Antiviral drug

Antiviral drugs are a class of medications used to treat infections caused by viruses. They form a major subgroup of antimicrobial agents, alongside antibacterials, antifungals and antiparasitics. Most antiviral drugs are designed to target specific viruses, although some broad-spectrum antivirals act against multiple viral families. Because viruses replicate inside host cells and rely heavily on host machinery, antiviral development poses unique challenges: drug targets must interfere with viral replication without significantly harming the host organism. Antivirals differ from virucides, which are non-pharmacological agents that deactivate or destroy viral particles outside or inside the body; some plants such as eucalyptus and tea tree species naturally produce virucidal compounds.
Modern antiviral therapies concentrate mainly on HIV, members of the Herpesviridae family, hepatitis B and C viruses, and influenza A and B. Their development has been driven by advances in molecular virology, genome sequencing, recombinant protein production and high-throughput screening technologies.

Medical uses

Antiviral medications may be used both therapeutically and prophylactically. Many of the most widely prescribed antivirals are designed to suppress chronic viral infections such as HIV and hepatitis B. Others shorten the duration or severity of acute illnesses, as with influenza treatments, or prevent complications in high-risk groups. Variation among viral strains remains a major obstacle to vaccine and antiviral development, as viruses—particularly RNA viruses—mutate rapidly.
The field expanded significantly following the rise of HIV/AIDS, which created urgent clinical demand for drugs that inhibit viral replication. Early antivirals discovered in the 1960s targeted herpes simplex virus, but these were developed largely through trial-and-error screening. Only after viral genomes were deciphered in the 1980s did rational drug design based on viral structure and function become possible.

Antiviral drug design

Modern antiviral development centres on identifying specific viral proteins that can be selectively disabled. The ideal targets are enzymes or structural proteins unique to the virus, reducing off-target toxicity. Targets shared across many strains—or at least within a viral family—improve the likelihood that a drug will retain effectiveness despite viral evolution.
Candidate drugs may be adapted from known pharmaceuticals or designed de novo using computational chemistry. Target proteins are typically expressed in laboratory cell lines through genetic engineering, enabling researchers to evaluate binding interactions and inhibitory effects rapidly.
Because viral life cycles follow a general pattern—attachment, entry, uncoating, genome replication, assembly and release—drug development often focuses on these stages.

Antivirals acting before cell entry

A key strategy is preventing viruses from entering host cells. Viruses bind to specific receptor molecules on the host cell surface via virus-associated proteins (VAPs). Drugs may inhibit entry by:

• Mimicking VAPs and binding to cellular receptors
• Mimicking cellular receptors and binding to VAPs

This approach is technically challenging and often expensive because identifying effective mimics, including anti-idiotypic antibodies, requires extensive screening.

Entry inhibitors

Entry inhibitors have been most explored for HIV. HIV targets helper T cells via CD4 and a co-receptor such as CCR5. While attempts to block HIV–CD4 binding have been insufficient, CCR5-blocking strategies have achieved more success. Enfuvirtide, a synthetic peptide that prevents HIV–cell membrane fusion, was the first entry inhibitor to receive regulatory approval.
Entry blockers may offer advantages over enzyme inhibitors: they could reduce viral spread both within infected individuals and between individuals, and viral resistance may evolve more slowly.

Uncoating inhibitors

Following entry, many viruses must uncoat to release their genomes. Drugs that interfere with this process can halt infection. Amantadine and rimantadine inhibit the uncoating of influenza A viruses. Pleconaril targets a conserved pocket in rhinoviruses, preventing uncoating; it also has activity against certain enteroviruses.
Although rhinoviruses are diverse, they mutate less rapidly than influenza viruses. Research into multivalent vaccines combining numerous inactivated rhinovirus types has shown promise in stimulating broad immunity in animal models.

Antivirals acting during viral synthesis

Once inside a cell, viruses replicate their genomes and produce viral proteins using host resources. Drugs can target replication enzymes or interfere with viral nucleic acid synthesis.

Reverse transcription inhibitors

A widely used class, especially in HIV treatment, comprises nucleoside and nucleotide analogues. These resemble the natural building blocks of DNA or RNA but terminate chain elongation or introduce mutations when incorporated into viral genomes. Combination therapy using multiple inhibitors reduces the likelihood of resistance.

Broader approaches and natural products

Some mushroom species contain synergistic antiviral compounds, and extracts have demonstrated broad-spectrum activity in vitro. However, translating such findings into practical, standardised antivirals remains a distant prospect.
Because many viruses share similar replication mechanisms, researchers continue to investigate targets that could lead to broad-spectrum antivirals, including polymerase inhibitors and protease inhibitors that function across diverse viral families.

Viral life cycle context

Despite substantial variation among viruses, their life cycles share key steps:

1. Attachment to a host cell
2. Entry and uncoating
3. Genome replication and viral protein synthesis
4. Assembly of new virions
5. Release to infect new cells