Antiviral pharmacology and resistance mechanisms MCQs With Answer

Antiviral pharmacology and resistance mechanisms MCQs With Answer

Introduction: This question bank is designed for M.Pharm students studying Advanced Pharmacology-II who need a focused, high-yield review of antiviral agents and the molecular bases of resistance. The set covers mechanisms of action, prodrug activation, key viral targets (polymerases, proteases, entry/fusion proteins), clinically important resistance mutations, pharmacokinetic interactions and laboratory approaches to detect resistance. Each MCQ emphasizes conceptual understanding and clinical relevance, helping students reason about drug selection, cross-resistance patterns, and strategies to overcome or prevent resistance. Use these questions for self-assessment, exam preparation, and deeper study of antiviral therapeutics.

Q1. Which enzyme is primarily responsible for the initial phosphorylation (activation) of acyclovir in herpes simplex virus–infected cells?

  • Cellular thymidine kinase
  • Viral thymidine kinase
  • Viral DNA polymerase
  • Viral thymidylate synthase

Correct Answer: Viral thymidine kinase

Q2. The principal antiviral action of HIV protease inhibitors is to:

  • Block reverse transcription of viral RNA
  • Inhibit fusion of virus with host cell membrane
  • Prevent cleavage of Gag-Pol polyprotein, inhibiting maturation of virions
  • Inhibit viral integrase strand transfer

Correct Answer: Prevent cleavage of Gag-Pol polyprotein, inhibiting maturation of virions

Q3. Which neuraminidase mutation in influenza A (H1N1) is most commonly associated with high-level resistance to oseltamivir?

  • E119V
  • H275Y
  • R292K
  • S31N

Correct Answer: H275Y

Q4. The HIV reverse transcriptase mutation M184V primarily confers resistance to which drugs?

  • Zidovudine and stavudine
  • Efavirenz and nevirapine
  • Lamivudine and emtricitabine
  • Tenofovir and adefovir

Correct Answer: Lamivudine and emtricitabine

Q5. Sofosbuvir inhibits hepatitis C virus replication by acting as a:

  • NS3/4A protease inhibitor
  • NS5A replication complex inhibitor
  • Nucleotide analogue inhibitor of NS5B RNA-dependent RNA polymerase (chain terminator)
  • Host cyclophilin inhibitor

Correct Answer: Nucleotide analogue inhibitor of NS5B RNA-dependent RNA polymerase (chain terminator)

Q6. Between entecavir and tenofovir, which antiviral is generally considered to have the highest genetic barrier to resistance for chronic HBV therapy?

  • Entecavir
  • Lamivudine
  • Tenofovir
  • Adefovir

Correct Answer: Tenofovir

Q7. Cytomegalovirus resistance to ganciclovir due to impaired drug phosphorylation is most often caused by mutations in which viral gene?

  • UL97
  • UL54
  • US3
  • UL80

Correct Answer: UL97

Q8. Maraviroc exerts its anti-HIV effect by which mechanism?

  • Inhibiting reverse transcriptase
  • Binding to gp120 and blocking CD4 attachment
  • Antagonizing the CCR5 co-receptor on host cells to prevent viral entry
  • Inhibiting integrase strand transfer

Correct Answer: Antagonizing the CCR5 co-receptor on host cells to prevent viral entry

Q9. The widespread pre-existing resistance of influenza A to adamantanes (amantadine, rimantadine) is largely due to which M2 ion channel mutation?

