Table of Contents

Anti-Viral Drugs

Viruses are obligate intracellular parasites that depend entirely on host cellular machinery for replication. Unlike bacteria, viruses lack a complete metabolic system and do not possess a cell wall or independent metabolic processes. This makes antiviral therapy particularly challenging because drugs must selectively target viral replication without damaging host cells.

Another important challenge in antiviral therapy is that clinical symptoms usually appear after viral replication has already occurred, limiting the effectiveness of drugs that block replication. However, several antiviral agents are effective when used early in infection or as prophylaxis.

Antiviral drugs are classified based on the type of viral infection they target, including:

  • Respiratory viral infections

  • Hepatic viral infections (Hepatitis)

  • Herpesvirus infections

  • HIV infection

  • Other viral diseases

I. Treatment of Respiratory Viral Infections

Respiratory viral infections include:

  • Influenza A

  • Influenza B

  • Respiratory Syncytial Virus (RSV)

Vaccination remains the preferred preventive strategy for influenza, but antiviral therapy is used in high-risk individuals, during outbreaks, or when vaccination is contraindicated.

1. Neuraminidase Inhibitors

Drugs:

  • Oseltamivir

  • Zanamivir

Mechanism of Action

Influenza viruses possess a surface enzyme called neuraminidase, which allows newly formed virions to detach from infected host cells. Neuraminidase inhibitors block this enzyme, preventing the release and spread of viral particles.

This action:

  • Reduces viral spread from cell to cell

  • Decreases severity and duration of symptoms

  • Is most effective when started within 24–48 hours of symptom onset

Pharmacokinetics

  • Oseltamivir is an orally active prodrug converted in the liver to its active form.

  • Zanamivir is administered via inhalation because it is not effective orally.

  • Both drugs are eliminated primarily through renal excretion.

Adverse Effects

Oseltamivir:

  • Nausea

  • Vomiting

  • Gastrointestinal discomfort

Zanamivir:

  • Bronchospasm

  • Caution in asthma and COPD patients

Resistance

Resistance occurs due to mutations in the neuraminidase enzyme but resistant strains often show reduced virulence.

2. Adamantane Antivirals

Drugs:

  • Amantadine

  • Rimantadine

These drugs are effective only against Influenza A and are currently not recommended in many regions due to widespread resistance.

Mechanism of Action

They block the viral M2 ion channel protein, preventing viral uncoating inside host cells.

Pharmacokinetics

  • Well absorbed orally

  • Amantadine crosses the blood-brain barrier

  • Excreted renally

Adverse Effects

Amantadine:

  • CNS toxicity (insomnia, dizziness, hallucinations)

  • Ataxia

  • Seizures

Rimantadine:

  • Fewer CNS effects

  • Gastrointestinal upset

3. Ribavirin

Ribavirin is a broad-spectrum antiviral effective against both RNA and DNA viruses.

Clinical Uses

  • Severe RSV infection in infants

  • Chronic Hepatitis C (with interferon)

Mechanism of Action

After phosphorylation to ribavirin triphosphate, it:

  • Inhibits guanosine triphosphate formation

  • Blocks viral RNA-dependent RNA polymerase

  • Prevents viral mRNA capping

Pharmacokinetics

  • Available orally and via inhalation

  • Renal excretion

  • Better absorption with fatty meals

Adverse Effects

  • Dose-dependent hemolytic anemia

  • Elevated bilirubin

  • Teratogenic (contraindicated in pregnancy)

II. Treatment of Hepatic Viral Infections

Chronic hepatitis B and C are major causes of:

  • Cirrhosis

  • Chronic liver disease

  • Hepatocellular carcinoma

1. Interferons

Types:

  • Interferon-α

  • Peginterferon-α

Mechanism of Action

Interferons induce host cell enzymes that:

  • Inhibit viral RNA translation

  • Promote degradation of viral mRNA

Pharmacokinetics

  • Not orally active

  • Administered subcutaneously or intramuscularly

  • Pegylation increases half-life and improves tolerability

Adverse Effects

  • Flu-like symptoms

  • Bone marrow suppression

  • Depression

  • Thyroid disorders

  • Autoimmune reactions

2. Nucleoside/Nucleotide Analogues for Hepatitis B

Drugs include:

