Broad neutralizing nanobody against SARS-CoV-2 engineered from pre-designed synthetic library

Liu, Q.; Cai, C.; Huang, Y.; Zhou, L.; Guan, Y.; Fu, S.; Lin, Y.; Yang, T.; Liang, X.; Wang, N.; Zhang, F.; Sun, Q.; Bai, Y.; Chen, Y.; Yan, H.; Zhang, Z.; Lan, K.; Li, X.; Hou, S.-C.; Xiong, Y.

doi:10.1101/2021.08.07.455523

bioRxiv · 10.1101/2021.08.07.455523

Broad neutralizing nanobody against SARS-CoV-2 engineered from pre-designed synthetic library

Liu, Q.·Cai, C.·Huang, Y.·Zhou, L.·Guan, Y.·Fu, S.·Lin, Y.·Yang, T.·Liang, X.·Wang, N.·Zhang, F.·Sun, Q.·Bai, Y.·Chen, Y.·Yan, H.·Zhang, Z.·Lan, K.·Li, X.·Hou, S.-C.·Xiong, Y.

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Abstract

SARS-CoV-2 infection is initiated with Spike glycoprotein binding to the receptor of human angiotensin converting enzyme 2 via its receptor binding domain. Blocking this interaction is considered as an effective approach to inhibit virus infection. Here we report the discovery of a neutralizing nanobody, VHH60, directly produced from a humanized synthetic nanobody library. VHH60 competes with human ACE2 to bind the receptor binding domain of the Spike protein with a KD of 2.56 nM, inhibits infections of both live SARS-CoV-2 and pseudotyped viruses harboring wildtype, escape mutations and prevailing variants at nanomolar level. VHH60 also suppresses SARS-CoV-2 infection and propagation 50-fold better and protects mice from death two times longer than that of control group after live virus inoculation on mice. VHH60 therefore is a powerful synthetic nanobody with a promising profile for disease control against COVID19.

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Liu, Q., Cai, C., Huang, Y., Zhou, L., Guan, Y., Fu, S., Lin, Y., Yang, T., Liang, X., Wang, N., Zhang, F., Sun, Q., Bai, Y., Chen, Y., Yan, H., Zhang, Z., Lan, K., Li, X., Hou, S.-C., Xiong, Y.. 2021-08-09. Broad neutralizing nanobody against SARS-CoV-2 engineered from pre-designed synthetic library. https://doi.org/10.1101/2021.08.07.455523

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