MCQ Quiz: Antivirals

Welcome, PharmD students, to this MCQ quiz on Antivirals! Treating viral infections presents unique challenges due to the intimate relationship between viruses and host cells. This quiz will test your understanding of the pharmacology, medicinal chemistry, and therapeutic principles of various antiviral drug classes used to combat infections caused by herpesviruses, influenza, HIV, hepatitis viruses, and others. We will explore their mechanisms of action, viral targets, resistance mechanisms, and key clinical considerations. Let’s dive into the world of antiviral pharmacotherapy!

1. A primary challenge in developing selective antiviral drugs is that viruses:

• a) Have their own extensive metabolic machinery separate from the host.
• b) Are easily killed by common antibiotics.
• c) Utilize host cell machinery for replication, making it difficult to target viral processes without harming the host cell.
• d) Are prokaryotic organisms.

Answer: c) Utilize host cell machinery for replication, making it difficult to target viral processes without harming the host cell.

2. Acyclovir, an anti-herpesvirus agent, is a nucleoside analog that requires phosphorylation to its active triphosphate form. The initial phosphorylation step is selectively catalyzed by:

• a) Host cell mitochondrial kinase.
• b) Viral-encoded thymidine kinase (TK).
• c) Host cell cytoplasmic kinase.
• d) Reverse transcriptase.

Answer: b) Viral-encoded thymidine kinase (TK).

3. The mechanism of action of acyclovir triphosphate involves:

• a) Inhibition of viral neuraminidase.
• b) Inhibition of viral DNA polymerase and incorporation into viral DNA causing chain termination.
• c) Blocking viral entry into host cells.
• d) Inhibiting viral protease.

Answer: b) Inhibition of viral DNA polymerase and incorporation into viral DNA causing chain termination.

4. Valacyclovir is a prodrug of acyclovir. The primary advantage of using valacyclovir is its:

• a) Broader antiviral spectrum.
• b) Different mechanism of action.
• c) Improved oral bioavailability compared to acyclovir.
• d) Reduced need for viral thymidine kinase activation.

Answer: c) Improved oral bioavailability compared to acyclovir.

5. Oseltamivir (Tamiflu) and zanamivir (Relenza) are anti-influenza drugs that belong to which class?

• a) M2 protein inhibitors
• b) Neuraminidase inhibitors
• c) DNA polymerase inhibitors
• d) Reverse transcriptase inhibitors

Answer: b) Neuraminidase inhibitors

6. The mechanism of action of neuraminidase inhibitors in treating influenza involves:

• a) Preventing viral attachment to host cells.
• b) Blocking the uncoating of the virus within the host cell.
• c) Inhibiting viral RNA replication.
• d) Preventing the release of newly formed viral particles from infected host cells.

Answer: d) Preventing the release of newly formed viral particles from infected host cells.

7. Baloxavir marboxil is an anti-influenza agent with a distinct mechanism of action, which is:

• a) Inhibition of neuraminidase.
• b) Inhibition of the cap-dependent endonuclease activity of the viral polymerase, interfering with viral mRNA synthesis.
• c) Blocking the M2 ion channel.
• d) Inhibition of viral DNA synthesis.

Answer: b) Inhibition of the cap-dependent endonuclease activity of the viral polymerase, interfering with viral mRNA synthesis.

8. Ganciclovir is an antiviral agent primarily used for the treatment of infections caused by which herpesvirus?

• a) Herpes Simplex Virus (HSV) only.
• b) Varicella-Zoster Virus (VZV) only.
• c) Cytomegalovirus (CMV).
• d) Epstein-Barr Virus (EBV) only.

Answer: c) Cytomegalovirus (CMV).

9. Foscarnet is an antiviral agent that inhibits viral DNA polymerase and reverse transcriptase. Unlike nucleoside analogs, it:

• a) Requires intracellular phosphorylation by viral kinases.
• b) Does not require phosphorylation for activity (it’s a pyrophosphate analog).
• c) Is only active against influenza viruses.
• d) Is only administered orally.

Answer: b) Does not require phosphorylation for activity (it’s a pyrophosphate analog).

10. Which of the following is a major class of antiretroviral drugs used in the treatment of HIV infection that targets the enzyme responsible for converting viral RNA into DNA?