  • Lamivudine

  • Adefovir

  • Entecavir

  • Telbivudine

  • Tenofovir

These agents:

  • Inhibit viral DNA polymerase

  • Cause chain termination

  • Suppress viral replication

Important adverse effects:

  • Nephrotoxicity (Adefovir)

  • Myopathy (Telbivudine)

  • Renal dysfunction (Tenofovir)

III. Treatment of Herpesvirus Infections

Herpes viruses cause:

  • Cold sores (HSV-1)

  • Genital herpes (HSV-2)

  • Varicella-zoster (shingles)

  • CMV infections

1. Acyclovir

Prototypical anti-herpetic drug.

Mechanism of Action

  • Activated by viral thymidine kinase

  • Converted to acyclovir triphosphate

  • Inhibits viral DNA polymerase

  • Causes DNA chain termination

Uses

  • Genital herpes

  • HSV encephalitis

  • Varicella-zoster

  • Prophylaxis in transplant patients

Adverse Effects

  • Renal toxicity (high IV doses)

  • Nausea

  • Headache

Valacyclovir has better oral bioavailability.

2. Ganciclovir

More active against CMV.

Major toxicity:

  • Severe neutropenia

  • Bone marrow suppression

Valganciclovir is the oral prodrug.

3. Foscarnet

  • Direct DNA polymerase inhibitor

  • Used for acyclovir-resistant HSV

  • Causes nephrotoxicity and electrolyte imbalance

IV. Treatment of HIV Infection (HAART)

Modern HIV therapy uses combination regimens called Highly Active Antiretroviral Therapy (HAART).

Goals:

  • Suppress HIV RNA replication

  • Restore CD4 count

  • Reduce mortality

  • Improve quality of life

Drug Classes:

  1. NRTIs

  2. NNRTIs

  3. Protease Inhibitors

  4. Entry Inhibitors

  5. Integrase Inhibitors

Preferred initial therapy:
Two NRTIs + one PI/NNRTI/Integrase inhibitor

NRTIs (Nucleoside Reverse Transcriptase Inhibitors)

Examples:

  • Zidovudine (AZT)

  • Lamivudine

  • Tenofovir

  • Abacavir

  • Emtricitabine

Mechanism

  • Lack 3′-OH group

  • Cause DNA chain termination

  • Inhibit reverse transcriptase

Common Toxicities

  • Lactic acidosis

  • Hepatomegaly

  • Peripheral neuropathy

  • Bone marrow suppression (AZT)

  • Hypersensitivity (Abacavir – HLA-B*5701 screening required)

NNRTIs

Examples:

  • Efavirenz

  • Nevirapine

  • Rilpivirine

Mechanism:

  • Bind to reverse transcriptase at allosteric site

  • Noncompetitive inhibition

Adverse effects:

  • Rash

  • Hepatotoxicity

  • CNS symptoms (Efavirenz – vivid dreams)

Protease Inhibitors

Examples:

  • Ritonavir

  • Darunavir

  • Atazanavir

  • Lopinavir

Mechanism:

  • Inhibit HIV protease

  • Prevent maturation of viral particles

Adverse effects:

  • Hyperlipidemia

  • Hyperglycemia

  • Fat redistribution (buffalo hump)

  • Drug interactions (CYP450 inhibition)

Integrase Inhibitors

Examples:

  • Raltegravir

  • Dolutegravir

  • Elvitegravir

Mechanism:

  • Prevent integration of viral DNA into host genome

Advantages:

  • Well tolerated

  • Fewer metabolic effects

Conclusion

Antiviral pharmacology is complex due to:

  • Viral dependence on host cells

  • Rapid mutation and resistance

  • Narrow therapeutic windows

Understanding:

  • Mechanism of action

  • Pharmacokinetics

  • Adverse effects

  • Resistance patterns

is essential for safe and effective clinical practice.