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槲皮素作为一种抗病毒剂,在体外和体内均能抑制伪狂犬病病毒。

Quercetin as an antiviral agent inhibits the Pseudorabies virus in vitro and in vivo.

作者信息

Sun Yumei, Li Chang, Li Zhonghua, Shangguan Aishao, Jiang Jinhe, Zeng Wei, Zhang Shujun, He Qigai

机构信息

Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction Ministry of Education, Huazhong Agricultural University, Wuhan 430070, China; State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430000, China.

State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430000, China.

出版信息

Virus Res. 2021 Nov;305:198556. doi: 10.1016/j.virusres.2021.198556. Epub 2021 Sep 4.

Abstract

Pseudorabies virus (PRV) accounts for a critical swine disease incurring economic losses worldwide. Several PRV vaccines are commercially available but these vaccines are effective against only certain prevalent PRV strains in China. To prevent PRV-induced latent infection and decrease the pathogenicity, novel anti-PRV drugs are required to prevent PRV infection. Natural products show exceptional structural diversity representing an important source for developing novel therapeutic agents. Quercetin is a flavonoid with anti-oxidant, anti-cancer, anti-bacterial and anti-viral activities. This study involved quercetin for studying the anti-PRV function in vitro and in vivo. Quercetin was found to significantly decrease the PRV virulent strain HNX at a half-maximal inhibitory concentration (IC) of 2.618 μM and selectivity index 229. This anti-PRV activity of quercetin was found to be dose-dependent. Furthermore, quercetin also inhibited a wide the infections by a spectrum of PRV strains like HNX, Ea, Bartha and Fa strain. These virucidal effects of quercetin suggest the interaction between these molecules and viral particles, and quercetin is responsible for inhibiting the adsorption of PRV infections. The silico assays suggesting that quercetin might interact with the gD-protein on the surface of the PRV important for viral infection. Additional, the quercetin plantar injection protected the mice from the lethal challenge, decreasing the PRV-infected mice's brain viral loads and mortality. These results provides a anti-PRV strategy and contribute to drug discovery and development.

摘要

伪狂犬病病毒(PRV)是一种导致全球养猪业经济损失的重要猪病病原体。目前已有多种PRV疫苗上市,但这些疫苗仅对中国部分流行的PRV毒株有效。为预防PRV引起的潜伏感染并降低其致病性,需要新型抗PRV药物来预防PRV感染。天然产物具有独特的结构多样性,是开发新型治疗药物的重要来源。槲皮素是一种具有抗氧化、抗癌、抗菌和抗病毒活性的黄酮类化合物。本研究旨在探讨槲皮素在体外和体内的抗PRV功能。结果发现,槲皮素对PRV强毒株HNX具有显著的抑制作用,其半数抑制浓度(IC)为2.618 μM,选择性指数为229。槲皮素的抗PRV活性呈剂量依赖性。此外,槲皮素还能抑制多种PRV毒株(如HNX、Ea、Bartha和Fa毒株)的感染。槲皮素的这些杀病毒作用表明这些分子与病毒颗粒之间存在相互作用,且槲皮素负责抑制PRV感染的吸附。计算机模拟分析表明,槲皮素可能与PRV表面对病毒感染至关重要的gD蛋白相互作用。此外,经足底注射槲皮素可保护小鼠免受致死性攻击,降低PRV感染小鼠的脑病毒载量和死亡率。这些结果为抗PRV策略提供了依据,并有助于药物的发现和开发。

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