Inhibition of influenza a virus infection by natural stilbene piceatannol targeting virus hemagglutinin

Lianghao Huang; Jinyu Wang; Xiaoyao Ma; Lishan Sun; Cui Hao; Wei Wang

doi:10.1016/j.phymed.2023.155058

Inhibition of influenza a virus infection by natural stilbene piceatannol targeting virus hemagglutinin

Phytomedicine. 2023 Nov:120:155058. doi: 10.1016/j.phymed.2023.155058. Epub 2023 Aug 30.

Authors

Lianghao Huang¹, Jinyu Wang¹, Xiaoyao Ma¹, Lishan Sun¹, Cui Hao², Wei Wang³

Affiliations

¹ Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
² Medical Research Center, Affiliated Hospital of Qingdao University, Qingdao 266003, China. Electronic address: haocui@qduhospital.cn.
³ Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China; Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China. Electronic address: wwwakin@ouc.edu.cn.

PMID: 37690231
DOI: 10.1016/j.phymed.2023.155058

Abstract

Background: Given the magnitude of influenza pandemics as a threat to the global population, it is crucial to have as many prevention and treatment options as possible. Piceatannol (PIC) is a tetrahydroxylated stilbenoid (trans-3,4,3',5'-tetrahydroxystilbene), also known as 3'- hydroxy resveratrol, which has demonstrated many different biological activities such as anti-inflammatory and antiviral activities.

Purpose: In this study, the anti-influenza A virus (IAV) activities and mechanisms of PIC in vitro and in vivo were investigated in order to provide reference for the development of novel plant-derived anti-IAV drugs.

Methods: The viral plaque assay, RT-PCR and western blot assay were used to evaluate the anti-IAV effects of PIC in vitro. The anti-IAV mechanism of PIC was determined by HA syncytium assay, DARTS assay and Surface Plasmon Resonance assay. The mouse pneumonia model combined with HE staining were used to study the anti-IAV effects of PIC in vivo.

Results: PIC shows inhibition on the multiplication of both H1N1 and H3N2 viruses, and blocks the infection of H5N1 pseudovirus with low toxicity. PIC may directly act on the envelope of IAV to induce the rupture and inactivation of IAV particles. PIC can also block membrane fusion via binding to HA2 rather than HA1 and cleavage site of HA0. PIC may interact with the two residues (HA2-T68 and HA2-I75) of HA2 to block the conformational change of HA so as to inhibit membrane fusion. Importantly, oral therapy of PIC also markedly improved survival and reduced viral titers in IAV-infected mice.

Conclusion: PIC possesses significant anti-IAV effects both in vitro and in vivo and may block IAV infection mainly through interaction with HA to block membrane fusion. Thus, PIC has the potential to be developed into a new broad-spectrum anti-influenza drug for the prevention and treatment of influenza.

Keywords: Hemagglutinin; Influenza a virus; Membrane fusion; Piceatannol; Virucidal effect.

MeSH terms

Animals
Disease Models, Animal
Hemagglutinins
Humans
Influenza A Virus, H1N1 Subtype*
Influenza A Virus, H3N2 Subtype
Influenza A Virus, H5N1 Subtype*
Influenza A virus*
Influenza, Human* / drug therapy
Mice
Stilbenes* / pharmacology

Substances

3,3',4,5'-tetrahydroxystilbene
Hemagglutinins
Stilbenes