• Clinical science

Antiviral agents

Summary

Antivirals are a class of medications that are used to treat viral infections. Most viral infections resolve spontaneously in immunocompetent individuals. The aim of antiviral therapy is to minimize symptoms and infectivity as well as to shorten the duration of illness. These drugs act by arresting the viral replication cycle at various stages. Currently, antiviral therapy is available only for a limited number of infections. Most of the antiviral drugs currently available are used to treat infections caused by HIV, herpes viruses, hepatitis B and C viruses, and influenza A and B viruses. Because viruses are obligate, intracellular parasites, it is difficult to find drug targets that interfere with viral replication without also harming the host cells. Unlike other antimicrobials, antiviral drugs do not deactivate or destroy the microbe (in this case, the virus) but act by inhibiting replication. In this way, they prevent the viral load from increasing to a point where it could cause pathogenesis, allowing the body's innate immune mechanisms to neutralize the virus. This learning card provides an overview of the most commonly used antiviral agents. For more information on antiretroviral agents used in the treatment of HIV, which is known as highly active antiretroviral therapy (HAART), see HIV therapy.

Viral replication cycle and targets of antiviral drugs

  • Viruses are obligate pathogens, which depend on host-cell machinery for replication.
  • Most antiviral agents target key enzymes required for viral replication (see viral life cycle for details).
Viral replication cycle Target Antiviral drug
Fusion with host cell
  • Attachment
  • Penetration
  • Fusion inhibitor (e.g., enfuvirtide)*
Uncoating
Replication of viral genome
  • DNA integration (integrase)
  • Integrase inhibitors (e.g., dolutegravir, elvitegravir, raltegravir)*
Protein synthesis and assembly of viral components
Release of new viruses from host cell
  • Viral budding
* See HIV therapy for details.

References:[1]

Antivirals against influenza viruses

Agents

Mechanism of action

Adverse effects

Indications

Amantadine

Rimantadine

  • M2 ion channel blocker
  • Weak NMDA receptor antagonist

Oseltamivir

Zanamivir

Peramivir

  • Gastrointestinal symptoms
  • Headache
  • Upper respiratory tract infections
  • Influenza A and B
  • Prophylaxis of influenza in adults and pediatric patients 5 years and older

In influenza A and B, rapid administration of neuraminidase inhibitors within 1–2 days of symptom onset is vital to reduce the duration of illness and alleviate symptoms.

References:[2][3][4]

Antivirals against herpes viruses

Agents Mechanism of action Mechanism of antiviral resistance Adverse effects Indications

Acyclovir

Valacyclovir (prodrug of acyclovir with greater oral bioavailability)

Penciclovir

Famciclovir (prodrug of penciclovir with greater oral bioavailability)

  • Guanosine analog (nucleoside analog): initially HSV/VZV-coded thymidine kinase monophosphorylates the guanosine analog to an active intermediate, which is then phosphorylated by cellular kinases
  • The phosphorylated drug is incorporated into the replicating viral DNA strand and inhibits the viral DNA polymerase → termination of viral DNA synthesis
  • Selective action in infected cells onlyminimal effect on host cells' DNA replication
  • Mutated viral thymidine kinase

Ganciclovir

Valganciclovir (prodrug of ganciclovir with greater oral availability)

  • Guanosine analog (nucleoside analog): initially phosphorylated to 5' monophosphate by the CMV-coded UL97 kinase → further phosphorylated to triphosphate by cellular kinases
  • The phosphorylated drug is incorporated into the replicating viral DNA strand and inhibits the viral DNA polymerase → termination of viral DNA synthesis
  • Lower selectivity than acyclovir and penciclovir → can affect host cell's DNA replication
  • Mutated viral UL97 kinase
  • Hematological abnormalities
    • Pancytopenia (additive effect when administered with NRTIs)
  • Nephrotoxicity
  • Gastrointestinal symptoms
  • CNS
Foscarnet (pyrophosphate analog)
  • Viral DNA/RNA polymerase inhibitor and HIV reverse transcriptase inhibitor: direct inhibition of viral DNA polymerases by binding to the pyrophosphate binding site of enzyme
  • Does not require activation by viral kinase
Cidofovir
Fomivirsen
  • Unknown

References:[5][6][7]

Antivirals against hepatitis B and C

Antivirals against both hepatitis B and C

See antiviral treatment of chronic hepatitis C and antiviral treatment of chronic hepatitis B for details.

Agents Mechanism of action Adverse effects Indications

Pegylated interferon-α and interferon-α

  • Antiviral and immunomodulatory effect via intercellular and intracellular mechanisms : inhibits viral protein synthesis, promotes the breakdown of viral RNA, and induces the increased expression of MHC class I molecules

Antivirals against hepatitis B

See antiviral treatment of chronic hepatitis B for details.

Agents Mechanism of action Adverse effects Indications

Tenofovir

Adefovir

Entecavir

Lamivudine

Telbivudine

  • Nucleoside analog: inhibition of reverse transcriptase

Antivirals against hepatitis C [8]

Agents Mechanism of action Adverse effects Indications
Ribavirin
Direct acting antivirals (DAAs) Simeprevir
Grazoprevir
Ledipasvir
Ombitasvir
Velpatasvir
Sofosbuvir
Dasabuvir

Protease inhibitors used to treat HIV end in “navir.” Protease inhibitors used to treat HCV end in “previr.”

References:[1][9][10][8]