  • H274Y
  • S31N
  • K103N
  • R292K

Correct Answer: S31N

Q10. Ritonavir is used as a pharmacoenhancer (booster) for other HIV protease inhibitors primarily because it:

  • Induces CYP3A4 to increase PI metabolism
  • Inhibits CYP3A4, reducing protease inhibitor metabolism and increasing plasma levels
  • Inhibits P-glycoprotein to increase renal clearance
  • Enhances viral protease binding to inhibitors

Correct Answer: Inhibits CYP3A4, reducing protease inhibitor metabolism and increasing plasma levels

Q11. NS5A inhibitors (e.g., daclatasvir) act primarily by:

  • Direct inhibition of the NS5B polymerase active site
  • Blocking proteolytic processing of HCV polyprotein
  • Disrupting NS5A-mediated assembly of replication complexes and virion assembly
  • Inhibiting host cell DNA synthesis

Correct Answer: Disrupting NS5A-mediated assembly of replication complexes and virion assembly

Q12. Which antiretroviral is a classic example of a nucleoside analogue that causes DNA chain termination due to modification at the 3′ position?

  • Zidovudine (AZT)
  • Nevirapine
  • Ritonavir
  • Maraviroc

Correct Answer: Zidovudine (AZT)

Q13. Which laboratory approach directly identifies known resistance-associated mutations in viral genes by sequencing?

  • Phenotypic susceptibility assay
  • Genotypic resistance testing
  • Virus culture plaque assay
  • Antigen capture ELISA

Correct Answer: Genotypic resistance testing

Q14. The HIV reverse transcriptase mutation K103N typically causes high-level resistance to which drug class?

  • Nucleoside reverse transcriptase inhibitors (NRTIs)
  • Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
  • Protease inhibitors
  • Integrase strand transfer inhibitors

Correct Answer: Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

Q15. Tenofovir alafenamide (TAF) differs from tenofovir disoproxil fumarate (TDF) mainly because TAF:

  • Is an active drug that does not require intracellular activation
  • Produces higher plasma tenofovir levels and lower intracellular drug concentration
  • Is a prodrug that achieves higher intracellular tenofovir diphosphate with lower plasma tenofovir exposure
  • Inhibits reverse transcriptase by noncompetitive binding

Correct Answer: Is a prodrug that achieves higher intracellular tenofovir diphosphate with lower plasma tenofovir exposure

Q16. One pharmacological reason why tenofovir alafenamide has a lower risk of renal toxicity compared with tenofovir disoproxil fumarate is:

  • Greater plasma tenofovir concentrations with TAF
  • Higher renal tubular uptake of TAF
  • Lower systemic/plasma tenofovir exposure with TAF while delivering more active drug intracellularly
  • Stronger CYP3A4 induction by TAF

Correct Answer: Lower systemic/plasma tenofovir exposure with TAF while delivering more active drug intracellularly

Q17. Neuraminidase inhibitors (oseltamivir, zanamivir) reduce influenza severity primarily by:

  • Preventing viral attachment to sialic acid receptors
  • Inhibiting viral uncoating in endosomes
  • Blocking viral neuraminidase, thereby inhibiting release of progeny virions from infected cells
  • Inhibiting viral RNA polymerase directly

Correct Answer: Blocking viral neuraminidase, thereby inhibiting release of progeny virions from infected cells

Q18. Raltegravir and dolutegravir inhibit HIV replication by targeting which enzymatic step?

  • Reverse transcriptase RNA-dependent DNA synthesis
  • Proteolytic cleavage of polyproteins
  • DNA strand transfer activity of integrase
  • Viral entry via CCR5 blocking

Correct Answer: DNA strand transfer activity of integrase

Q19. In viral evolution under drug pressure, compensatory mutations are best described as mutations that:

  • Directly increase the affinity of the drug to its target
  • Restore viral replicative fitness lost because of primary resistance mutations
  • Cause increased drug efflux from infected cells
  • Enable enzymatic inactivation of the antiviral compound

Correct Answer: Restore viral replicative fitness lost because of primary resistance mutations

Q20. Which class of direct-acting antivirals is represented by simeprevir and paritaprevir for hepatitis C virus?

  • NS5B nucleoside polymerase inhibitors
  • NS5A inhibitors
  • NS3/4A protease inhibitors
  • Host-targeting cyclophilin inhibitors

Correct Answer: NS3/4A protease inhibitors

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