• a) Protease Inhibitors (PIs)
• b) Nucleos(t)ide Reverse Transcriptase Inhibitors (NRTIs) and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
• c) Integrase Strand Transfer Inhibitors (INSTIs)
• d) Fusion Inhibitors

Answer: b) Nucleos(t)ide Reverse Transcriptase Inhibitors (NRTIs) and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

11. HIV Protease Inhibitors (PIs) work by:

• a) Preventing the virus from entering host CD4+ cells.
• b) Inhibiting the viral enzyme responsible for cleaving viral polyproteins into mature, functional proteins.
• c) Blocking the integration of viral DNA into the host genome.
• d) Inhibiting reverse transcriptase.

Answer: b) Inhibiting the viral enzyme responsible for cleaving viral polyproteins into mature, functional proteins.

12. Integrase Strand Transfer Inhibitors (INSTIs) are antiretroviral drugs that target which step of the HIV replication cycle?

• a) Viral attachment and entry.
• b) Reverse transcription of viral RNA.
• c) Integration of viral DNA into the host cell’s DNA.
• d) Maturation of new viral particles.

Answer: c) Integration of viral DNA into the host cell’s DNA.

13. The principle of Highly Active Antiretroviral Therapy (HAART) or combination antiretroviral therapy (cART) for HIV infection involves:

• a) Using a single potent antiviral drug.
• b) Using multiple antiretroviral drugs from different classes simultaneously to suppress viral replication, reduce resistance development, and improve immune function.
• c) Intermittent therapy with short courses of antivirals.
• d) Focusing only on boosting the host immune system without targeting the virus.

Answer: b) Using multiple antiretroviral drugs from different classes simultaneously to suppress viral replication, reduce resistance development, and improve immune function.

14. Tenofovir and entecavir are nucleos(t)ide analogs commonly used for the treatment of chronic:

• a) Herpes Simplex Virus (HSV) infection.
• b) Influenza A.
• c) Hepatitis B Virus (HBV) infection.
• d) Cytomegalovirus (CMV) retinitis.

Answer: c) Hepatitis B Virus (HBV) infection.

15. Direct-Acting Antivirals (DAAs) have revolutionized the treatment of Hepatitis C Virus (HCV) infection. These agents typically target specific HCV non-structural proteins such as:

• a) Hemagglutinin and Neuraminidase.
• b) NS3/4A protease, NS5B polymerase, and NS5A protein.
• c) Reverse transcriptase and integrase.
• d) DNA polymerase and thymidine kinase.

Answer: b) NS3/4A protease, NS5B polymerase, and NS5A protein.

16. From a medicinal chemistry perspective, many nucleoside analog antivirals (e.g., acyclovir, zidovudine) act as chain terminators during viral nucleic acid synthesis because they often lack:

• a) A phosphate group.
• b) A nitrogenous base.
• c) A 3′-hydroxyl group on the sugar moiety (or have a modification that prevents further elongation).
• d) A 5′-hydroxyl group.

Answer: c) A 3′-hydroxyl group on the sugar moiety (or have a modification that prevents further elongation).

17. Resistance to acyclovir in HSV or VZV can occur due to mutations in the viral:

• a) Neuraminidase gene.
• b) Thymidine kinase gene or DNA polymerase gene.
• c) Protease gene.
• d) M2 protein gene.

Answer: b) Thymidine kinase gene or DNA polymerase gene.

18. Which of the following is a common pharmacological goal of antiviral therapy for chronic viral infections like HIV or HBV?

• a) Complete eradication of the virus within a short treatment course.
• b) Long-term suppression of viral replication to prevent disease progression and transmission.
• c) Stimulation of viral replication to enhance immunity.
• d) Treatment of symptoms only, without affecting viral load.

Answer: b) Long-term suppression of viral replication to prevent disease progression and transmission.

19. The adamantanes (amantadine and rimantadine) were previously used for influenza A but are no longer recommended due to:

• a) Severe nephrotoxicity.
• b) Widespread resistance.
• c) Lack of oral bioavailability.
• d) Their very narrow spectrum covering only influenza B.

Answer: b) Widespread resistance.

