Brief Guide to Antiviral Drugs

Viruses are intracellular parasites that co-opt cell machinery to reproduce. During reproduction, viruses destroy cells and go on to infect other cells. 

During the 1950s, while researching possible treatments for cancer, scientists discovered chemical compounds that could inhibit viral DNA replication. During the 1980s and 1990s, after HIV became a problem, antiviral medications experienced a renaissance. Today, antiviral medications are used to treat many diseases.

In order to be effective, antiviral medications must target either viral entry or exit or target the virus while it's inside a cell. Antiviral medications must also be specific so as not to cause systemic toxicity. Furthermore, antiviral drugs should be potent and stable.

Here are brief descriptions of some of the antiviral drugs currently available.

Antiviral Drugs Used to Treat Herpes Simplex Virus (HSV) and Varicella-Zoster Virus (VZV)

The three main drugs used to treat herpes simplex (causes herpes and cold sores) and varicella zoster viruses (causes chickenpox and shingles) are acyclovir, valacyclovir, and famciclovir.

All three of these drugs are relatively safe and have similar mechanisms of action. For instance, they all work by binding to viral DNA polymerase, an enzyme used to replicate viral DNA. Of note, because valacyclovir (Valtrex) and famciclovir reach higher blood concentrations, these 2 drugs are most effective in treating shingles. 

Drugs Used to Treat Genital Warts (Human Papillomavirus)

Drugs used to treat genital warts include (topical) imiquimod.

Antiviral Drugs Used to Treat Influenza (The Flu)

Influenza is a common cause of flu during the winter season. Fortunately, we have vaccines that confer immunity to the seasonal flu. It's important to obtain your yearly flu shot because sometimes flu can become pneumonia, and sometimes pneumonia can kill--especially among children and older people. 

Drugs like Tamiflu (oseltamivir) and zanamivir (Relenza) can be used to prevent symptoms of the flu and shorten the length of illness. In addition to drugs used to prevent influenza disease or pathology, there are also drugs which disrupt viral machinery after infection with influenza including amantadine, rimantadine, oseltamivir, and zanamivir.

Antiviral Drugs Used to Treat Cytomegalovirus (CMV) Infections

Cytomegalovirus infection typically occurs in people who are very sick (think immunocompromised by AIDS or organ transplant). Like the varicella-zoster virus, which causes herpes zoster (shingles), most of us harbor the cytomegalovirus, but the virus will only reactivate if your immune system is run down.

In those who are already pretty sick, symptoms of cytomegalovirus infection affect many organ systems and include:

• Retinitis (viral infection of light-sensing retina in the back of the eye_
• Esophagitis (inflammation of the food tube)
• Colitis (inflammation of the colon)
• Brain and spinal cord (CNS) infection
• Pneumonitis (infection of the lungs)

Drugs used to treat cytomegalovirus infection include valganciclovir, ganciclovir, foscarnet, and cidofovir. (Because of greater bioavailability, use of valganciclovir has largely replaced ganciclovir.) Like other antiviral drugs, antiviral drugs used to treat cytomegalovirus in part affect viral enzymes like viral DNA and RNA polymerase.

Antiviral Drugs Used to Treat Hepatitis

Various antiviral drugs are used to treat hepatitis B and hepatitis C. Most of these drugs directly affects viral reproduction.

Hepatitis C may be treated with direct acting antivirals, which are given as pills for 12 weeks or more. These include Epclusa (sofosbuvir/velpatasvir), Harvoni (sofosbuvir, ledipasvir), Mavyret (glecapravir, pibrentasvir), Sovaldi (sofosbuvir), Vosevi (sofosbuvir, velpatasvir, voxilaprevir), and Zepatier (grazoprevir + elbasvir).

Hepatitis B treatment may include the antivirals Baraclude (entecavir), Epivir (lamivudine), Hepsera (adefovir), Tyzeka (telbivudine), Vemlidy (tenofovir AF), and Viread (tenofovir DF).

Interferon, probably the most common drug associated with the treatment of hepatitis infection, works by complex mechanisms that encompass antiviral, immunomodulatory (managing the immune response), and antiproliferative (preventing spread) actions. 

Antiviral Drugs Used to Treat HIV

During the past three decades, there have been great improvements in the treatment of HIV infection, and more people with the disease are living AIDS-free. (AIDS is a more severe form of HIV infection diagnosed after the level of white blood cells in the blood drops dangerously low.)

There are several types of antiretroviral drugs:

• Protease inhibitors: These include Reyataz (atazanavir), Prezista (darunavir), Lexiva (fosamprenavir), Lopinavir (available in the combination drug Kaletra), Norvir (ritonavir), and Aptivus (tipranavir)
• Fusion inhibitors: Fuzeon (enfuvirtide)
• Nucleoside/nucleotide reverse transcriptase inhibitors: Include Ziagen (abacavir), Emtriva (emtricitabine), Epivir (lamivudine), Viread (tenofovir disoproxil fumarate), Retrovir (zidovudine)
• Non-nucleoside reverse transcriptase inhibitors: Include Pifeltro (doravirine), Sustiva (efavirenz), Intelence (etravirine), Viramune, Viramune XR (nevirapine), Edurant (rilpivirine) 
• Entry inhibitors (prevent viral entry into the cell): Include Trogarzo (ibalizumab-uiyk), Rukobia (fostemsavir), and Sunlenca (lenacapavir)
• HIV integrase strand transfer inhibitors (INSTIs): Include Isentress (raltegravir), Tivicay (dolutegravir), Vitekta (elvitegravir), Triumeq (dolutegravir + abacavir + lamivudine), Stribild (elvitegravir + cobicistat + tenofovir + emtricitabine), Genvoya (elvitegravir + cobicistat + tenofovir AF + emtricitabine), Juluca (dolutegravir + rilpivirine), Biktarvy (bictegravir + tenofovir AF + emtricitabine)

These drugs target various stages of the viral replication cycle. Of note, retroviruses replicate by means of reverse transcription.

Please note that this list is by no means comprehensive, and there are several other drugs that treat viral infections. Of equal note, mechanisms of action are far more complicated than presented here. Instead, please appreciate this article as a primer on the topic.