed-Dose Combinations (FDCs)

  • Such combinations simplify treatment in ARV therapy, facilitating patient adherence. Examples include:

    • Abacavir + Lamivudine = Epzicom

    • Bictegravir + Tenofovir Alafenamide + Emtricitabine = Biktarvy

IV. ANTI-HEPATITIS DRUGS

  • Nucleoside/Nucleotide Analogs (NA): Effective primarily in HBV suppression.

  • Interferons (IFN): Include multiple side effects; less than a 50% success response in patients. Recommended for selective use.

  • Goals for Hepatitis B Treatment: Suppression of HBV DNA, reduction of liver disease risks, prevention strategies against cirrhosis and HCC.

D. Antihepatitis C Drugs

  • Targeting specific viral replication stages aims for complete eradication of the virus for hepatitis C management.

  • Direct-acting antivirals (DAAs) like ledipasvir and sofosbuvir have drastically altered treatment outcomes.

D.1. Treatment and Monitoring

  • Treatment lasts typically 8-12 weeks with regular monitoring of HCV RNA levels for instructions on treatment success (SVR).

D.2. Prevention Strategies

  • Emphasize safe practices (e.g., avoiding needle sharing) and timely screenings.

V. ANTI-INFLUENZA

A. Anti-Influenza Agents

  • Include various classes targeting different viral mechanisms.

    • Neuraminidase Inhibitors: Oseltamivir and zanamivir effective against influenza A and B, crucial for early treatment initiation.

    • M2 Ion Channel Inhibitors: Amantadine and Rimantadine target influenza A viruses primarily. High resistance levels noted.

B. Use of Anti-Influenza Agents

  • Indicated to shorten illness severity in influenza and serve as prophylaxis in outbreak situations.

VI. OTHER ANTIVIRAL AGENTS

  • Interferons: For hepatitis infections and specific conditions.

  • Ribavirin: Inhaled form used in severe RSV cases; teratogenic risks noted.

  • Imiquimod: An immune response modifier used topically.

  • Palivizumab: A humanized monoclonal antibody for RSV infection prevention in high-risk groups.

VII. COVID-19 MANAGEMENT

  • Nirmatrelvir-Ritonavir: Oral protease inhibitors combination for treating COVID-19, initiated within 5 days of symptoms for high-risk patients.

  • Remdesivir: Nucleotide analog treatment protocol for hospitalized severe COVID-19 patients.

VIII. REFERENCES

  1. Katzung, B. G. (2018). Basic and Clinical Pharmacology (14th edition). Lange Medical Publications.

  2. Whalen, K., Rajan, R., and Feild, C. (2019). Lippincott Illustrated Reviews Pharmacology (7th edition). Wolters Kluwer.

  3. Lahoz, G. A. (November 2025). Antiviral Agents [PPT].