{Reference Type}: Journal Article
{Title}: A broad neutralizing nanobody against SARS-CoV-2 engineered from an approved drug.
{Author}: Liu Q;Lu Y;Cai C;Huang Y;Zhou L;Guan Y;Fu S;Lin Y;Yan H;Zhang Z;Li X;Yang X;Yang H;Guo H;Lan K;Chen Y;Hou SC;Xiong Y;
{Journal}: Cell Death Dis
{Volume}: 15
{Issue}: 6
{Year}: 2024 Jun 28
暂无{DOI}: 10.1038/s41419-024-06802-7
{Abstract}: SARS-CoV-2 infection is initiated by Spike glycoprotein binding to the human angiotensin-converting enzyme 2 (ACE2) receptor via its receptor binding domain. Blocking this interaction has been proven to be an effective approach to inhibit virus infection. Here we report the discovery of a neutralizing nanobody named VHH60, which was directly produced from an engineering nanobody library based on a commercialized nanobody within a very short period. VHH60 competes with human ACE2 to bind the receptor binding domain of the Spike protein at S351, S470-471and S493-494 as determined by structural analysis, with an affinity of 2.56 nM. It inhibits infections of both ancestral SARS-CoV-2 strain and pseudotyped viruses harboring SARS-CoV-2 wildtype, key mutations or variants at the nanomolar level. Furthermore, VHH60 suppressed SARS-CoV-2 infection and propagation 50-fold better and protected mice from death for twice as long as the control group after SARS-CoV-2 nasal infections in vivo. Therefore, VHH60 is not only a powerful nanobody with a promising profile for disease control but also provides evidence for a highly effective and rapid approach to generating therapeutic nanobodies.