A nanobody recognizes a unique conserved epitope and potently neutralizes SARS-CoV-2 omicron variants

Modhiran, Naphak; Lauer, Simon; Amarilla, Alberto A.; Hewins, Peter; Broek, Sara Irene Lopes van den; Low, Yu Shang; Thakur, Nazia; Liang, Bojian; Nieto, Guillermo Valenzuela; Jung, James; Paramitha, Devina; Isaacs, Ariel; Sng, Julian D. J.; Song, David H.; Jørgensen, Jesper Tranekjær; Cheuquemilla, Yorka; Bürger, Jörg; Andersen, Ida Vang; Himelreichs, Johanna; Jara, Ronald; MacLoughlin, Ronan; Miranda-Chacón, Zaray; Chaná-Cuevas, Pedro; Kramer, Vasko; Spahn, C.M.T.; Mielke, Thorsten; Khromykh, Alexander A.; Munro, Trent; Jones, Martina L.; Young, Paul R.; Chappell, Keith J.; Bailey, Dalan; Kjær, Andreas; Herth, Matthias M.; Jurado, Kellie Ann; Schwefel, David; Rojas-Fernández, Alejandro; Watterson, Daniel

doi:10.1016/j.isci.2023.107085

Cited by 5 publications

(2 citation statements)

References 80 publications

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“… 62 ); anti-SARS-CoV-2 Spike protein, 1:1,000 (ref. 63 ); anti-γH2AX (Millipore, 1:1,000, no. 05-636); anti-TH (Invitrogen, 1:1,000, no.…”

Section: Methodsmentioning

confidence: 99%

Senolytic therapy alleviates physiological human brain aging and COVID-19 neuropathology

Aguado,

Amarilla,

Taherian Fard

et al. 2023

Nat Aging

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Aging is a major risk factor for neurodegenerative diseases, and coronavirus disease 2019 (COVID-19) is linked to severe neurological manifestations. Senescent cells contribute to brain aging, but the impact of virus-induced senescence on neuropathologies is unknown. Here we show that senescent cells accumulate in aged human brain organoids and that senolytics reduce age-related inflammation and rejuvenate transcriptomic aging clocks. In postmortem brains of patients with severe COVID-19 we observed increased senescent cell accumulation compared with age-matched controls. Exposure of human brain organoids to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induced cellular senescence, and transcriptomic analysis revealed a unique SARS-CoV-2 inflammatory signature. Senolytic treatment of infected brain organoids blocked viral replication and prevented senescence in distinct neuronal populations. In human-ACE2-overexpressing mice, senolytics improved COVID-19 clinical outcomes, promoted dopaminergic neuron survival and alleviated viral and proinflammatory gene expression. Collectively our results demonstrate an important role for cellular senescence in driving brain aging and SARS-CoV-2-induced neuropathology, and a therapeutic benefit of senolytic treatments.

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“… 62 ); anti-SARS-CoV-2 Spike protein, 1:1,000 (ref. 63 ); anti-γH2AX (Millipore, 1:1,000, no. 05-636); anti-TH (Invitrogen, 1:1,000, no.…”

Section: Methodsmentioning

confidence: 99%

Senolytic therapy alleviates physiological human brain aging and COVID-19 neuropathology

Aguado,

Amarilla,

Taherian Fard

et al. 2023

Nat Aging

Self Cite

View full text Add to dashboard Cite

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“…Traditional techniques for identifying broad-spectrum nanobodies encompass the enzyme-linked immunosorbent assay (ELISA) and pseudovirus-based neutralization assays. − For example, in 2020, Wrapp et al isolated and prepared a bivalent nanobody (VHH-72-Fc) that effectively neutralizes SARS-CoV-2 S pseudoviruses through ELISA . Similarly, previous research identified 127 variable domains of heavy chain antibody (VHH) clones with strong binding for the RBD with ELISA.…”

Section: Introductionmentioning

confidence: 99%

Proteomics Platform Reveals Broad-Spectrum Nanobodies for SARS-CoV-2 Variant Neutralization

Zhang,

Huang,

Zhang

et al. 2024

J. Proteome Res.

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The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the emergence of different variants of concerns with immune evasion that have been prevalent over the past three years. Nanobodies, the functional variable regions of camelid heavy-chain-only antibodies, have garnered interest in developing neutralizing antibodies due to their smaller size, structural stability, ease of production, high affinity, and low immunogenicity, among other characteristics. In this work, we describe an integrated proteomics platform for the high-throughput screening of nanobodies against different SARS-CoV-2 spike variants. To demonstrate this platform, we immunized a camel with subunit 1 (S1) of the wild-type spike protein and constructed a nanobody phage library. The binding and neutralizing activities of the nanobodies against 72 spike variants were then measured, resulting in the identification of two nanobodies (C-282 and C-39) with broad neutralizing activity against six non-Omicron variants (D614G, Alpha, Beta, Gamma, Delta, Kappa) and five Omicron variants (BA.1−5). Their neutralizing capability was validated using in vitro pseudovirus-based neutralization assays. All these results demonstrate the utility of our proteomics platform to identify new nanobodies with broad neutralizing capability and to develop a treatment for patients with SARS-CoV-2 variant infection in the future.

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Nanobody–GroEL interactions in endosymbionts of whitefly: exploration and implications for pest and disease management

Ali,

Ume-Farwa

2023

J Plant Dis Prot

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A nanobody recognizes a unique conserved epitope and potently neutralizes SARS-CoV-2 omicron variants

Cited by 5 publications

References 80 publications

Senolytic therapy alleviates physiological human brain aging and COVID-19 neuropathology

Senolytic therapy alleviates physiological human brain aging and COVID-19 neuropathology

Proteomics Platform Reveals Broad-Spectrum Nanobodies for SARS-CoV-2 Variant Neutralization

Nanobody–GroEL interactions in endosymbionts of whitefly: exploration and implications for pest and disease management

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