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
