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Open AccessArticle

Chenodeoxycholic Acid from Bile Inhibits Influenza A Virus Replication via Blocking Nuclear Export of Viral Ribonucleoprotein Complexes

1
Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China
2
Hygiene Detection Center, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou 510515, China
3
Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia
*
Authors to whom correspondence should be addressed.
Molecules 2018, 23(12), 3315; https://doi.org/10.3390/molecules23123315
Received: 19 October 2018 / Revised: 10 December 2018 / Accepted: 12 December 2018 / Published: 14 December 2018
(This article belongs to the Special Issue Recent Advances in the Development of Antiviral Agents)
Influenza A virus (IAV) infection is still a major global threat for humans, especially for the risk groups: young children and the elderly. The currently licensed antiviral drugs target viral factors and are prone to viral resistance. In recent years, a few endogenous small molecules from host, such as estradiol and omega-3 polyunsaturated fatty acid (PUFA)-derived lipid mediator protection D1 (PD1), were demonstrated to be capable of inhibiting IAV infection. Chenodeoxycholic acid (CDCA), one of the main primary bile acids, is synthesized from cholesterol in the liver and classically functions in emulsification and absorption of dietary fats. Clinically, CDCA has been used in the treatment of patients with cholesterol gallstones for more than five decades. In this study, we showed that CDCA attenuated the replication of three subtypes of influenza A virus, including a highly pathogenic H5N1 strain, in A549 and MDCK cell cultures with IC50 ranging from 5.5 to 11.5 μM. Mechanistically, CDCA effectively restrained the nuclear export of viral ribonucleoprotein (vRNP) complexes. In conclusion, as an endogenous physiological small molecule, CDCA can inhibit IAV replication in vitro, at least in part, by blocking vRNP nuclear export, and affords further studies for development as a potential antiviral agent against IAV infections. View Full-Text
Keywords: chenodeoxycholic acid (CDCA); influenza A virus; A549 cells; MDCK cells; nuclear export of viral ribonucleoprotein (vRNP) chenodeoxycholic acid (CDCA); influenza A virus; A549 cells; MDCK cells; nuclear export of viral ribonucleoprotein (vRNP)
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Luo, L.; Han, W.; Du, J.; Yang, X.; Duan, M.; Xu, C.; Zeng, Z.; Chen, W.; Chen, J. Chenodeoxycholic Acid from Bile Inhibits Influenza A Virus Replication via Blocking Nuclear Export of Viral Ribonucleoprotein Complexes. Molecules 2018, 23, 3315.

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