Doravirine

證據等級: L5

預測適應症: 3 個

Doravirine: From HIV-1 Infection to Feline Acquired Immunodeficiency Syndrome

One-Sentence Summary

Doravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) whose established use, based on the mechanistic notes in this evidence pack, is treatment of HIV-1 infection. The TxGNN model’s top-ranked prediction for this drug is feline acquired immunodeficiency syndrome (FIV) — a veterinary, non-human indication — with no clinical trials and no literature currently supporting this specific link, and the evidence pack itself flags the underlying mechanism as unlikely to translate across species/viruses.

Quick Overview

Item	Content
Original Indication	HIV-1 infection (NNRTI; inferred from the repurposing rationale notes — not present as structured data, since `original_indications` and `licenses` are both empty)
Predicted New Indication	Feline acquired immunodeficiency syndrome (FIV)
TxGNN Prediction Score	99.93%
Evidence Level	L5
US Market Status	Not Marketed (未上市)
Number of NDAs	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

Detailed mechanism-of-action data is marked as a data gap in this evidence pack (original_moa: [Data Gap]). Based on the mechanistic notes attached to the predicted indications, Doravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) whose proven efficacy is in human HIV-1 infection, acting by binding an allosteric pocket on the HIV-1 reverse transcriptase enzyme.

FIV (feline immunodeficiency virus) belongs to the same Lentivirus genus as HIV-1, and TxGNN’s knowledge graph likely surfaced this candidate through a shared category association (“reverse transcriptase inhibitor” ↔ “lentiviral infection”) rather than direct experimental evidence. However, the evidence pack’s own mechanistic-link note is explicit that this analogy is weak: NNRTI binding pockets are highly virus/species-specific, and Doravirine — like other NNRTIs — is not known to inhibit reverse transcriptases from lentiviruses other than HIV-1. FIV is also a veterinary disease, which falls outside the standard human-drug repurposing pathway entirely.

For reference, the second-ranked prediction (simian immunodeficiency virus infection) carries a similarly high TxGNN score and is supported by one indirect review-level publication — but that publication discusses islatravir (a translocation inhibitor, mechanistically distinct from Doravirine’s NNRTI action), not Doravirine itself. The third-ranked prediction (a rare neurodevelopmental disorder) has no plausible mechanistic link at all and is flagged in the source data as a likely embedding-proximity artifact. Taken together, the top three TxGNN predictions for this drug do not currently constitute an actionable human repurposing signal.

Clinical Trial Evidence

Currently no related clinical trials registered

Literature Evidence

Currently no related literature available

(Note: one review-level publication, PMID 31658118, was found for the related rank-2 prediction — simian immunodeficiency virus infection — but it discusses islatravir, not Doravirine, and does not support the FIV indication above.)

US Market Information

No marketing authorizations are on record for this drug. Market status: Not Marketed (0 licenses).

Safety Considerations

Please refer to the package insert for safety information.

(Note: safety.key_warnings, safety.contraindications, and DDI query results are all empty/not found in this evidence pack. This corresponds to data gap DG001 — TFDA label warnings/contraindications — flagged as Blocking severity, meaning this candidate cannot proceed to the S1 safety pre-screening stage until resolved.)

Conclusion and Next Steps

Decision: Hold

Rationale:

Evidence level is L5 (model prediction only) with zero clinical trials and zero literature directly supporting Doravirine for FIV, the top-ranked disease is a veterinary indication outside standard human drug development, and the mechanistic rationale attached to this prediction itself assesses the cross-species/cross-virus extrapolation as biologically weak.
A Blocking-severity data gap (DG001 — TFDA warnings/contraindications) independently prevents this candidate from entering the S1 safety pre-screening stage regardless of efficacy evidence.

To proceed, the following is needed:

TFDA label data (warnings, contraindications) to resolve DG001 and enable S1 safety screening
Confirmed mechanism-of-action data via DrugBank API to resolve DG002 and support a rigorous mechanistic-link analysis
Direct experimental or clinical evidence of Doravirine activity against non-HIV-1 lentiviral reverse transcriptases, if this indication is to be pursued further
Re-evaluation of whether TxGNN’s top-ranked candidates for this drug reflect a genuine repurposing signal or a knowledge-graph category artifact, given all three top predictions currently lack direct supporting evidence
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.