Molecular docking of potential inhibitors for influenza H7N9
Zekun Liu1, Junpeng Zhao1, Weichen Li1
1Medical College, Hunan Normal University, Changsha, Hunan 410013, China.
Abstract:
As a new strain of virus emerged in 2013, avian influenza A (H7N9) virus is a threat to the public health, due to its high lethality and pathogenicity. Furthermore, H7N9 has already generated various mutations such as neuraminidase R294K mutation which could make the anti-influenza oseltamivir less effective or ineffective. In this regard, it is urgent to develop new effective anti-H7N9 drug. In this study, we used the general H7N9 neuraminidase and oseltamivir-resistant influenza virus neuraminidase as the acceptors and employed the small molecules including quercetin, chlorogenic acid, baicalein, and oleanolic acid as the donors to perform the molecular docking for exploring the binding abilities between these small molecules and neuraminidase. The results showed that quercetin, chlorogenic acid, oleanolic acid, and baicalein present oseltamivir-comparable high binding potentials with neuraminidase. Further analyses showed that R294K mutation in neuraminidase could remarkably decrease the binding energies for oseltamivir, while other small molecules showed stable binding abilities with mutated neuraminidase. Taken together, the molecular docking studies identified four potential inhibitors for neuraminidase of H7N9, which might be effective for the drug-resistant mutants.
Insights
New research identifies four natural compounds—quercetin, chlorogenic acid, baicalein, and oleanolic acid—as potential drugs against the avian influenza A (H7N9) virus. These compounds show promise against drug-resistant H7N9 strains, offering hope for new treatments.
Area of Science:
- Virology
- Drug Discovery
- Computational Chemistry
Background:
- Avian influenza A (H7N9) virus poses a significant public health threat due to its high lethality and pathogenicity.
- Emerging mutations, like neuraminidase R294K, can confer resistance to existing antiviral drugs such as oseltamivir.
- There is an urgent need for novel therapeutic agents effective against H7N9, particularly drug-resistant strains.
Purpose of the Study:
- To identify potential new drug candidates against the H7N9 virus.
- To explore the binding capabilities of natural small molecules with H7N9 neuraminidase, including drug-resistant variants.
- To evaluate the efficacy of quercetin, chlorogenic acid, baicalein, and oleanolic acid as inhibitors of H7N9 neuraminidase.
Main Methods:
- Molecular docking simulations were performed using H7N9 neuraminidase and an oseltamivir-resistant influenza virus neuraminidase as targets.
- Four natural compounds (quercetin, chlorogenic acid, baicalein, and oleanolic acid) were used as potential inhibitors (donors).
- Binding affinities between the small molecules and the neuraminidase targets were analyzed.
Main Results:
- Quercetin, chlorogenic acid, oleanolic acid, and baicalein demonstrated high binding potentials with H7N9 neuraminidase, comparable to oseltamivir.
- The R294K mutation significantly reduced the binding energy of oseltamivir.
- The four natural compounds maintained stable binding interactions with the mutated neuraminidase, suggesting efficacy against resistant strains.
Conclusions:
- Molecular docking studies identified quercetin, chlorogenic acid, baicalein, and oleanolic acid as promising inhibitors of H7N9 neuraminidase.
- These compounds show potential for developing new antiviral drugs effective against oseltamivir-resistant H7N9 mutants.
- Further investigation is warranted to validate these findings and develop new H7N9 therapeutics.
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