20. A key principle in the pharmacology of many antivirals is that they are most effective when:

• a) Administered late in the course of infection after peak viral replication.
• b) Viral replication is actively occurring, and often when initiated early in the infection.
• c) The host immune system is completely suppressed.
• d) Used as monotherapy for chronic infections like HIV.

Answer: b) Viral replication is actively occurring, and often when initiated early in the infection.

21. “Ribavirin” is a broad-spectrum antiviral agent whose uses include combination therapy for Hepatitis C (historically) and treatment of severe Respiratory Syncytial Virus (RSV) infection. Its mechanism is complex but involves:

• a) Inhibition of neuraminidase.
• b) Interference with viral RNA metabolism and synthesis through multiple mechanisms.
• c) Direct inhibition of viral DNA polymerase.
• d) Blocking the M2 ion channel.

Answer: b) Interference with viral RNA metabolism and synthesis through multiple mechanisms.

22. What is a common adverse effect of many NRTIs used in HIV therapy, related to mitochondrial toxicity?

• a) Severe hypertension.
• b) Lactic acidosis and hepatic steatosis.
• c) Hair growth.
• d) Enhanced renal function.

Answer: b) Lactic acidosis and hepatic steatosis.

23. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) like efavirenz or nevirapine differ from NRTIs in that they:

• a) Also inhibit viral protease.
• b) Bind to a different, allosteric site on the reverse transcriptase enzyme, directly inhibiting its activity.
• c) Require intracellular phosphorylation to become active.
• d) Are only effective against DNA viruses.

Answer: b) Bind to a different, allosteric site on the reverse transcriptase enzyme, directly inhibiting its activity.

24. One of the challenges in anti-HIV therapy is the virus’s high mutation rate, which contributes significantly to:

• a) Its inability to infect CD4+ cells.
• b) The rapid development of drug resistance if therapy is suboptimal.
• c) Its slow replication cycle.
• d) The ease of developing a curative vaccine.

Answer: b) The rapid development of drug resistance if therapy is suboptimal.

25. Interferon-alfa was historically used in the treatment of chronic Hepatitis B and C. Its antiviral effect is primarily mediated by:

• a) Direct inhibition of viral polymerase.
• b) Induction of an antiviral state in host cells and modulation of the host immune response.
• c) Blocking viral entry.
• d) Inhibiting viral protease.

Answer: b) Induction of an antiviral state in host cells and modulation of the host immune response.

26. From a medicinal chemistry standpoint, the conversion of ganciclovir to valganciclovir (its L-valyl ester prodrug) was designed to:

• a) Decrease its antiviral potency.
• b) Increase its oral bioavailability.
• c) Make it effective against influenza.
• d) Reduce its selectivity for CMV.

Answer: b) Increase its oral bioavailability.

27. Cidofovir is a nucleotide analog effective against CMV that, unlike ganciclovir, does not require initial phosphorylation by viral kinases because it:

• a) Is already a monophosphate analog (nucleotide).
• b) Directly inhibits viral release.
• c) Blocks viral attachment.
• d) Is a non-competitive inhibitor of DNA polymerase.

Answer: a) Is already a monophosphate analog (nucleotide).

28. A significant dose-limiting toxicity of cidofovir is:

• a) Bone marrow suppression.
• b) Nephrotoxicity, often co-administered with probenecid to reduce this risk.
• c) Severe rash.
• d) Cardiotoxicity.

Answer: b) Nephrotoxicity, often co-administered with probenecid to reduce this risk.

29. Maraviroc is an antiretroviral drug that acts as a CCR5 antagonist. Its mechanism involves:

• a) Inhibiting reverse transcriptase.
• b) Blocking the binding of HIV gp120 to the CCR5 co-receptor, thus preventing viral entry into susceptible host cells.
• c) Inhibiting HIV protease.
• d) Preventing integration of viral DNA.

Answer: b) Blocking the binding of HIV gp120 to the CCR5 co-receptor, thus preventing viral entry into susceptible host cells. (Requires tropism testing).

30. The development of antiviral resistance is a major concern. Resistance typically arises from:

• a) Enhanced host immune response.
• b) Mutations in viral genes encoding the drug target (e.g., polymerase, protease) or proteins involved in drug activation.
• c) Decreased oral bioavailability of the drug.
• d) Increased plasma protein binding of the drug.

