LAT9997, a 6-amino acid linear peptide derived from human growth hormone, significantly improved survival in severe influenza by reducing viral load, lung inflammation, and tissue damage in mice.
Effective after symptom onsetUnlike most flu drugs that only work early, LAT9997 significantly improved disease severity even when treatment began after severe influenza symptoms appeared in mice
What the researchers found
Intranasal LAT9997 (6-amino acid growth hormone fragment) significantly improved survival in severe murine influenza by reducing viral burden, cytokine storm, neutrophil infiltration, vascular leak, and epithelial cell death while preserving protective alveolar macrophages, even when initiated after symptom onset.
Why it matters
Current flu treatments (like Tamiflu) only work if given very early. A treatment that works after severe disease develops — by calming the immune overreaction rather than just fighting the virus — could save lives during flu pandemics and severe seasonal outbreaks. Using a natural human peptide fragment reduces the risk of off-target effects.
The numbers in context
LAT9997 is 6 amino acids (versus 16 in the parent compound LAT8881) and is linear rather than cyclic, making it easier to produce.
How the study worked
Mice were infected with influenza virus to model severe disease. LAT8881 (16 aa cyclic) and LAT9997 (6 aa linear fragment) were administered intranasally from day 1 post-infection or after symptom onset. Outcomes: survival, lung pathology, damage markers, vascular leak, epithelial death, viral load, cytokines, immune cell infiltration. Structure-activity relationship studied by sequential amino acid trimming.
Who was studied
Influenza-infected animal models
What this study cannot tell us
Preclinical mouse model only — mouse and human immune responses to influenza differ significantly. Intranasal delivery may be challenging in severely ill patients who are intubated. The relationship between this growth hormone fragment and growth hormone receptor signaling needs clarification. Manufacturing and stability of the peptide for clinical use not addressed.
How to read the evidence
Preliminary evidence from a well-designed preclinical study with dose-response data, structure-activity relationships, and multiple mechanistic endpoints. Translation to human influenza treatment remains unproven.
When this study was published
Published in 2024, representing a novel host-directed therapeutic approach for severe influenza at the preclinical stage.
The bigger picture
The biggest killer in severe flu isn't the virus itself — it's the body's own immune overreaction (cytokine storm). Most antiviral drugs target the virus but do nothing about the inflammatory damage. This peptide takes the opposite approach: it calms the immune overreaction while also reducing viral load, hitting severe influenza from both angles. If it works in humans, it could fill the critical gap in treatment options for patients already severely ill with influenza.
Questions still open
- Does LAT9997 work against different influenza strains and subtypes, including avian influenza?
- Could this peptide be effective against other respiratory viruses that cause hyperinflammation, like COVID-19?
- What is the mechanism by which a growth hormone fragment reduces both viral load and inflammation simultaneously?
Common questions
How can a piece of growth hormone fight the flu?
Why is treating severe flu after symptoms appear so difficult?
Read the original research
Harnessing Endogenous Peptide Compounds as Potential Therapeutics for Severe Influenza.
The Journal of infectious diseases, 230(2), e384-e394
Citation
West, Alison C; Harpur, Christopher M; Le Page, Mélanie A; Lam, Maggie; Hodges, Christopher; Ely, Lauren K; Gearing, Andrew J; Tate, Michelle D. (2024). Harnessing Endogenous Peptide Compounds as Potential Therapeutics for Severe Influenza.. The Journal of infectious diseases, 230(2), e384-e394. https://doi.org/10.1093/infdis/jiad566