Antiviral Drugs: Videos & Practice Problems

Antiviral drugs target viruses by exploiting selective toxicity, focusing on viral life cycle stages: entry inhibitors block virus attachment to host cell receptors; replication inhibitors use nucleoside analogs to disrupt viral DNA or RNA polymerases unique to viruses like HIV, herpes, and COVID-19; assembly and exit inhibitors, including protease and neuraminidase inhibitors, prevent viral protein processing and release. Additionally, interferons stimulate innate immunity by enhancing antiviral protein production. These strategies reduce viral load and symptoms but often do not cure infections, highlighting the complexity of treating diverse viruses such as retroviruses, DNA, and RNA viruses.

Antiviral Drugs

Antiviral drugs are designed to combat viral infections by targeting specific stages of the virus life cycle, but unlike antibiotics or antifungals, they typically do not cure infections outright. Instead, antivirals often work by slowing the progression of the infection, reducing symptoms, and limiting the spread of the virus. This is largely due to the challenge of achieving selective toxicity, as viruses replicate inside host cells and utilize the host's cellular machinery, making it difficult to target the virus without harming the host.

Viruses vary widely in structure and function, which complicates antiviral drug development. For example, HIV is a retrovirus, herpes is a DNA virus, and influenza and COVID-19 are RNA viruses. Despite these differences, antiviral drugs can be grouped based on the stage of the viral life cycle they target: entry inhibitors, replication inhibitors, assembly and exit inhibitors, and immune system stimulators.

Entry inhibitors, such as maraviroc used for HIV, prevent viruses from attaching to or entering host cells by blocking the receptors that viruses use to recognize and infect cells. This effectively makes the virus unable to "see" the cell, preventing infection.

Replication inhibitors often involve nucleic acid analogs, which mimic the building blocks of viral DNA or RNA but disrupt the replication process. These drugs target viral enzymes unique to viruses, such as viral DNA polymerase in herpes (targeted by acyclovir), reverse transcriptase in HIV (targeted by tenofovir), and RNA-dependent RNA polymerase in RNA viruses like SARS-CoV-2 (targeted by remdesivir). Because these enzymes are not found in human cells, they provide a selective target for antiviral therapy.

Assembly and exit inhibitors interfere with the virus's ability to assemble new viral particles or exit the host cell. Protease inhibitors, such as ritonavir and saquinavir used in HIV treatment, block viral proteases that cleave large viral polypeptides into functional proteins, resulting in nonfunctional viral particles. Neuraminidase inhibitors like oseltamivir (Tamiflu) and zanamivir target the influenza virus's neuraminidase enzyme, preventing newly formed viruses from leaving the infected cell and thereby reducing viral spread.

Another important antiviral strategy involves stimulating the host's immune response using interferons. Interferons are signaling proteins that enhance the production of antiviral proteins and activate immune defenses. Administering interferon alpha or drugs that induce interferon production can boost the body's natural ability to fight viral infections.

Understanding these mechanisms highlights the complexity of antiviral therapy and the importance of targeting specific viral processes to manage infections effectively. While most antivirals do not eradicate viruses completely, they play a crucial role in controlling viral diseases, especially chronic infections like HIV and hepatitis C, or acute infections in high-risk populations.

Protease inhibitors (e.g., Ritonavir & Saquinavir) inhibit what part of the viral infection process?

• A. They prevent viruses from binding to human cells by blocking their receptors.
• B. They inhibit DNA/RNA synthesis, preventing viruses from replicating.
• C. They block the large viral polypeptide from being cleaved into functional proteins.
• D. They are synthetic forms of interferons, which help activate the immune system.

Answer: (C)

Tenofovir is a drug used against HIV infections and work by inhibiting replication of the viral genome. Based only on that information, which of the following statements do you think is likely true?

• A. Tenofovir is likely a protease inhibitor.
• B. Tenofovir likely inhibits a viral specific DNA transcriptase.
• C. Tenofovir likely inhibits reverse transcriptase.
• D. Tenofovir likely inhibits RNA dependent RNA polymerase.

Answer: (C)

Here’s what students ask on this topic:

What are the main categories of antiviral drugs and how do they work?

Antiviral drugs are categorized based on the stage of the viral life cycle they target. The main categories include: 1) Entry inhibitors, which block the virus from attaching to or entering host cells by targeting cellular receptors; 2) Replication inhibitors, often nucleoside analogs, that disrupt viral DNA or RNA polymerases unique to viruses, preventing viral genome replication; 3) Assembly and exit inhibitors, such as protease inhibitors that prevent viral protein processing, and neuraminidase inhibitors that block virus release from infected cells; and 4) Immunity stimulators like interferons, which enhance the body's antiviral response by promoting antiviral protein production. These drugs reduce viral load and symptoms but usually do not cure infections, except in some cases like hepatitis C.

Why is selective toxicity challenging in developing antiviral drugs compared to antibiotics?

Selective toxicity is challenging in antiviral drug development because viruses replicate inside host cells and use the host's cellular machinery. Unlike bacteria targeted by antibiotics, viruses rely heavily on host enzymes and structures, making it difficult to target the virus without harming host cells. However, some viral enzymes, such as reverse transcriptase in HIV or viral DNA polymerase in herpes, are unique to viruses and serve as selective targets. This complexity means antiviral drugs often slow infection or reduce symptoms rather than completely curing the disease.

How do nucleoside analogs function as viral replication inhibitors?

Nucleoside analogs mimic the natural building blocks of viral DNA or RNA but differ slightly in structure. When incorporated into the viral genome during replication, they disrupt the process by causing premature termination or faulty viral nucleic acid synthesis. This inhibits the viral polymerases, such as reverse transcriptase in HIV or RNA-dependent RNA polymerase in RNA viruses like COVID-19. Since these enzymes are virus-specific and not found in human cells, nucleoside analogs provide selective inhibition of viral replication.

What role do protease inhibitors play in antiviral therapy?

Protease inhibitors block viral proteases, enzymes that cleave large viral polyproteins into functional smaller proteins necessary for assembling new virus particles. By inhibiting these proteases, the virus produces nonfunctional polyproteins, preventing proper viral assembly and maturation. This reduces the production of infectious viral particles. Examples include ritonavir and saquinavir used in HIV treatment. Protease inhibitors are crucial in controlling viral load and slowing disease progression.

How do interferons enhance the immune response against viral infections?

Interferons are signaling proteins produced by host cells in response to viral infections. Administered as antiviral drugs, interferons stimulate the immune system by promoting the production of antiviral proteins that inhibit viral replication and activate immune cells. They act as chemical messengers to alert neighboring cells and enhance the body's innate antiviral defenses. Interferon alpha is commonly used to boost immunity in chronic viral infections, helping to reduce viral load and symptoms.