Answer: b) Mutations in viral genes encoding the drug target (e.g., polymerase, protease) or proteins involved in drug activation.

31. Sofosbuvir is a cornerstone DAA for HCV treatment. It is a nucleotide analog that inhibits:

• a) HCV NS3/4A protease.
• b) HCV NS5B RNA-dependent RNA polymerase.
• c) HCV NS5A protein.
• d) Viral entry.

Answer: b) HCV NS5B RNA-dependent RNA polymerase.

32. Many antiviral agents, particularly those for HIV and Hepatitis, are prone to significant drug-drug interactions, often involving:

• a) Only chelation with divalent cations.
• b) Competition for renal tubular secretion.
• c) Induction or inhibition of cytochrome P450 enzymes or drug transporters like P-glycoprotein.
• d) Alteration of gastric pH only.

Answer: c) Induction or inhibition of cytochrome P450 enzymes or drug transporters like P-glycoprotein.

33. The “pharmacophore” for a class of antiviral drugs (e.g., neuraminidase inhibitors) refers to:

• a) The specific viral species they target.
• b) The essential structural features and their arrangement required for binding to the viral target and eliciting a biological effect.
• c) The typical adverse effect profile.
• d) The route of administration.

Answer: b) The essential structural features and their arrangement required for binding to the viral target and eliciting a biological effect.

34. A key therapeutic principle in using anti-influenza agents like oseltamivir is that they are most effective when initiated:

• a) 5-7 days after symptom onset.
• b) As early as possible, typically within 48 hours of symptom onset.
• c) Only for prophylaxis, not treatment.
• d) After the patient has fully recovered to prevent recurrence.

Answer: b) As early as possible, typically within 48 hours of symptom onset.

35. The term “virostatic” would best describe an antiviral agent that:

• a) Directly kills virus particles.
• b) Irreversibly damages the host cell.
• c) Inhibits viral replication without necessarily eliminating all latent or integrated virus.
• d) Is used to sterilize equipment.

Answer: c) Inhibits viral replication without necessarily eliminating all latent or integrated virus.

36. From a medicinal chemistry perspective, achieving selectivity for viral enzymes over host enzymes is a major goal in antiviral drug design because:

• a) It makes the drug cheaper to synthesize.
• b) It minimizes toxicity to the host cells by specifically targeting viral components.
• c) It guarantees oral bioavailability.
• d) It ensures a very broad spectrum of activity.

Answer: b) It minimizes toxicity to the host cells by specifically targeting viral components.

37. The “viral target site” for an antiviral drug is:

• a) The patient’s immune system.
• b) A specific molecule or process in the virus or virus-infected cell that is essential for viral replication or pathogenesis.
• c) The hospital pharmacy.
• d) The drug’s metabolic pathway.

Answer: b) A specific molecule or process in the virus or virus-infected cell that is essential for viral replication or pathogenesis.

38. Which class of anti-HIV drugs often has a high pill burden and significant drug interaction potential due to CYP3A4 inhibition (requiring “boosting” with ritonavir or cobicistat for some agents)?

• a) NRTIs
• b) NNRTIs
• c) Protease Inhibitors (PIs)
• d) INSTIs

Answer: c) Protease Inhibitors (PIs)

39. Herpesviruses establish latency. Antiviral agents like acyclovir are effective against _______ but do not eradicate the _______.

• a) latent virus; replicating virus
• b) replicating virus; latent virus
• c) bacterial co-infections; viral infection
• d) fungal infections; viral latency

Answer: b) replicating virus; latent virus

40. The medicinal chemistry strategy of creating “fixed-dose combinations” (FDCs) of multiple antiretrovirals in a single pill aims to:

• a) Increase the risk of drug interactions.
• b) Improve patient adherence, simplify regimens, and potentially enhance efficacy or reduce resistance development.
• c) Make the medication more expensive.
• d) Only be used for short-term therapy.

Answer: b) Improve patient adherence, simplify regimens, and potentially enhance efficacy or reduce resistance development.

41. Which influenza type is primarily responsible for seasonal epidemics and has the potential for pandemics due to antigenic shift?

