A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2

Chi, Xiangyang; Yan, Renhong; Zhang, Jun; Zhang, Guanying; Zhang, Yuanyuan; Meng, Hao; Zhang, Zhe; Fan, Pengfei; Ya, Dong; Yang, Yating; Chen, Zhengshan; Guo, Yingying; Zhang, Jinlong; Li, Yaning; Song, Xiaohong; Chen, Yi; Xia, Lu; Fu, Ling; Hou, Lihua; Xu, Junjie; Yu, Changming; Li, Jianmin; Zhou, Qiang; Chen, Wei

doi:10.1126/science.abc6952

Cited by 1,427 publications

(1,756 citation statements)

References 69 publications

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“…We identified a potently neutralizing molecule of Nb11-59, which recognizes the wildtype and eight kinds of mutants of RBD proteins. Nb11-59 was capable of inhibiting the replication of authentic SARS-CoV-2 in vitro with ND50 of 0.55 μg/mL, which is similar to or lower than the ND50 or IC50 values of several reported mAbs isolated from human B cells 4,28,29 . Importantly, Nb11-59 herein demonstrates neutralizing abilities more than 4 fold higher than other reported Nbs, including n3130 and n3088 with IC50 of 4.0 μg/mL and 2.6 μg/mL, respectively, against authentic SARS-CoV-2 30 .…”

Section: Discussionmentioning

confidence: 51%

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A potent neutralizing nanobody against SARS-CoV-2 with inhaled delivery potential

Gai¹,

Li³

et al. 2020

Preprint

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The outbreak of COVID-19 has emerged as a global pandemic. The unprecedented scale and severity call for rapid development of effective prophylactics or therapeutics. We here reported Nanobody (Nb) phage display libraries derived from four camels immunized with the SARS-CoV-2 spike receptor-binding domain (RBD), from which 381 Nbs were identified to recognize SARS-CoV-2-RBD. Furthermore, seven Nbs were shown to block interaction of human angiotensin converting enzyme 2 (ACE2) with SARS-CoV-2-RBD-variants, bat-SL-CoV-WIV1-RBD and SARS-CoV-1-RBD. Among the seven candidates, Nb11-59 exhibited the highest activity against authentic SARS-CoV-2 with ND50 of 0.55 μg/mL. Nb11-59 can be produced on a large-scale in Pichia pastoris, with 20 g/L titer and 99.36% purity. It also showed good stability profile, and nebulization did not impact its stability. Overall, Nb11-59 might be a promising prophylactic and therapeutic molecule against COVID-19, especially through inhalation delivery.

show abstract

Section: Discussionmentioning

confidence: 51%

“…However, SARS-CoV-2 demonstrates a higher human-to-human transmissibility than SARS-CoV. Patients with confirmed SARS-CoV-2 infection had mild to severe respiratory illness with symptoms of fever, cough, headache, dyspnea and pneumonia 4 . To date, no vaccine or therapeutic has been approved to prevent or treat COVID- 19.…”

Section: Introductionmentioning

confidence: 99%

A potent neutralizing nanobody against SARS-CoV-2 with inhaled delivery potential

Gai¹,

Li³

et al. 2020

Preprint

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“…An intriguing way to tackle the SARS-CoV-2 infection is to disrupt the entrance of the virus into host cells by blocking the molecular machinery implied in this fundamental step [36,62,70,73]. The structural basis of the interaction between ACE2 and the S glycoprotein RBD (Figure 1) could drive the discovery of small molecules and monoclonal antibodies [8,52,66] able to slow down, or even prevent, the development of COVID-19 [7,27,39,74]. An ideal drug candidate should selectively target the RBD without interacting with ACE2, to avoid possible side effects linked to angiotensin physiology [43,55].…”

Section: Introductionmentioning

confidence: 99%

Supervised molecular dynamics for exploring the druggability of the SARS-CoV-2 spike protein

Deganutti

Prischi

Reynolds

2020

Preprint

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The recent outbreak of the respiratory syndrome-related coronavirus (SARS-CoV-2) is stimulating an unprecedented scientific campaign to alleviate the burden of the coronavirus disease (COVID-19). One line of research has focused on targeting SARS-CoV-2 proteins fundamental for its replication by repurposing drugs approved for other diseases. The first interaction between the virus and the host cell is mediated by the spike protein on the virus surface and the human angiotensin-converting enzyme (ACE2). Small molecules able to bind the receptor-binding domain (RBD) of the spike protein and disrupt the binding to ACE2 would offer an important tool for slowing, or even preventing, the infection. Here, we screened 2421 approved small molecules in silico and validated the docking outcomes through extensive molecular dynamics simulations. Out of six drugs characterized as putative RBD binders, the cephalosporin antibiotic cefsulodin was further assessed for its effect on the binding between the RBD and ACE2, suggesting the importance of considering the dynamic formation of the heterodimer when judging any potential candidate.

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“…In addition, three novel OGSs (T73, S161, and S221) are located in the NTD (Fig. 3a), which bind the monoclonal antibody isolated from COVID-19 patients 5 . Furthermore, two novel OGSs (S1170, S1175) are located in the HR2 region and 4 OGSs (S673, T676, S810 and S813) are proximal to S1/S2 cleavage sites (R685/R686) 16 .…”

Section: The Synthesis and Characterizations Of Wr-sio 2 Based On Tmentioning

confidence: 99%

“…Several vaccines for COVID-19 are currently being developed. Most of these vaccines target the SARS-CoV-2 spike (S) protein [3][4][5] , which is the main target of the humoral immune response. The S protein protrudes from the SARS-CoV-2 surface and consists of two subunits S1 and S2 2,6 .…”

mentioning

confidence: 99%

Comprehensive O-glycosylation analysis of the SARS-CoV-2 spike protein

Dong¹,

Chen²,

Yan³

et al. 2020

Preprint

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The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a serious public health threat. Most vaccines being developed against SARS-CoV-2 target the highly glycosylated spike protein (S). A good knowledge of the glycosylation profile of this protein is key for successful vaccine development. Unlike the 22 confirmed N-glycosylation sites (NGSs) on the SARS-CoV-2 S, only a few O-glycosylation sites (OGSs) on this protein have been reported. This difference is mainly ascribed to an extremely low O-glycosylation stoichiometry. Herein, we comprehensively analyzed the O-glycosylation profile of recombinant SARS-CoV-2 S employing biomimetic polymer consisting of Trp-Arg monomer. Twenty-six OGSs and 33 O-linked glycans (OLGs) in the SARS-CoV-2 S were unambiguously identified, among which 24 OGSs and 25 OLGs are novel to the SARS-CoV-2 S. Our study reveals the comprehensive O-glycosylation profile of the SARS-CoV-2 S, which might shed light on viral pathobiology and assist in vaccine development.

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A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2

Cited by 1,427 publications

References 69 publications

A potent neutralizing nanobody against SARS-CoV-2 with inhaled delivery potential

A potent neutralizing nanobody against SARS-CoV-2 with inhaled delivery potential

Supervised molecular dynamics for exploring the druggability of the SARS-CoV-2 spike protein

Comprehensive O-glycosylation analysis of the SARS-CoV-2 spike protein

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