Evidence map›Paper›PMID 31749796›Full record

ArticleFrontiers in immunology2019

Enhanced Antiviral Activity of Human Surfactant Protein D by Site-Specific Engineering of the Carbohydrate Recognition Domain.

Martin van Eijk, Marine L B Hillaire, Guus F Rimmelzwaan, Michael J Rynkiewicz, Mitchell R White, Kevan L Hartshorn, Martin Hessing, Peter A Koolmees, Monique H Tersteeg, Maarten H van Es and 3 more

Abstract read
In one paragraph

Article in Frontiers in immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
–field-weighted citation impact
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

12 citing papers in PubMed.

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  12. Innate Immunity and Influenza A Virus Pathogenesis: Lessons for COVID-19.Frontiers in cellular and infection microbiology · 2020
    Review
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

13 authors.

Martin van EijkDivision of Molecular Host Defence, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands.
Marine L B HillaireDepartment of Viroscience, Erasmus MC, Rotterdam, Netherlands.
Guus F RimmelzwaanResearch Center for Emerging Infections and Zoonoses, University of Veterinary Medicine, Hanover, Germany.
Michael J RynkiewiczDepartment of Physiology and Biophysics, Boston University School of Medicine, Boston, MA, United States.
Mitchell R WhiteDepartment of Medicine, Boston University School of Medicine, Boston, MA, United States.
Kevan L HartshornDepartment of Medicine, Boston University School of Medicine, Boston, MA, United States.
Martin HessingU-Protein Express B.V., Life Science Incubator, Utrecht, Netherlands.
Peter A KoolmeesDivision of Veterinary Public Health, Faculty of Veterinary Medicine, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, Netherlands.
Monique H TersteegDivision of Veterinary Public Health, Faculty of Veterinary Medicine, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, Netherlands.
Maarten H van EsNOMI, Optomechatronics, TNO, Delft, Netherlands.
Tjarko MeijerhofDepartment of Medical Microbiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Anke HuckriedeDepartment of Medical Microbiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Henk P HaagsmanDivision of Molecular Host Defence, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Innate immunity is critical in the early containment of influenza A virus (IAV) infection and surfactant protein D (SP-D) plays a crucial role in innate defense against IAV in the lungs. Multivalent lectin-mediated interactions of SP-D with IAVs result in viral aggregation, reduced epithelial infection, and enhanced IAV clearance by phagocytic cells. Previous studies showed that porcine SP-D (pSP-D) exhibits distinct antiviral activity against IAV as compared to human SP-D (hSP-D), mainly due to key residues in the lectin domain of pSP-D that contribute to its profound neutralizing activity. These observations provided the basis for the design of a full-length recombinant mutant form of hSP-D, designated as "improved SP-D" (iSP-D). Inspired by pSP-D, the lectin domain of iSP-D has 5 amino acids replaced (Asp324Asn, Asp330Asn, Val251Glu, Lys287Gln, Glu289Lys) and 3 amino acids inserted (326Gly-Ser-Ser). Characterization of iSP-D revealed no major differences in protein assembly and saccharide binding selectivity as compared to hSP-D. However, hemagglutination inhibition measurements showed that iSP-D expressed strongly enhanced activity compared to hSP-D against 31 different IAV strains tested, including (pandemic) IAVs that were resistant for neutralization by hSP-D. Furthermore, iSP-D showed increased viral aggregation and enhanced protection of MDCK cells against infection by IAV. Importantly, prophylactic or therapeutic application of iSP-D decreased weight loss and reduced viral lung titers in a murine model of IAV infection using a clinical isolate of H1N1pdm09 virus. These studies demonstrate the potential of iSP-D as a novel human-based antiviral inhalation drug that may provide immediate protection against or recovery from respiratory (pandemic) IAV infections in humans.

Indexed as

CarbohydratesProtein EngineeringProtein Interaction Domains and MotifsBinding SitesDisease ResistanceGlycosylationHumansInfluenza A virusInfluenza, HumanModels, MolecularMolecular ConformationProtein BindingPulmonary Surfactant-Associated Protein DRecombinant ProteinsStructure-Activity RelationshipCarbohydratesPulmonary Surfactant-Associated Protein DRecombinant Proteinsantiviral agentcollectininfluenza A virusinnate immunitylung infectionpandemicsrecombinant expressionsurfactant protein D

Identifiers

PMID31749796
PMCPMC6842947

What OpenQuestion holds

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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.