USMLE STEP 1 PRACTICE QUESTION
Pharmacology mechanism of action
Today’s question was pulled from our massive library of questions in our USMLEDx assessment platform. It will test your understanding of commonly tested medications and their mechanisms of action. This second-order question requires you to identify the drug in question (based on the given general mechanism) and then choose its specific MOA. This question can be tricky, but it’s commonly tested—you need to know this one! Let’s see how you do; if you miss it, learn from the answer choices, explanation, and provided details. Good luck!
A 40-year-old man with chronic hepatitis B presents to his hepatologist for follow-up. Despite adherence to his current antiviral regimen, his viral load remains elevated, and liver function tests show persistent abnormalities. The hepatologist decides to initiate treatment with a medication known for its immunomodulatory effects. This medication binds to specific receptors on host cells, activating a signaling pathway that results in gene transcription that enhances the antiviral state. Which of the following best describes the medication's mechanism?
A. Activation of viral DNA replication by blocking reverse transcriptase activity
B. Inhibition of neuraminidase activity to prevent viral release from infected cells
C. Induction of host cell apoptosis by activating pro-apoptotic proteins
D. Activation of host cell immune response via JAK-STAT signaling pathway
E. Inhibition of viral entry into host cells by blocking viral fusion proteins
F. Activation of viral protease activity to prevent viral maturation
G. Inhibition of viral RNA replication by blocking RNA-dependent RNA polymerase
Detailed Breakdown of Answers + Correct Answer Below ⏬
ANSWER + QUESTION BREAKDOWN
The basic mental model for this week’s question comes from our detailed test-taking skills masterclass. Here’s how to think about this question for maximum efficiency and accuracy:
Step 1. Identify what the question wants (given in the last line); it wants you to find the drug’s MOA, which will be based on first identifying the drug (therefore, the goal is to identify the drug in question, then name its MOA).
Step 2. Read the vignette and find the drug in question.
Step 3. Name the drug and name its MOA (in your head, not from looking at the answer choices).
Step 4. Look to the answers in search of the exact MOA you stated to yourself from “Step 3” above.
GENERAL ANALYSIS
This question asks about the mechanism of action of a new drug introduced in the patient’s hepatitis B management. The vignette states that the medication binds to specific receptors on host cells, activating a signaling pathway that results in gene transcription that enhances the antiviral state. The drug being introduced in this scenario is interferon-alpha.
ANSWER CHOICES:
ANSWER CHOICE A: Activation of viral DNA replication by blocking reverse transcriptase activity
Reverse transcriptase is an enzyme used by retroviruses, such as HIV, to replicate their RNA into DNA. Blocking this enzyme would inhibit viral replication. Interferon alpha does not block reverse transcriptase; it acts on the host's immune system rather than directly on viral enzymes.
ANSWER CHOICE B: Inhibition of neuraminidase activity to prevent viral release from infected cells
Neuraminidase is an enzyme found in influenza viruses that helps release new viral particles from infected cells. Interferon alpha does not inhibit neuraminidase; this mechanism is specific to neuraminidase inhibitors like oseltamivir.
ANSWER CHOICE C: Induction of host cell apoptosis by activating pro-apoptotic proteins
Apoptosis is the process of programmed cell death, which can be induced by specific signals within the cell. While interferon alpha can influence apoptosis, its primary mechanism is not through direct induction of apoptosis via pro-apoptotic proteins.
ANSWER CHOICE D: Activation of host cell immune response via JAK-STAT signaling pathway
Interferon alpha binds to type I interferon receptors, activating the JAK-STAT pathway, which leads to the transcription of genes that enhance the antiviral state and modulate the immune response. This is the primary mechanism of action of interferon alpha.
ANSWER CHOICE E: Inhibition of viral entry into host cells by blocking viral fusion proteins
Blocking viral fusion proteins would prevent viruses from entering host cells. Interferon alpha does not block viral entry; it acts after the virus has entered the host cells by enhancing the immune response.
ANSWER CHOICE F: Activation of viral protease activity to prevent viral maturation
Viral proteases are enzymes that process viral proteins necessary for maturation. Interferon alpha does not activate viral proteases; it acts on the host's immune system rather than directly on viral maturation processes.
ANSWER CHOICE G: Inhibition of viral RNA replication by blocking RNA-dependent RNA polymerase
RNA-dependent RNA polymerase is an enzyme used by RNA viruses to replicate their RNA genomes. Interferon alpha does not directly inhibit viral RNA polymerase; its action is more focused on modulating the host immune response.
FINAL VERDICT…
Interferon alpha is a cytokine that plays a crucial role in the immune response to viral infections. It binds to type I interferon receptors (IFNAR1 and IFNAR2) on host cells, activating the JAK-STAT signaling pathway. This pathway involves the phosphorylation of Janus kinases (JAK1 and Tyk2) and subsequent phosphorylation of STAT proteins (STAT1 and STAT2). These phosphorylated STATs dimerize and translocate to the nucleus, where they activate the transcription of interferon-stimulated genes (ISGs). These genes encode proteins that establish an antiviral state within the cell, enhance antigen presentation, and modulate various immune functions, thereby helping to control viral infections.
CORRECT ANSWER: D) Activation of host cell immune response via JAK-STAT signaling pathway
