A human monoclonal antibody blocking SARS-CoV-2 infection

Wang, Chunyan; Li, Wentao; Drabek, Dubravka; Okba, Nisreen M.A.; Haperen, Rien van; Osterhaus, Albert D. M. E.; Kuppeveld, Frank J. M. van; Haagmans, Bart L.; Grosveld, Frank; Bosch, Berend Jan

doi:10.1038/s41467-020-16256-y

Cited by 1,057 publications

(1,038 citation statements)

References 24 publications

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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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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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“…Scientific studies of the nAbs to SARS, MERS on animal models proved their protection effect. Currently researchers all over the world are racing to isolated nAbs from Covid-19 immunized animals (llama) 35 , available SAR-Cov-1 neutralizing antibody 36 and/or human B cells of infected patients 37 to develop potential therapeutics.…”

Section: Fig8 Competition Facs Evaluation Of Neutralizing Potentialsmentioning

confidence: 99%

Isolation of and Characterization of Neutralizing Antibodies to Covid-19 from a Large Human Naïve scFv Phage Display Library

Aq¹,

Zhao²,

Bai³

et al. 2020

Preprint

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SARS has caused currently ongoing global plague and imposed great challenges to health managing systems all over the world, with millions of infections and hundreds of thousands of deaths. In addition to racing to develop vaccines, neutralizing antibodies (nAbs) to this virus have been extensively sought and are expected to provide another prevention and therapy tool against this frantic pandemic. To offer fast isolation and shortened early development, a large human naïve phage display antibody library, was built and used to screen specific nAbs to the receptor-binding domain, RBD, the key for Covid-19 virus entry through a human receptor, ACE2. The obtained RBD-specific antibodies were characterized by epitope mapping, FACS and neutralization assay. Some of the antibodies demonstrated spike-neutralizing property and ACE2-competitiveness. Our work proved that RBD-specific neutralizing binders from human naïve antibody phage display library are promising candidates to for further Covid-19 therapeutics development.

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“…Monoclonal antibodies targeting RBD are under consideration as SARS-CoV-2 therapeutics 24 . We screened 13 different commercially available monoclonal SARS-CoV-2 Spike RBD antibodies with the SARS-CoV-2 biosensor ( Fig.…”

Section: The Sars-cov-2 Biosensor Is Sensitive To Neutralizing Antibomentioning

confidence: 99%

Nanoluciferase complementation-based biosensor reveals the importance of N- linked glycosylation of SARS-CoV-2 Spike for viral entry

Azad

Singaravelu

Taha

et al. 2020

Preprint

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The ongoing COVID-19 pandemic has highlighted the` immediate need for the development of antiviral therapeutics targeting different stages of the SARS-CoV-2 lifecycle. We developed a bioluminescence-based biosensor to interrogate the interaction between the SARS-CoV-2 viral spike protein and its host entry receptor, angiotensin-converting enzyme 2 (ACE2). The biosensor assay is based on a Nanoluciferase complementation reporter, composed of two subunits, Large BiT and Small BiT, fused to the spike receptor-binding domain (RBD) of the SARS-CoV-2 S protein and ACE2 ectodomain, respectively. Using this biosensor, we uncovered a critical role for glycosylation of asparagine residues within the RBD in mediating successful binding to the cellular ACE2 receptor and subsequent virus infection. Our findings support RBD glycosylation as a therapeutic and vaccine target to blunt SARSCoV- 2 infections.

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A human monoclonal antibody blocking SARS-CoV-2 infection

Cited by 1,057 publications

References 24 publications

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

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

Isolation of and Characterization of Neutralizing Antibodies to Covid-19 from a Large Human Naïve scFv Phage Display Library

Nanoluciferase complementation-based biosensor reveals the importance of N- linked glycosylation of SARS-CoV-2 Spike for viral entry

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