Chinese Scientists Identify Potent Influenza Inhibitor from Traditional Herbal Plant

Medical News: In a compelling new study, researchers from several major Chinese medical institutions have discovered that a natural compound derived from a traditional herbal medicine may hold powerful antiviral effects against influenza A virus. The compound, known as Atractylenolide III (or ACT-III), was found to directly bind to a critical influenza viral protein, effectively disrupting the virus's ability to hijack host cell functions and cause widespread lung inflammation.


Chinese Scientists Identify Potent Influenza Inhibitor from Traditional Herbal Plant

The study was conducted by scientists from the Department of Pharmacy at the Affiliated Guangdong Second Provincial General Hospital of Jinan University, the NMPA Key Laboratory for Research and Evaluation of Drug Metabolism at Southern Medical University, the State Key Laboratory of Organ Failure Research, and the Zhejiang Chinese Medical University. This Medical News report explores the breakthrough findings that show how ACT-III not only suppresses viral replication but also prevents dangerous immune overreactions that often lead to severe complications.
 
A New Hope Against Drug-Resistant Influenza
As influenza viruses continue to evolve and develop resistance to current treatments like oseltamivir and zanamivir, scientists are urgently searching for new antivirals that can overcome these challenges. One major target is a viral protein called Non-Structural Protein 1 (NS1), a known master regulator that helps the virus suppress the host's immune system and enhance its own replication.
 
The Chinese research team found that ACT-III, a natural compound extracted from the roots of the plant Atractylodes macrocephala, binds strongly to this NS1 protein. Using advanced molecular techniques like surface plasmon resonance and molecular docking analysis, they confirmed that ACT-III latches onto a key region of the NS1 protein - specifically at a site known as His169 - disrupting its function.
 
In lab tests using cultured lung cells and mouse models, ACT-III effectively reduced viral replication, eased flu-related symptoms, and protected lung tissue from severe damage.
 
Blocking Inflammation and Restoring Immune Balance
What makes ACT-III particularly promising is its ability to target both the virus and the body's immune response. When influenza A invades the body, it triggers a storm of inflammatory molecules that can worsen the illness, leading to complications like pneumonia or even death.
 
The researchers showed that ACT-III could tone down this immune overreaction by regulating a process known as macrophage polarization. Macrophages are frontline immune cells that can adopt different "modes" or types - one being pro-inflammatory (M1) and the other anti-inflammatory (M2). In the study, ACT-III helped shift the balance toward the M2 type, promoting healing and reducing tissue damage.
 
The study also revealed that ACT-III interfered with the interaction between NS1 and a host ce ll protein called CPSF4. This interaction normally allows the virus to manipulate how host cells process their RNA through a mechanism called alternative polyadenylation (APA), essentially helping the virus shut down normal immune responses. By disrupting this interaction, ACT-III helped restore normal immune function and blocked a key part of the virus’s strategy.
 
Strong Antiviral Effects in Mice
To test whether the compound works in living organisms, the researchers infected mice with a lethal dose of influenza A and treated them with ACT-III. The results were striking. Mice that received the compound showed less weight loss, had lower levels of viral RNA in their lungs, and experienced far less inflammation compared to untreated mice.
 
While oseltamivir (the current gold standard antiviral) was slightly more effective at reducing death rates, ACT-III held its own by offering a strong dual effect - reducing both virus levels and harmful inflammation.
 
Importantly, ACT-III showed no signs of toxicity in mice, even when administered for a week straight. This indicates it could be safe for further testing in humans.
 
Restoring Gene Regulation Hijacked by the Virus
One of the most unique and advanced aspects of this study was its focus on APA - a lesser-known but crucial process that determines how long the tails of messenger RNAs (mRNAs) are in human cells. Longer mRNA tails can change how genes are read, especially during infections.
 
Influenza's NS1 protein has been shown to shorten these mRNA tails through its interaction with CPSF4, leading to disrupted immune responses. ACT-III was able to reverse this effect. In particular, it restored the expression of IL-6, a key immune molecule whose levels are typically manipulated by influenza.
 
The compound's interference with NS1-CPSF4 binding was proven using co-immunoprecipitation assays, and researchers further confirmed that ACT-III’s ability to restore APA regulation correlated with reduced viral replication and enhanced immune protection.
 
A Potent Combination of Antiviral and Immune-Modulating Power
Taken together, the study positions ACT-III as a rare example of a compound that can directly attack the virus while also modulating the immune system to prevent collateral damage. It acts in a timely and specific way - blocking early-stage viral protein production and reducing overactive inflammation without suppressing critical defenses like interferon production.
 
Because influenza viruses mutate frequently and evade current drugs, having an agent like ACT-III that targets a highly conserved viral protein (NS1) provides a potential long-term solution. Moreover, its origin from a traditional medicinal plant makes it a compelling candidate for development into a safer, naturally derived antiviral therapy.
 
Conclusions
This groundbreaking study showcases ACT-III as a dual-function agent that not only binds to the influenza virus’s NS1 protein and disrupts its life cycle but also recalibrates the body’s immune response to prevent dangerous inflammation. It not only blocks viral replication by interfering with the NS1-CPSF4 interaction but also restores host gene regulation by correcting faulty RNA processing through alternative polyadenylation mechanisms. The compound was shown to suppress excessive inflammatory cytokines, promote healing macrophage types, and prevent tissue damage in both cell-based and animal models. Given its non-toxic profile and ability to target multiple disease pathways simultaneously, ACT-III could emerge as a key player in future flu treatment strategies. Researchers are now calling for additional trials, including clinical testing, to explore its potential for real-world application - possibly in combination with current antiviral medications to further enhance treatment efficacy. The findings add to a growing body of evidence that traditional medicinal compounds may hold untapped solutions to modern viral challenges.
 
The study findings were published in the peer reviewed journal: Phytomedicine.
https://www.sciencedirect.com/science/article/pii/S0944711325003447
 
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