n/a
Abstract Title:

The Antimalaria Drug Artesunate Inhibits Porcine Reproductive and Respiratory Syndrome Virus Replication via Activating AMPK and Nrf2/HO-1 Signaling Pathways.

Abstract Source:

J Virol. 2021 Nov 17:JVI0148721. Epub 2021 Nov 17. PMID: 34787456

Abstract Author(s):

Feixiang Long, Mingxin Zhang, Xia Yang, Xiaohuan Liang, Lizhan Su, Tongqing An, Guihong Zhang, Zhenling Zeng, Yahong Liu, Weisan Chen, Jianxin Chen

Article Affiliation:

Feixiang Long

Abstract:

Porcine Reproductive and Respiratory Syndrome virus (PRRSV) causes significant economic losses to the pork industry worldwide. Currently, vaccine strategies provide limited protection against PRRSV transmission, and no effective drug is commercially available. Therefore, there is an urgent need to develop novel antiviral strategies to prevent PRRSV pandemics. This study showed that artesunate (AS), one of the antimalarial drugs, potently suppressed PRRSV replication in Marc-145 cells andprimary porcine alveolar macrophages (PAMs) at micromolar concentrations. Furthermore, we demonstrated that this suppression was closely associated with AS-activated AMPK (energy homeostasis) and Nrf2/HO-1 (inflammation) signaling pathways. AS treatment promoted p-AMPK, Nrf2 and HO-1 expression, and thus inhibited PRRSV replication in Marc-145 and PAM cells in a time- and dose-dependent manner. These effects of AS were reversed when AMPK or HO-1 gene was silenced by siRNA. In addition, we demonstrated that AMPK works upstream of Nrf2/HO-1 as its activation by AS is AMPK-dependent. Adenosine phosphate analysis showed that AS activates AMPK via improving AMP/ADP:ATP ratio rather than direct interaction with AMPK. Altogether, our findings indicate that AS could be a promising novel therapeutics for controlling PRRSV and that its anti-PRRSV mechanism, which involves the functional link between energy homeostasis and inflammation suppression pathways, may provide opportunities for developing novel antiviral agents.Porcine reproductive and respiratory syndrome virus (PRRSV) infections have been continuously threatened the pork industry worldwide. Vaccination strategies provide very limited protection against PRRSV infection, and no effective drug is commercially available. We show that artesunate (AS), one of the antimalarial drugs, is a potent inhibitor against PRRSV replication in Marc-145 cells andprimary porcine alveolar macrophages (PAMs). Furthermore, we demonstrate that AS inhibits PRRSV replication via activation of AMPK-dependent Nrf2/HO-1 signaling pathways, revealing a novel link between energy homeostasis (AMPK) and inflammation suppression (Nrf2/HO-1) during viral infection. Therefore, we believe that AS may be a promising novel therapeutics for controlling PRRSV, and its anti-PRRSV mechanism may provide a potential strategy to develop novel antiviral agents.

Study Type : Animal Study

Print Options


Key Research Topics

Sayer Ji
Founder of GreenMedInfo.com

Subscribe to our informative Newsletter & get Nature's Evidence-Based Pharmacy

Our newsletter serves 500,000 with essential news, research & healthy tips, daily.

Download Now

500+ pages of Natural Medicine Alternatives and Information.

This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.

© Copyright 2008-2022 GreenMedInfo.com, Journal Articles copyright of original owners, MeSH copyright NLM.