2020
DOI: 10.1038/s41598-020-74761-y
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Development of humanized tri-specific nanobodies with potent neutralization for SARS-CoV-2

Abstract: SARS-CoV-2 is a newly emergent coronavirus, which has adversely impacted human health and has led to the COVID-19 pandemic. There is an unmet need to develop therapies against SARS-CoV-2 due to its severity and lack of treatment options. A promising approach to combat COVID-19 is through the neutralization of SARS-CoV-2 by therapeutic antibodies. Previously, we described a strategy to rapidly identify and generate llama nanobodies (VHH) from naïve and synthetic humanized VHH phage libraries that specifically b… Show more

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Cited by 65 publications
(66 citation statements)
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“…Hence, RBD-targeting antibodies hold promise as prophylactics and therapeutics for SARS-CoV-2. Here, seven unique Nbs were isolated from RBD-immunized alpacas, and amino on May 11, 2021 by guest http://jvi.asm.org/ Downloaded from acid sequence alignment shows CDR sequences of these Nbs are distinct from other reported Nbs (34)(35)(36)(37)(38)(39)(40)(41)(42). Four of the Nbs exhibited a high affinity of low-nanomolar K D (Fig.…”
Section: Discussionmentioning
confidence: 84%
“…Hence, RBD-targeting antibodies hold promise as prophylactics and therapeutics for SARS-CoV-2. Here, seven unique Nbs were isolated from RBD-immunized alpacas, and amino on May 11, 2021 by guest http://jvi.asm.org/ Downloaded from acid sequence alignment shows CDR sequences of these Nbs are distinct from other reported Nbs (34)(35)(36)(37)(38)(39)(40)(41)(42). Four of the Nbs exhibited a high affinity of low-nanomolar K D (Fig.…”
Section: Discussionmentioning
confidence: 84%
“…Furthermore, the trivalent version of Nb6 (Nb6-tri) has shown an improvement in the neutralization activity against the authentic SARS-CoV-2 (IC 50 : 140 pM) [ 252 ]. In addition, multi-specific V H H Abs fused to human IgG1 Fc domains are able to activate the Fc-dependent functions, such as tri-specific V H H-Fc 3F-1B-2A, which has been designed to neutralize SARS-CoV-2 [ 253 ]. The tri-specific V H H-Fc 3F-1B-2A Ab, which in a docking model has been observed to interact with the RBD, exhibits higher pseudovirus neutralization activity than that by other V H H-Fc combinations (IC 50 : 3.0 nM) [ 253 ] (Additional file 1 : Table S5).…”
Section: Insights From Ab Therapeutic Strategies Against Sars-cov-2 Infectionmentioning
confidence: 99%
“…In addition, multi-specific V H H Abs fused to human IgG1 Fc domains are able to activate the Fc-dependent functions, such as tri-specific V H H-Fc 3F-1B-2A, which has been designed to neutralize SARS-CoV-2 [ 253 ]. The tri-specific V H H-Fc 3F-1B-2A Ab, which in a docking model has been observed to interact with the RBD, exhibits higher pseudovirus neutralization activity than that by other V H H-Fc combinations (IC 50 : 3.0 nM) [ 253 ] (Additional file 1 : Table S5). Other Nbs have been obtained from camelid V H H naïve and synthetic libraries.…”
Section: Insights From Ab Therapeutic Strategies Against Sars-cov-2 Infectionmentioning
confidence: 99%
“…CoV-X2, unlike other multispecifics 27 , is a fully human IgG-like molecule. As such, it has favorable developability and could be further engineered to alter effector functions.…”
mentioning
confidence: 99%