Abstract
The dramatically expanding coronavirus disease 2019 (COVID-19) needs multiple effective countermeasures. Neutralizing nanobodies (Nbs) are a potential therapeutic strategy for treating COVID-19. Here, we characterize several receptor binding domain (RBD)-specific Nbs isolated from an Nb library derived from an alpaca immunized with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (S); among them, three Nbs exhibit picomolar potency against SARS-CoV-2 live virus, pseudotyped viruses, and circulating SARS-CoV-2 variants. To improve their efficacy, various configurations of Nbs are engineered. Nb 15 -Nb H -Nb 15 , a trimer constituted of three Nbs, is constructed to be bispecific for human serum albumin (HSA) and RBD of SARS-CoV-2. Nb 15 -Nb H -Nb 15 exhibits single-digit ng/ml neutralization potency against the wild-type and Delta variants of SARS-CoV-2 with a long half-life in vivo. In addition, we show that intranasal administration of Nb 15 -Nb H -Nb 15 provides effective protection for both prophylactic and therapeutic purposes against SARS-CoV-2 infection in transgenic hACE2 mice. Nb 15 -Nb H -Nb 15 is a potential candidate for both the prevention and treatment of SARS-CoV-2 through respiratory administration.
Keywords: Delta; Nb15; Nb15-NbH-Nb15; SARS-CoV-2; VHH; bispecific; hACE2 mice; intranasal; nanobody; potent neutralizing.
【저자키워드】 SARS-CoV-2, Delta, nanobody, intranasal, bispecific, Nb15, Nb15-NbH-Nb15, VHH, hACE2 mice, potent neutralizing., 【초록키워드】 COVID-19, Treatment, coronavirus disease, Coronavirus disease 2019, Efficacy, coronavirus, SARS-COV-2 infection, spike glycoprotein, Prophylactic, severe acute respiratory syndrome Coronavirus, delta variant, hACE2, Receptor binding domain, SARS-CoV-2 variants, mice, albumin, Neutralizing, respiratory, in vivo, alpaca, Pseudotyped viruses, therapeutic strategy, intranasal, Live virus, administration, acute respiratory syndrome, Human serum albumin, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, neutralization potency, trimer, wild-type, treating COVID-19, circulating SARS-CoV-2 variants, RBD of SARS-CoV-2, transgenic, effective, immunized, IMPROVE, addition, provide, exhibit, therapeutic purpose, 【제목키워드】 mice, administration, PROTECT,