Evidence map›Paper›PMID 29746833›Full record

ArticleCell host & microbe2018

Rational Engineering and Characterization of an mAb that Neutralizes Zika Virus by Targeting a Mutationally Constrained Quaternary Epitope.

Kannan Tharakaraman, Satoru Watanabe, Kuan Rong Chan, Jia Huan, Vidya Subramanian, Yok Hian Chionh, Aditya Raguram, Devin Quinlan, Megan McBee, Eugenia Z Ong and 8 more

Open access · bronzeAbstract read
In one paragraph

Article in Cell host & microbe, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
3.7field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
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  5. Learned features of antibody-antigen binding affinity.Frontiers in molecular biosciences · 2023
    Article
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  9. Review
  10. Glycans in Virus-Host Interactions: A Structural Perspective.Frontiers in molecular biosciences · 2021
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 5 institutions in 2 countries.

Kannan TharakaramanDepartment of Biological Engineering, Koch Institute of Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Satoru WatanabeProgram in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore.
Kuan Rong ChanProgram in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore.
Jia HuanSchool of Biological Sciences and Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.
Vidya SubramanianDepartment of Biological Engineering, Koch Institute of Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Yok Hian ChionhInfectious Diseases Interdisciplinary Research Group, Singapore-MIT Alliance for Research & Technology, Singapore, Singapore.
Aditya RaguramHarvard College, Harvard University, Cambridge, MA 02138, USA.
Devin QuinlanDepartment of Biological Engineering, Koch Institute of Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Megan McBeeInfectious Diseases Interdisciplinary Research Group, Singapore-MIT Alliance for Research & Technology, Singapore, Singapore.
Eugenia Z OngProgram in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore.
Esther S GanProgram in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore.
Hwee Cheng TanProgram in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore.
Anu TyagiSchool of Biological Sciences and Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.
Shashi BhushanSchool of Biological Sciences and Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.
Julien LescarSchool of Biological Sciences and Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.
Subhash G VasudevanProgram in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore.
Eng Eong OoiProgram in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore; Infectious Diseases Interdisciplinary Research Group, Singapore-MIT Alliance for Research & Technology, Singapore, Singapore. Electronic address: engeong.ooi@duke-nus.edu.
Ram SasisekharanDepartment of Biological Engineering, Koch Institute of Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Infectious Diseases Interdisciplinary Research Group, Singapore-MIT Alliance for Research & Technology, Singapore, Singapore. Electronic address: rams@mit.edu.
Duke-NUS Medical School · SGNanyang Technological University · SGMassachusetts Institute of Technology · USSingapore-MIT Alliance for Research and Technology · SGHarvard University Press · US

Funding

TRAINING GRANTS IN ENVIROMENTAL TOXICOLOGYT32ES007020 · NIEHS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI ESSIGMANN, JOHN M · 1985 to 2024
$13.1M
Structure-Function Relationship of GlycosaminoglycansR37GM057073 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI SASISEKHARAN, RAM · 2010 to 2019
$3.9M
Characterization and Development of a Cross Spectrum Anti-Dengue AntibodyR01AI111395 · NIAID · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI SASISEKHARAN, RAM · 2014 to 2018
$3.8M
Sequence Analysis of GlycosaminoglycansR01GM057073 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI SASISEKHARAN, RAM · 1998 to 2010
$3.1M
NIAID NIH HHS R01 AI111395NIEHS NIH HHS T32 ES007020NIGMS NIH HHS R01 GM057073NIGMS NIH HHS R37 GM057073
6 · The paper itself

Abstract

Following the recent emergence of Zika virus (ZIKV), many murine and human neutralizing anti-ZIKV antibodies have been reported. Given the risk of virus escape mutants, engineering antibodies that target mutationally constrained epitopes with therapeutically relevant potencies can be valuable for combating future outbreaks. Here, we applied computational methods to engineer an antibody, ZAb_FLEP, that targets a highly networked and therefore mutationally constrained surface formed by the envelope protein dimer. ZAb_FLEP neutralized a breadth of ZIKV strains and protected mice in distinct in vivo models, including resolving vertical transmission and fetal mortality in infected pregnant mice. Serial passaging of ZIKV in the presence of ZAb_FLEP failed to generate viral escape mutants, suggesting that its epitope is indeed mutationally constrained. A single-particle cryo-EM reconstruction of the Fab-ZIKV complex validated the structural model and revealed insights into ZAb_FLEP's neutralization mechanism. ZAb_FLEP has potential as a therapeutic in future outbreaks.

Indexed as

Protein EngineeringAnimalsAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralDengue VirusDisease Models, AnimalEpitopesFemaleMaleMiceModels, MolecularNeutralization TestsPregnancyProtein Structure, QuaternaryTreatment OutcomeAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralEpitopesViral Envelope Proteinsantibodycryo-EMefficacyflavivirusneutralizationquaternary epitopestructuretherapeuticZika virusZIKV

Identifiers

PMID29746833
PMCPMC6018055
OpenAlexW2801574648

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.