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.; Chen, Y.; Li, X.; Hou, S.-C.; Xiong, Y.
Show 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.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.