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Antiviral agents

Last updated: December 23, 2020

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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 article 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.

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 and targets of antiviral drugs
Viral replication cycle Target Antiviral drug
Fusion with host cell
  • Attachment
  • Penetration
Uncoating
Replication of viral genome
Protein synthesis and assembly of viral components
Release of new viruses from host cell
  • Viral budding

Antiviral against influenza [1][2][3]

Agents

Mechanism of action Indications

Adverse effects

Amantadine

Rimantadine

Oseltamivir

Zanamivir

Peramivir

  • Neuraminidase inhibitor: blockage of viral budding and prevention of viral dissemination into the bloodstream by inhibiting neuraminidase enzyme
  • Treatment of influenza A and B (reduces symptom duration if taken within 1–2 days of symptom onset)
  • Prophylaxis of influenza in adults and pediatric patients ≥ 5 years of age

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

Antivirals against herpes [4][5][6]
Agents Mechanism of action Indications Adverse effects Mechanism of antiviral resistance

Acyclovir

Valacyclovir (prodrug of acyclovir with greater oral bioavailability)

Penciclovir

Famciclovir (prodrug of penciclovir with greater oral bioavailability)

  • Guanosine analog (nucleoside analog)
  • HSV/VZV-coded thymidine kinase monophosphorylates the guanosine analog to an active intermediate → phosphorylation by cellular kinases acyclovir triphosphate (ACV-TP)
  • The phosphorylated drug is incorporated into the replicating viral DNA strand → inhibition of viral DNA polymerase via chain termination
  • Selective action in infected cells only with minimal effect on host cells → fewer side effects

Ganciclovir

Valganciclovir (prodrug of ganciclovir with greater oral availability)

  • Systemic treatment of choice for CMV retinitis in immunocompromised patients (e.g., patients with AIDS)
  • CMV prophylaxis in transplant recipients
  • Mutation of viral UL97 kinase
Foscarnet (pyrophosphate analog)

Cidofovir

Fomivirsen
  • Unknown

See “Antiviral treatment of chronic hepatitis C” and “Antiviral treatment of chronic hepatitis B.”

Antivirals against both hepatitis B and C

Antivirals against both hepatitis B and C [7][8]
Agents Mechanism of action Indications Contraindications Adverse effects

Pegylated interferon-α and interferon-α

  • Antiviral and immunomodulatory effect via intercellular and intracellular mechanisms

Antivirals against hepatitis B

Antivirals against hepatitis B only [8]
Agents Mechanism of action Indications Adverse effects

Tenofovir

Adefovir

Entecavir

Lamivudine

Telbivudine

Antivirals against hepatitis C

Antivirals against hepatitis C only [7]
Agents Mechanism of action Indications Adverse effects
Ribavirin
Direct acting antivirals (DAAs)

Glecaprevir

  • NS3/4A protease inhibitors
  • Inhibition of NS3/4A (an HCV serine protease required for viral replication) → ↓ viral replication
Grazoprevir

Paritaprevir

Simeprevir

Voxilaprevir

Daclatasvir

  • Non-nucleoside NS5A polymerase inhibitors
  • Exact mechanism of action is unknown
  • Inhibition of the viral NS5A phosphoprotein, which is essential for replication → prevention of HCV RNA replication

Elbasvir

Ledipasvir

Ombitasvir

Pibrentasvir

Velpatasvir

Dasabuvir

Sofosbuvir

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

  1. Lanier ER, Foster S, Brundage T, et al. Analysis of mutations in the gene encoding cytomegalovirus DNA polymerase in a phase 2 clinical trial of brincidofovir prophylaxis. J Infect Dis. 2016; 214 (1): p.32-35. doi: 10.1093/infdis/jiw073 . | Open in Read by QxMD
  2. Prichard MN. Function of human cytomegalovirus UL97 kinase in viral infection and its inhibition by maribavir. Rev Med Virol. 2009; 19 (4): p.215-229. doi: 10.1002/rmv.615 . | Open in Read by QxMD
  3. He Z, He YS, Kim Y, et al. The human cytomegalovirus UL97 protein is a protein kinase that autophosphorylates on serines and threonines.. J Virol. 1997; 71 (1): p.405-11.
  4. HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C. https://www.hcvguidelines.org/sites/default/files/full-guidance-pdf/AASLD-IDSA_HCVGuidance_August_27_2020.pdf. Updated: August 27, 2020. Accessed: December 3, 2020.
  5. Katzung B,Trevor A. Basic and Clinical Pharmacology. McGraw-Hill Education ; 2014
  6. UpToDate. Rimantadine: Drug information. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/rimantadine-drug-information?source=preview&search=Rimantadine&anchor=F216956#F216956.. Accessed: February 21, 2017.
  7. Zanamivir. https://www.drugs.com/ppa/zanamivir.html. . Accessed: February 21, 2017.
  8. Stiver G. The treatment of influenza with antiviral drugs. CMAJ. 2003; 168 (1): p.49-57.