• a) Influenza C
• b) Influenza B
• c) Influenza A
• d) Influenza D

Answer: c) Influenza A

42. A common counseling point for patients starting antiviral therapy for herpes zoster (shingles) is that early treatment can:

• a) Eradicate the VZV virus completely from the body.
• b) Reduce the severity and duration of acute pain and potentially reduce the risk or duration of postherpetic neuralgia.
• c) Prevent chickenpox in their contacts.
• d) Make them immune to future VZV reactivations.

Answer: b) Reduce the severity and duration of acute pain and potentially reduce the risk or duration of postherpetic neuralgia.

43. Medicinal chemistry efforts for antivirals often focus on improving:

• a) Only the color of the drug.
• b) Target specificity, oral bioavailability, pharmacokinetic profile (e.g., half-life), and resistance profile.
• c) The complexity of the synthesis.
• d) The taste of the inactive ingredients.

Answer: b) Target specificity, oral bioavailability, pharmacokinetic profile (e.g., half-life), and resistance profile.

44. The pharmacology of antiviral drugs often involves targeting processes unique to viral replication, such as:

• a) Host cell glycolysis.
• b) Viral attachment/entry, viral genome replication (e.g., specific polymerases), viral protein processing (e.g., proteases), or viral release.
• c) Host cell mitosis.
• d) Bacterial cell wall synthesis.

Answer: b) Viral attachment/entry, viral genome replication (e.g., specific polymerases), viral protein processing (e.g., proteases), or viral release.

45. For chronic hepatitis B, the goal of antiviral therapy with agents like tenofovir or entecavir is generally to:

• a) Achieve rapid eradication of HBV within a few weeks.
• b) Suppress HBV DNA to undetectable levels, normalize liver enzymes, and prevent progression to cirrhosis or hepatocellular carcinoma.
• c) Only treat acute symptoms.
• d) Prevent transmission to others without affecting the patient’s viral load.

Answer: b) Suppress HBV DNA to undetectable levels, normalize liver enzymes, and prevent progression to cirrhosis or hepatocellular carcinoma.

46. Which of the following is an important consideration from a pharmacology perspective when selecting an antiviral agent?

• a) The patient’s preferred brand.
• b) The specific virus causing the infection and its likely susceptibility to the agent.
• c) The cost of the medication as the sole factor.
• d) The availability of the drug in a brightly colored tablet.

Answer: b) The specific virus causing the infection and its likely susceptibility to the agent.

47. From a medicinal chemistry perspective, “isosteric replacement” in drug design involves:

• a) Replacing a functional group with another group of similar size, shape, and electronic properties to modify activity or PK.
• b) Adding a large lipid chain to increase water solubility.
• c) Removing all functional groups.
• d) Converting an oral drug to an injectable one.

Answer: a) Replacing a functional group with another group of similar size, shape, and electronic properties to modify activity or PK. (This is a general med-chem principle applicable to antivirals).

48. The “therapeutic window” for antiviral drugs can be narrow for some agents, meaning:

• a) They are effective against a very wide range of viruses.
• b) The concentration range that provides efficacy without significant toxicity is small, requiring careful dosing and monitoring.
• c) They can only be used for a short period.
• d) They are always safe at any dose.

Answer: b) The concentration range that provides efficacy without significant toxicity is small, requiring careful dosing and monitoring.

49. Drug interactions involving antiviral agents are common. For example, many HIV protease inhibitors are potent inhibitors of:

• a) Renal tubular secretion.
• b) CYP3A4, leading to interactions with other CYP3A4 substrates.
• c) Glucuronidation.
• d) P-glycoprotein only.

Answer: b) CYP3A4, leading to interactions with other CYP3A4 substrates.

50. The pharmacist’s role in antiviral pharmacotherapy involves understanding the pharmacology and medicinal chemistry of these agents to:

• a) Synthesize new antiviral compounds.
• b) Optimize patient care by ensuring appropriate drug selection, dosing, monitoring for efficacy and adverse effects, managing interactions, and counseling on adherence.
• c) Only dispense the medications as prescribed without further input.
• d) Diagnose viral infections using laboratory tests.

Answer: b) Optimize patient care by ensuring appropriate drug selection, dosing, monitoring for efficacy and adverse effects, managing interactions, and counseling on adherence.