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Griffithsin 抑制尼帕病毒进入和融合,可保护叙利亚金黄地鼠免受致命尼帕病毒的挑战。

Griffithsin Inhibits Nipah Virus Entry and Fusion and Can Protect Syrian Golden Hamsters From Lethal Nipah Virus Challenge.

机构信息

Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.

出版信息

J Infect Dis. 2020 May 11;221(Supplement_4):S480-S492. doi: 10.1093/infdis/jiz630.

Abstract

Nipah virus (NiV) is a highly pathogenic zoonotic paramyxovirus that causes fatal encephalitis and respiratory disease in humans. There is currently no approved therapeutic for human use against NiV infection. Griffithsin (GRFT) is high-mannose oligosaccharide binding lectin that has shown in vivo broad-spectrum activity against viruses, including severe acute respiratory syndrome coronavirus, human immunodeficiency virus 1, hepatitis C virus, and Japanese encephalitis virus. In this study, we evaluated the in vitro antiviral activities of GRFT and its synthetic trimeric tandemer (3mG) against NiV and other viruses from 4 virus families. The 3mG had comparatively greater potency than GRFT against NiV due to its enhanced ability to block NiV glycoprotein-induced syncytia formation. Our initial in vivo prophylactic evaluation of an oxidation-resistant GRFT (Q-GRFT) showed significant protection against lethal NiV challenge in Syrian golden hamsters. Our results warrant further development of Q-GRFT and 3mG as potential NiV therapeutics.

摘要

寨卡病毒(NiV)是一种高致病性人畜共患副粘病毒,可导致人类致命性脑炎和呼吸道疾病。目前尚无针对 NiV 感染的经批准的人类治疗方法。Griffithsin(GRFT)是一种高甘露糖寡糖结合凝集素,已在体内显示出对多种病毒的广谱活性,包括严重急性呼吸综合征冠状病毒、人类免疫缺陷病毒 1、丙型肝炎病毒和日本脑炎病毒。在这项研究中,我们评估了 GRFT 及其合成三聚体(3mG)对 NiV 以及来自 4 种病毒科的其他病毒的体外抗病毒活性。由于 3mG 增强了阻断 NiV 糖蛋白诱导的合胞体形成的能力,因此与 GRFT 相比,其对 NiV 的效力相对更大。我们对氧化还原稳定的 GRFT(Q-GRFT)的初步体内预防性评估表明,它对叙利亚金黄地鼠的致命 NiV 攻击具有显著的保护作用。我们的研究结果证明了 Q-GRFT 和 3mG 作为潜在的 NiV 治疗药物的进一步开发是合理的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9caf/7213580/8cac10c0ca05/jiz630f0001.jpg

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