Identifying a Marine-Derived Small-Molecule Nucleoprotein Inhibitor Against Influenza A Virus
Zihan Wang1, Yang Zhang1, Shangjie Xu1
1Key Laboratory of Marine Drugs, School of Medicine and Pharmacy, Ocean University of China, Chinese Ministry of Education, 5 Yushan Road, Qingdao 266003, China.
Abstract:
Influenza A virus (IAV) poses a major threat to global public health, exerting immense pressure on human health and the economy. The IAV nucleoprotein (NP) is an ideal target for antiviral drug development. Through Mini-genome and Surface Plasmon Resonance assays, this study discovered and verified that mycophenolic acid methyl ester (MAE), a secondary metabolite produced by the marine algal-associated fungus Phaeosphaeria spartinae, can target the viral nucleoprotein to exert anti-IAV activity. Pull-down assays and immunofluorescence have revealed that MAE blocks the nuclear import of viral ribonucleoprotein complexes (vRNP) by interfering with the interaction between NP and IMP-α. It also affects the vRNP assembly process by regulating NP oligomerization and the interaction between NP and PB2. In addition, Sandwich ELISA and Electron Microscopy experiments showed that MAE can also inactivate viral particles to reduce the risk of infection. Comprehensive research results indicate that MAE exerts its effects by inhibiting the viral NP protein, which has laid an important foundation for the development of marine-derived NP-targeted drugs.
Insights
Mycophenolic acid methyl ester (MAE), derived from marine fungus, shows potent anti-influenza A virus (IAV) activity. MAE targets the viral nucleoprotein (NP), inhibiting viral replication and inactivating virus particles.
Area of Science:
- Marine biotechnology
- Virology
- Drug discovery
Background:
- Influenza A virus (IAV) presents a significant global health and economic burden.
- The IAV nucleoprotein (NP) is a promising target for antiviral therapies.
Purpose of the Study:
- To identify and characterize novel anti-IAV compounds from marine natural products.
- To investigate the mechanism of action of mycophenolic acid methyl ester (MAE) against IAV.
Main Methods:
- Mini-genome assays, Surface Plasmon Resonance (SPR) for activity screening.
- Pull-down assays, immunofluorescence, Sandwich ELISA, and Electron Microscopy for mechanistic studies.
Main Results:
- Mycophenolic acid methyl ester (MAE) from *Phaeosphaeria spartinae* demonstrated significant anti-IAV activity.
- MAE inhibits IAV replication by blocking NP nuclear import and affecting vRNP assembly.
- MAE also inactivates viral particles, reducing infectivity.
Conclusions:
- MAE is a marine-derived compound targeting IAV nucleoprotein (NP) with dual antiviral mechanisms.
- This discovery provides a foundation for developing novel marine-based NP-targeted influenza drugs.
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