Author Correction: Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with ACE2

Huo, Jiangdong; Bas, Audrey Le; Ruza, R.R.; Hme., Duyvesteyn; Mikolajek, Halina; Malinauskas, Tomas; Tan, Tiong Kit; Rijal, Pramila; Dumoux, Maud; Ward, Philip N.; Ren, Jingshan; Zhou, Daming; Harrison, Peter; Weckener, Miriam; Clare, Daniel K.; Vogirala, Vinod K.; Radecke, Julika; Moynié, L.; Zhao, Yuguang; Gilbert‐Jaramillo, Javier; Knight, Michael; Tree, Julia A.; Buttigieg, Karen; Coombes, Naomi; Elmore, Michael J.; Carroll, Miles W.; Carrique, L.; Shah, Pranav N.M.; James, William; Townsend, Alain; Stuart, D.I.; Owens, Raymond J.; Naismith, J.H.

doi:10.1038/s41594-020-00527-9

Cited by 13 publications

(7 citation statements)

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“…2 ). These sequences were distinct from the previously published sequences that also bind SARS-CoV-2 spike protein 19 – 26 . Additional reports demonstrate compelling binding to SARS-CoV-2 spike protein, yet have not disclosed nanobody sequences allowing for a direct comparison 27 – 30 .…”

Section: Resultscontrasting

confidence: 72%

“…Blue highlights indicate sequence diversity with NIH-CoVnb-112, highlighted in gray, set as the reference sequence for comparison. For comparison, seven previously reported nanobody sequences have clearly distinct sequences: Ty1 23 , VHH72 24 , H11-D4 19 , MR3 20 , Sb#14 21 , Sb23 22 , and W25UACh 25 and possess shorter CDR3 domains (represented in NIH-CoVnb-112 by amino acids 99–120). …”

Section: Resultsmentioning

confidence: 99%

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High affinity nanobodies block SARS-CoV-2 spike receptor binding domain interaction with human angiotensin converting enzyme

Esparza

Martin

Anderson

et al. 2020

Sci Rep

118

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There are currently few approved effective treatments for SARS-CoV-2, the virus responsible for the COVID-19 pandemic. Nanobodies are 12–15 kDa single-domain antibody fragments that can be delivered by inhalation and are amenable to relatively inexpensive large scale production compared to other biologicals. We have isolated nanobodies that bind to the SARS-CoV-2 spike protein receptor binding domain and block spike protein interaction with the angiotensin converting enzyme 2 (ACE2) with 1–5 nM affinity. The lead nanobody candidate, NIH-CoVnb-112, blocks SARS-CoV-2 spike pseudotyped lentivirus infection of HEK293 cells expressing human ACE2 with an EC50 of 0.3 µg/mL. NIH-CoVnb-112 retains structural integrity and potency after nebulization. Furthermore, NIH-CoVnb-112 blocks interaction between ACE2 and several high affinity variant forms of the spike protein. These nanobodies and their derivatives have therapeutic, preventative, and diagnostic potential.

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Section: Resultscontrasting

confidence: 72%

Section: Resultsmentioning

confidence: 99%

High affinity nanobodies block SARS-CoV-2 spike receptor binding domain interaction with human angiotensin converting enzyme

Esparza

Martin

Anderson

et al. 2020

Sci Rep

118

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“… 60 Another nanobody produced by a naïve llama single-domain antibody library and PCR-based maturation showed neutralizing activity against live SARS-CoV-2. 61 Our data may help direct the development of nanobodies targeting nsps for COVID-19 therapy. 31 , 44 , 45 , 62 …”

Section: Discussionmentioning

confidence: 89%

Dynamic landscape mapping of humoral immunity to SARS-CoV-2 identifies non-structural protein antibodies associated with the survival of critical COVID-19 patients

Cheng

Zhang

Chen

et al. 2021

Sig Transduct Target Ther

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A comprehensive analysis of the humoral immune response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential in understanding COVID-19 pathogenesis and developing antibody-based diagnostics and therapy. In this work, we performed a longitudinal analysis of antibody responses to SARS-CoV-2 proteins in 104 serum samples from 49 critical COVID-19 patients using a peptide-based SARS-CoV-2 proteome microarray. Our data show that the binding epitopes of IgM and IgG antibodies differ across SARS-CoV-2 proteins and even within the same protein. Moreover, most IgM and IgG epitopes are located within nonstructural proteins (nsps), which are critical in inactivating the host’s innate immune response and enabling SARS-CoV-2 replication, transcription, and polyprotein processing. IgM antibodies are associated with a good prognosis and target nsp3 and nsp5 proteases, whereas IgG antibodies are associated with high mortality and target structural proteins (Nucleocapsid, Spike, ORF3a). The epitopes targeted by antibodies in patients with a high mortality rate were further validated using an independent serum cohort (n = 56) and using global correlation mapping analysis with the clinical variables that are associated with COVID-19 severity. Our data provide fundamental insight into humoral immunity during SARS-CoV-2 infection. SARS-CoV-2 immunogenic epitopes identified in this work could also help direct antibody-based COVID-19 treatment and triage patients.

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“…Another approach is the use of chimeric nanobodies-Fc (where variable region of nanobody is fused to Fc of human immunoglobulin). Two recent reports demonstrated that neutralizing nanobodies applied at low concentration (4–18 nM) significantly reduced the number of viral plaque formation upon infection in tissue culture, by effectively binding to SARS-CoV-2 S-protein RBD (Receptor-Binding Domain) and blocking binding to ACE2 receptor (Huo et al 2020 ; Schoof et al 2020 ). Remarkably, the synthetic nanobodies are small, with potential for aerosolization, and stable to heat, making them a viable alternative for prophylactic or therapeutic anti-COVID-19 applications.…”

Section: Nanotechnology As Therapeutic Strategy Against Covid-19mentioning

confidence: 99%

Recent biotechnological advances as potential intervention strategies against COVID-19

et al. 2021

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The emerging SARS-CoV-2 viral disease (COVID-19) has caused a global health alert due to its high rate of infection and mortality in individuals with chronic cardiovascular comorbidities, in addition to generating complex clinical conditions. This has forced the scientific community to explore different strategies that allow combating this viral infection as well as treating life-threatening systemic effect of the infection on the individual. In this work, we have reviewed the most recent scientific evidence to provide a comprehensive panorama regarding the biotechnological strategies that have been proposed to combat this new viral infection. We have focused our analysis on vaccine production, nanotechnology applications, repurposing of know drugs for unrelated pathologies, and the search for bioactive molecules obtained from natural products. The goals include safely use as potential prophylactic or therapeutic treatments, based on in silico and in vivo studies, including clinical trials around the world for the correct and timely diagnosis of the infection. This review aims to highlight the development of new ideas that can decrease the time lines for research output and improve research quality while at the same time, keeping in mind the efficacy and safety aspects of these potential biotechnological strategies.

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Author Correction: Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with ACE2

Abstract: In the version of this article initially published online, in Table 1, the PDB accession code for the S20G 2PF cryo-EM structure was incorrect. The correct accession code is PDB 6ZRQ. The error has been corrected in the print, PDF and HTML versions of the article.

Cited by 13 publications

References 0 publications

High affinity nanobodies block SARS-CoV-2 spike receptor binding domain interaction with human angiotensin converting enzyme

High affinity nanobodies block SARS-CoV-2 spike receptor binding domain interaction with human angiotensin converting enzyme

Dynamic landscape mapping of humoral immunity to SARS-CoV-2 identifies non-structural protein antibodies associated with the survival of critical COVID-19 patients

Recent biotechnological advances as potential intervention strategies against COVID-19

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