Evidence mapPaperPMID 42568525Full record

ReviewFrontiers in cellular and infection microbiology2026

From neuraminidase inhibitors to novel mechanisms: expanding therapeutic strategies against influenza.

Yan Sun, Puongtip Kunanusorn, Kuang Ming Tup, Santosh Chokkakula, Bing Yang

Abstract readReview
In one paragraph

Review in Frontiers in cellular and infection microbiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Yan SunDepartment of Public Health, International School, Krirk University, Bangkok, Thailand.
Puongtip KunanusornDepartment of Medical and Nursing Science, International College, Krirk University, Bangkok, Thailand.
Kuang Ming TupDepartment of Medical and Nursing Science, International College, Krirk University, Bangkok, Thailand.
Santosh ChokkakulaDepartment of Microbiology, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju, Republic of Korea.
Bing YangDepartment of Public Health, International School, Krirk University, Bangkok, Thailand.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Seasonal influenza causes approximately one billion infections and up to 650,000 respiratory deaths annually. Despite decades of antiviral development, the therapeutic arsenal remains constrained by time-dependent efficacy (clinical benefit confined largely to treatment initiated within 48 hours of symptom onset), low genetic resistance barriers (resistance arising from a single point mutation), and critical evidence gaps in high-risk populations. This review critically evaluates the antiviral landscape, focusing on next-generation cap-dependent endonuclease inhibitors (CENIs), resistance implications across all approved drug classes, translational barriers in host-directed therapies and biologics, and H5N1 pandemic preparedness. Suraxavir marboxil, ZX-7101A, and the first approved polymerase basic protein 2 (PB2) inhibitor, onradivir, confirm that scaffold-level optimization (incremental structural refinement within an existing drug class) can meaningfully reduce resistance emergence rates. Across all approved classes, a shared failure pattern is evident: single-target dependence, low-fitness-cost resistance mutations (mutations that confer drug resistance without measurably impairing viral replication or transmission), and a therapeutic window that most patients do not reach. Combination antiviral therapy shows promise for resistance prevention, though the FLAGSTONE Phase 3 trial demonstrated that virological benefit does not consistently translate to clinical outcomes in hospitalized patients. Host-directed therapies and biologics face a shared translational obstacle: the biological window of maximal activity consistently precedes the clinical window of patient presentation, and systemic biologics cannot achieve inhibitory concentrations at the respiratory mucosal surface. For H5N1, preparedness relies on a single observationally supported drug class; baloxavir is absent from most national stockpiles, and no randomized trial data exists for any antiviral in human H5N1 infection. Adaptive trial infrastructure, diversified stockpiling to include next-generation CENIs, and equitable global antiviral access are the most urgent priorities in influenza therapeutics.

Indexed as

Antiviral AgentsEnzyme InhibitorsInfluenza, HumanNeuraminidaseAnimalsDrug Resistance, ViralHumansInfluenza A Virus, H5N1 SubtypeAntiviral AgentsEnzyme InhibitorsNeuraminidaseantiviral resistanceantiviral therapycap-dependent endonuclease inhibitorH5N1host-directed therapyinfluenza virusneuraminidase inhibitorsnovel antiviral agents

Identifiers

PMID42568525
PMCPMC13447180

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.