• Clinical science

Antiviral agents

Abstract

Antivirals are a class of medication 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 currently available antiviral drugs are used in the therapy of infections caused by HIV, herpes viruses, hepatitis B and C viruses, and influenza A and B viruses. Owing to the fact that viruses are obligate, intracellular parasites, it is difficult to find targets for the drug that interfere with viral replication without also harming the host cells. Unlike other antimicrobials, none of the antiviral drugs deactivate or destroy the microbe (in this case, the virus); rather they act by only inhibiting replication. Thus, they prevent the viral load from increasing to a point where it could cause pathogenesis, leaving it susceptible to neutralization by the body's innate immune mechanisms. This learning card provides an overview of the most important antiviral agents. For further details on the use of antiretroviral agents in the treatment of HIV, referred to as highly active antiretroviral therapy (HAART), see section on “HIV therapy” in the HIV learning card.

Basics

Viruses are obligate pathogens, which depend on host-cell machinery for replication. Most antiviral agents act on key proteins required for viral replication and are developed, such that they can achieve high levels of selectivity. Since viral replication usually peaks with the onset of clinical symptoms, rapid diagnosis is essential to ensure that antiviral agents are administered in a timely manner.

Overview of steps of viral replication with corresponding antiviral drugs

Starting point in viral replication cycle Antiviral drug
Attachment and penetration of the virus to the host cell; release of nucleic acid
Replication of the viral genome
  • Starting point for reverse transcriptase (e.g., in HIV infection)
Translation of viral mRNA
Assembly of viral components
Removal and release of new viruses from the host cell

References:[1]

Antivirals against influenza viruses

Agents

Mechanism of action

Adverse effects

Areas of application

Amantadine

Rimantadine

Ion channel blocker

Oseltamivir

Zanamivir

Neuraminidase inhibitor

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

References:[2][3][4]

Antivirals against Herpes viruses

Agents Mechanism of action Mechanism of antiviral resistance Adverse effects Areas of application

Acyclovir

Penciclovir

Valacyclovir

Famciclovir

  • Mutated viral thymidine kinase

Active infections with

Ganciclovir

Valganciclovir

  • Mutated viral UL97 kinase
  • Hematological adverse effects
    • Pancytopenia (additive effect when co-administered with NRTIs)
  • Gastrointestinal adverse effects
  • CNS
Foscarnet
  • Directly inhibits viral DNA polymerases (pyrophosphate analog)
  • Does not require activation by viral kinase
Cidofovir
  • Directly inhibits viral DNA polymerases
  • Does not require activation by viral kinase
Fomivirsen
  • Unknown

Adverse effects after intraocular injection:

References:[5][6][7]

Antivirals against hepatitis B and C

Agents

Mechanism of action

Adverse effects

Areas of application

Antivirals against hepatitis B

Tenofovir

Adefovir

Nucleotide analog
  • Nephrotoxicity
  • Headache and abdominal pain
  • Disease exacerbation is possible.

Lamivudine

Entecavir

Telbivudine

Nucleoside analog: inhibition of reverse transcriptase
Antivirals against hepatitis B and C
(PEG‑) interferon-α Antiviral and immunomodulatory via intercellular and intracellular mechanisms

Antivirals against hepatitis C

Ribavirin Guanosine analog (nucleoside inhibitor): inhibition of inosine monophosphate dehydrogenase → prevents synthesis of guanine nucleosides
Simeprevir Protease inhibitors
Ledipasvir Non-nucleoside polymerase (NS5A) inhibitor
Sofosbuvir Non-nucleoside polymerase (NS5B) inhibitor
  • Headache
  • Fatigue
  • Contraindication: severe renal insufficiency
Velpatasvir Non-nucleoside polymerase (NS5A) inhibitor

References:[1][8][9]

last updated 11/12/2018
{{uncollapseSections(['vubAGv', 'vBXAc00', '9BXN100', 'DBX1100', 'wBXh100'])}}