Antiviral agents

Information about Antiviral agents

The antivirals are a large and diverse group of agents that are typically classified by the virus infections for which they are used, their chemical structure and their mode of action. Most antiviral agents have been developed in the last 20 to 25 years, many as a result of the major research efforts to develop therapies and means of prevention of human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS). Some of the agents developed to treat HIV infection, AIDS and its complications were found to also inhibit other viruses, and the novel approaches taken in development of antiretroviral therapy have been applied to develop therapies of other viral infections.

HIV antiviral agents

Antiretroviral Agents for HIV Infection. The antiretroviral agents include nucleoside analogues with reverse transcriptase activity (such as tenofovir, emtricitabine, lamivudine, abacavir, stavudine, didanosine, zidovudine), the nonnucleoside reverse transcriptase inhibitors (such as delavirdine, efavirenz, etravirine, nevirapine and rilpivirine), protease inhibitors (atazanavir, darunavir, indinavir, ritonavir, tipranavir and many others), and miscellaneous agents such as maraviroc that inhibits binding of the HIV virus its T cell receptor (CCR5 coreceptor antagonist), enfuvirtide that blocks the uptake of HIV into cells (fusion inhibitor), and integrase inhibitors (raltegravir, elvitegravir and dolutegravir) that block the integrase enzyme of HIV.

Hepatitis B antiviral agents

Hepatitis B Agents. The agents active against hepatitis B virus (HBV) include several nucleoside analogues that are also active against and used to treat HIV infection (tenofovir, emtricitabine, lamivudine), as well as agents that are poorly if at all active against HIV (adefovir, entecavir and telbivudine). Alpha interferon and peginterferon (its long acting pegylated form) are also active against hepatitis B, but are no longer commonly used for this indication.

Hepatitis C antiviral agents

Hepatitis C Agents. The agents active against hepatitis C virus (HCV) include interferon alfa (1992) and peginterferon (2000) which are used in combination with ribavirin, a nucleoside analogue that potentiates the effects of interferon against hepatitis C by unclearly defined mechanisms. Progress in treatment of hepatitis C began to accelerate in 2010 with the introduction of the first direct acting anti-HCV agents, two HCV-specific protease inhibitors: boceprevir and telaprevir. While combinations of these protease inhibitors with peginterferon and ribavirin yielded high response rates (60% to 75%), the regimens were poorly tolerated, expensive and prolonged (courses were typically for 48 weeks). Beginning in 2013, new direct acting anti-HCV agents with potent activity against different regions of the virus were introduced, which in combination obviated the need for interferon and yielded sustained response rates of greater than 90% with 12 to 24 weeks of treatment.

The direct acting agents were directed against 3 components of HCV: HCV protease (NS3) inhibitors included simeprevir [2013], paritaprevir [2015], grazoprevir [2016] and glecaprevir [2017]); HCV RNA polymerase (NS5B) inhibitors included sofosbuvir [2013, a nucleoside analogue] and dasabuvir [2015, a non-nucleoside inhibitor]; and, HCV NS5A inhibitors included daclatasvir [2015], elbasvir [2016], lepidasvir [2014], ombitasvir [2015], velpatsvir [2016] and pibrentasvor [2017].

Combinations of 2 or 3 of these achieve sustained response rates of greater than 90%, with relatively short courses of therapy (8, 12 to 16 weeks) and without the need of interferon and its difficult and dose-limiiting side effects. These combinations are available under brand names such as Harvoni, Technive, Viekira Pak, Zepatier, Epclusa and Mavyret. Newer agents and different combination products are likely to be developed in the near future. Many of the earlier combinations are likely to be discontinued as newer regimens are more effective, better tolerated and active against all genotypes and in patients with renal disease, HIV infection or cirrhosis.

Herpes virus agents

Herpes Virus Agents. The agents active against various herpes viruses (herpes simplex, varicella zoster, cytomegalovirus) include acyclovir and related acyclic nucleoside analogues such as valacyclovir, cidofovir, famciclovir, ganciclovir and valganciclovir, and other miscellaneous agents such as foscarnet.

Influenza agents

Influenza Agents. The agents active against influenza A virus include amantadine and rimantadine which act on viral uncapping, and three neuraminidase inhibitors osteomavir (oral), zanamivir (by inhalation) and peramivir (intravenous). These agents are used during influenza outbreaks, generally for a brief period only, but are effective in prevention as well as amelioration of influenza infection.

The following drug records are antiviral agents:

Drugs for HIV Infection, in the Subclass Antiretroviral Agents

• Fusion Inhibitors (HIV)
  • Enfuvirtide, Maraviroc

• Integrase Inhibitors (HIV)
  • Dolutegravir, Elvitegravir, Raltegravir

• Monoclonal Antibodies
  • Ibalizumab

• Nonnucleoside Reverse Transcriptase Inhibitors (HIV)
  • Delavirdine, Efavirenz, Etravirine, Nevirapine, Rilpivirine

• Nucleoside Analogues (HIV)
  • Abacavir, Didanosine, Emtricitabine, Lamivudine, Stavudine, Tenofovir, Zidovudine

• Protease Inhibitors (HIV)
  • Amprenavir, Atazanavir, Darunavir, Fosamprenavir, Indinavir, Lopinavir, Nelfinavir, Ritonavir, Saquinavir, Tipranavir

Drugs for Hepatitis B

• Alpha Interferon, Adefovir, Emtricitabine, Entecavir, Lamivudine, Telbivudine, Tenofovir

Drugs for Hepatitis C

• Interferon Based Therapies
  • Alpha Interferon and Peginterferon, Ribavirin

HCV NS5A Inhibitors

• Daclatasvir, Elbasvir, Ledipasvir, Ombitasvir, Pibrentasvir, Velpatasvir

HCV NS5B Inhibitors (Polymerase inhibitors)

• Dasabuvir, Sofosbuvir

HCV Protease Inhibitors

• Asunaprevir, Boceprevir, Glecaprevir, Grazoprevir, Paritaprevir, Simeprevir, Telaprevir, Voxilaprevir

Combination Therapies

• Epclusa, Harvoni, Mavyret, Technive, Viekira Pak, Vosevi, Zepatier

Drugs for Herpes Virus

• infections (HSV), CMV, others

Acyclovir, Cidofovir, Famciclovir, Foscarnet, Ganciclovir, Valacyclovir, Valganciclovir

Drugs for Influenza

• Amantadine, Oseltamivir, Peramivir, Rimantadine, Zanamivir

• Dailymed label info on Antiviral agents
• FDA Antiviral agents

Antiviral agents Resources
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