在SARS-CoV-2动物模型中具有双对应的人类VH域的高强度
Wei Li1, Alexandra Schäfer2, Swarali S Kulkarni3
1Center for Antibody Therapeutics, Division of Infectious Diseases, Department of Medicine, University of Pittsburgh Medical School, 3550 Terrace St., Pittsburgh, PA 15261, USA.
Cell
|September 17, 2020
概括
一种新型抗体片段VH-Fc ab8有效中和SARS-CoV-2,在动物模型中显示出强大的治疗和预防效果. 这种有前途的COVID-19治疗候选药物向S糖蛋白并干扰病毒的进入.
科学领域:
- 免疫学
- 病毒学
- 药物发现
背景情况:
- 迫切需要针对COVID-19的新疗法.
- 开发针对SARS-CoV-2尖端 (S) 糖蛋白的基于抗体的治疗方法.
研究的目的:
- 识别和表征一种高亲和度的人类抗体VH域结合剂,用于潜在的COVID-19治疗用途.
- 评估已识别的VH- Fc ab8抗体的中和能力和体内疗效.
主要方法:
- 产生菌体显示的人类抗体VH域库.
- 对VH-Fc ab8与SARS-CoV-2 S糖蛋白和突变体的结合亲和力和热情的表征.
- 在体外和体内评估VH- Fc ab8中和活性 (小鼠和仓鼠).
- 使用电子显微镜和扫描突变的结构分析,以确定中和的机制.
主要成果:
- 鉴定了一种高亲和度VH结合剂ab8,该结合剂被改造为VH-Fc ab8.
- 在实验室和体内,VH-Fc ab8 证明了SARS-CoV-2 的强烈中和,在子模型中具有很高的预防和治疗效果.
- 结构研究显示ab8与所有三种S质体相互作用,阻断ACE2结合.
- VH- Fc ab8表现出有利的发育性质,包括没有聚合,也没有与人体蛋白质结合.
结论:
- VH-Fc ab8是一种强大的中和抗体,对SARS-CoV-2突变具有交叉反应性.
- 它在动物模型中的有效性和有利的可开发性概况支持其作为COVID-19治疗候选者的进展.
更多相关视频
08:41Live Imaging and Quantification of Viral Infection in K18 hACE2 Transgenic Mice Using Reporter-Expressing Recombinant SARS-CoV-2
Published on: November 5, 2021
3.1K
06:08Author Spotlight: A Pseudotype Virus System for Assessing Omicron Subvariants and Neutralizing Antibodies in SARS-CoV-2 Research
Published on: September 8, 2023
1.6K
相关概念视频
01:29Viruses with RNA Genomes
1.5K
RNA viruses are categorized into positive-strand, negative-strand, or double-stranded groups based on their genomic structure and replication mechanisms. This classification dictates how they exploit host cellular machinery for protein synthesis and replication. Some RNA viruses also utilize reverse transcription as part of their life cycle, further diversifying their replication strategies.Positive-Strand RNA VirusesPositive-strand RNA viruses have genomes that function directly as messenger...
1.5K
01:26Human Virome
47
The human body harbors a vast and diverse viral community known as the human virome. The virome includes bacteriophages that infect bacteria, and eukaryotic viruses that infect human cells. Transient dietary and environmental viruses also contribute to this dynamic ecosystem. Estimates suggest the human body may contain on the order of 10¹³ viral particles, though abundance varies widely by body site and detection method.Comprehensive characterization of the virome has become possible...
47
01:25Arboviral Encephalitis
59
Arboviral encephalitis refers to brain inflammation caused by arthropod-borne viruses, particularly those transmitted through mosquito vectors. Among these, West Nile virus (WNV), a member of the Flaviviridae family, is a significant public health concern. WNV is an enveloped, positive-sense, single-stranded RNA virus. Human infection typically begins when an infected mosquito introduces the virus into the dermis during feeding. The primary transmission cycle involves birds as amplifying hosts...
59