Antibodies binding to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike have therapeutic promise, but emerging variants show the potential for virus escape. This emphasizes the need for therapeutic molecules with distinct and novel neutralization mechanisms. Here we describe the isolation of a nanobody that interacts simultaneously with two RBDs from different spike trimers of SARS-CoV-2, rapidly inducing the formation of spike trimer–dimers leading to the loss of their ability to attach to the host cell receptor, ACE2. We show that this nanobody potently neutralizes SARS-CoV-2, including the beta and delta variants, and cross-neutralizes SARS-CoV. Furthermore, we demonstrate the therapeutic potential of the nanobody against SARS-CoV-2 and the beta variant in a human ACE2 transgenic mouse model. This naturally elicited bispecific monomeric nanobody establishes an uncommon strategy for potent inactivation of viral antigens and represents a promising antiviral against emerging SARS-CoV-2 variants. Here, the authors isolate and characterize a bispecific monomeric nanobody that induces dimerization of SARS-CoV-2 spike trimers, neutralizes variants of concerns as well as SARS-CoV, and inhibits SARS-CoV-2 infection in mice.
【저자키워드】 SARS-CoV-2, viral infection, 【초록키워드】 ACE2, coronavirus, Antiviral, SARS-CoV, neutralization, SARS-COV-2 infection, variant, variants of concern, severe acute respiratory syndrome Coronavirus, virus, variants, human ACE2, Viral, nanobody, SARS-CoV-2 variants, mice, RBD, inactivation, therapeutic, Isolation, Beta, mechanisms, respiratory, Beta variant, binding, SARS-CoV-2 spike, Delta variants, cross-neutralize, RBDs, host cell, Viral antigen, acute respiratory syndrome, Therapeutic molecule, viral antigens, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, therapeutic potential, host cell receptor, antibodies binding, spike trimer, therapeutic molecules, Transgenic mouse, neutralize, Trimers, inhibit, interact, induce, elicited, monomeric, 【제목키워드】 in vivo, neutralize, induce, monomeric,