**Ginsenoside Rg1 Suppresses Type 2 PRRSV Infection via NF-**κ**B Signaling Pathway In Vitro, and Provides Partial Protection against HP-PRRSV in Piglet**

**Zhi-qing Yu 1,2, He-you Yi 1,2, Jun Ma 1,2, Ying-fang Wei 1,2, Meng-kai Cai 1,2, Qi Li 1,2, Chen-xiao Qin 1,2, Yong-jie Chen 2, Xiao-liang Han 1,2, Ru-ting Zhong 1,2, Yao Chen 3, Guan Liang 1,2, Qiwei Deng 1,2, Kegong Tian 4,5, Heng Wang 1,2,\* and Gui-hong Zhang 1,2,\***


Received: 15 October 2019; Accepted: 7 November 2019; Published: 9 November 2019

**Abstract:** Porcine reproductive and respiratory syndrome virus (PRRSV) is a huge threat to the modern pig industry, and current vaccine prevention strategies could not provide full protection against it. Therefore, exploring new anti-PRRSV strategies is urgently needed. Ginsenoside Rg1, derived from ginseng and notoginseng, is shown to exert anti-inflammatory, neuronal apoptosis-suppressing and anti-oxidant effects. Here we demonstrate Rg1-inhibited PRRSV infection both in Marc-145 cells and porcine alveolar macrophages (PAMs) in a dose-dependent manner. Rg1 treatment affected multiple steps of the PRRSV lifecycle, including virus attachment, replication and release at concentrations of 10 or 50 μM. Meanwhile, Rg1 exhibited broad inhibitory activities against Type 2 PRRSV, including highly pathogenic PRRSV (HP-PRRSV) XH-GD and JXA1, NADC-30-like strain HNLY and classical strain VR2332. Mechanistically, Rg1 reduced mRNA levels of the pro-inflammatory cytokines, including IL-1β, IL-8, IL-6 and TNF-α, and decreased NF-κB signaling activation triggered by PRRSV infection. Furthermore, 4-week old piglets intramuscularly treated with Rg1 after being challenged with the HP-PRRSV JXA1 strain display moderate lung injury, decreased viral load in serum and tissues, and an improved survival rate. Collectively, our study provides research basis and supportive clinical data for using Ginsenoside Rg1 in PRRSV therapies in swine.

**Keywords:** porcine reproductive and respiratory syndrome virus; ginsenoside Rg1; antiviral activity; pro-inflammatory factor; NF-κB signaling pathway
