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《Nature，10月20日，Development of humanized tri-specific nanobodies with potent neutralization for SARS-CoV-2》

  • 来源专题：COVID-19科研动态监测
  • 编译者： zhangmin
  • 发布时间：2020-11-16

  • Development of humanized tri-specific nanobodies with potent neutralization for SARS-CoV-2

    Jianbo Dong, Betty Huang, Bo Wang, Allison Titong, Sachith Gallolu Kankanamalage, Zhejun Jia, Meredith Wright, Pannaga Parthasarathy & Yue Liu

    Scientific Reports volume 10, Article number: 17806 (2020)

    Abstract

    SARS-CoV-2 is a newly emergent coronavirus, which has adversely impacted human health and has led to the COVID-19 pandemic. There is an unmet need to develop therapies against SARS-CoV-2 due to its severity and lack of treatment options. A promising approach to combat COVID-19 is through the neutralization of SARS-CoV-2 by therapeutic antibodies. Previously, we described a strategy to rapidly identify and generate llama nanobodies (VHH) from naïve and synthetic humanized VHH phage libraries that specifically bind the S1 SARS-CoV-2 spike protein, and block the interaction with the human ACE2 receptor. In this study we used computer-aided design to construct multi-specific VHH antibodies fused to human IgG1 Fc domains based on the epitope predictions for leading VHHs. The resulting tri-specific VHH-Fc antibodies show more potent S1 binding, S1/ACE2 blocking, and SARS-CoV-2 pseudovirus neutralization than the bi-specific VHH-Fcs or combination of individual monoclonal VHH-Fcs. Furthermore, protein stability analysis of the VHH-Fcs shows favorable developability features, which enable them to be quickly and successfully developed into therapeutics against COVID-19.

  • 原文来源：https://www.nature.com/articles/s41598-020-74761-y
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