HIV-1 gp41-targeting fusion inhibitory peptides enhance the gp120-targeting protein-mediated inactivation of HIV-1 virions View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-06-21

AUTHORS

Qianqian Qi, Qian Wang, Weizao Chen, Lanying Du, Dimiter S Dimitrov, Lu Lu, Shibo Jiang

ABSTRACT

Protein- or peptide-based viral inactivators are being developed as novel antiviral drugs with improved efficacy, pharmacokinetics and toxicity profiles because they actively inactivate cell-free human immunodeficiency virus type 1 (HIV-1) virions before attachment to host cells. By contrast, most clinically used antiviral drugs must penetrate host cells to inhibit viral replication. In this study, we pre-treated HIV-1 particles with a gp120-targeting bispecific multivalent protein, 2Dm2m or 4Dm2m, in the presence or absence of the gp41-targeting HIV-1 fusion inhibitory peptides enfuvirtide (T20), T2635, or sifuvirtide (SFT). HIV-1 virions were separated from the inhibitors using PEG-6000, followed by testing of the residual infectivity of the HIV-1 virions. 2Dm2m and 4Dm2m exhibited significant inactivation activity against all HIV-1 strains tested with EC50 values at the low nanomolar level, whereas none of the gp41-targeting peptides showed inactivation activity at concentrations up to 250 nM. Notably, these three peptides significantly enhanced protein-mediated inactivation against cell-free HIV-1 virions, including HIV-1 laboratory-adapted and primary HIV-1 strains, as well as those resistant to T20 or T2635 and virions released from reactivated latently HIV-1-infected cells. These results indicate that the gp120-targeting bispecific multivalent proteins 2Dm2m and 4Dm2m have potential for further development as HIV-1 inactivator-based antiviral drugs for use in the clinic, either alone or in combination with a gp41-targeting HIV-1 fusion inhibitor such as T20, to treat patients with HIV-1 infection and AIDS. More... »

PAGES

e59

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/emi.2017.46

DOI

http://dx.doi.org/10.1038/emi.2017.46

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1086111927

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28634358


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1108", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Medical Microbiology", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Medical and Health Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Anti-HIV Agents", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Drug Discovery", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Drug Resistance, Viral", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "HIV Envelope Protein gp120", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "HIV Envelope Protein gp41", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "HIV Fusion Inhibitors", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "HIV-1", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Humans", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Peptide Fragments", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Peptides", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Protein Binding", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Virion", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Virus Inactivation", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Virus Replication", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "New York Blood Center", 
          "id": "https://www.grid.ac/institutes/grid.250415.7", 
          "name": [
            "Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032, China.", 
            "Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Qi", 
        "givenName": "Qianqian", 
        "id": "sg:person.01312131175.40", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01312131175.40"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Fudan University", 
          "id": "https://www.grid.ac/institutes/grid.8547.e", 
          "name": [
            "Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032, China."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Wang", 
        "givenName": "Qian", 
        "id": "sg:person.01354142512.08", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01354142512.08"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Center for Cancer Research", 
          "id": "https://www.grid.ac/institutes/grid.417768.b", 
          "name": [
            "Protein Interactions Section, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Chen", 
        "givenName": "Weizao", 
        "id": "sg:person.0762165246.36", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0762165246.36"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "New York Blood Center", 
          "id": "https://www.grid.ac/institutes/grid.250415.7", 
          "name": [
            "Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Du", 
        "givenName": "Lanying", 
        "id": "sg:person.01062044220.77", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01062044220.77"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Center for Cancer Research", 
          "id": "https://www.grid.ac/institutes/grid.417768.b", 
          "name": [
            "Protein Interactions Section, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Dimitrov", 
        "givenName": "Dimiter S", 
        "id": "sg:person.012247636637.59", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012247636637.59"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Fudan University", 
          "id": "https://www.grid.ac/institutes/grid.8547.e", 
          "name": [
            "Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032, China."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Lu", 
        "givenName": "Lu", 
        "id": "sg:person.01364774736.90", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01364774736.90"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "New York Blood Center", 
          "id": "https://www.grid.ac/institutes/grid.250415.7", 
          "name": [
            "Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032, China.", 
            "Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA."
          ], 
          "type": "Organization"
        }, 
        "familyName": "Jiang", 
        "givenName": "Shibo", 
        "id": "sg:person.016226163047.61", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016226163047.61"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "https://doi.org/10.1073/pnas.0701478104", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1000866223"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1124/pr.58.3.10", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1004815059"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/1742-4690-7-11", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1006642600", 
          "https://doi.org/10.1186/1742-4690-7-11"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1371/journal.ppat.1004071", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1006813884"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/31514", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1007469332", 
          "https://doi.org/10.1038/31514"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/31514", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1007469332", 
          "https://doi.org/10.1038/31514"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/jvi.02566-13", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1007596718"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0092-8674(00)81430-0", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010045254"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1073/pnas.91.21.9770", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1015809885"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/jvi.05119-11", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1016519898"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/aac.48.11.4349-4359.2004", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1019483131"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1073/pnas.96.13.7496", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1020248627"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/jvi.78.22.12428-12437.2004", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1020939795"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.m800200200", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1022809864"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.antiviral.2010.08.004", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1022932744"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/jvi.77.5.2859-2865.2003", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1023939728"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/aac.46.6.1896-1905.2002", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1025555959"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0092-8674(00)80205-6", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026125546"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1084/jem.176.2.507", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028450010"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.3109/08820139.2012.736115", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1029832962"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/1742-4690-9-104", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1029982878", 
          "https://doi.org/10.1186/1742-4690-9-104"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1073/pnas.0805297105", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1030515338"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/jac/dku183", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1038066915"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/31405", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1038246480", 
          "https://doi.org/10.1038/31405"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/31405", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1038246480", 
          "https://doi.org/10.1038/31405"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.bbamem.2013.12.022", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1040131273"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/jvi.05331-11", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1042707301"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1371/journal.ppat.1000360", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1042748904"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.virol.2005.06.008", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048926620"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nsb1295-1075", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1049045339", 
          "https://doi.org/10.1038/nsb1295-1075"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/1471-2334-1-17", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1049705467", 
          "https://doi.org/10.1186/1471-2334-1-17"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.m113.484154", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1050805101"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/bi00859a010", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1055191349"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.2174/1381612043384466", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1069165229"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1082375677", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1082805979", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1083225754", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1083288845", 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2017-06-21", 
    "datePublishedReg": "2017-06-21", 
    "description": "Protein- or peptide-based viral inactivators are being developed as novel antiviral drugs with improved efficacy, pharmacokinetics and toxicity profiles because they actively inactivate cell-free human immunodeficiency virus type 1 (HIV-1) virions before attachment to host cells. By contrast, most clinically used antiviral drugs must penetrate host cells to inhibit viral replication. In this study, we pre-treated HIV-1 particles with a gp120-targeting bispecific multivalent protein, 2Dm2m or 4Dm2m, in the presence or absence of the gp41-targeting HIV-1 fusion inhibitory peptides enfuvirtide (T20), T2635, or sifuvirtide (SFT). HIV-1 virions were separated from the inhibitors using PEG-6000, followed by testing of the residual infectivity of the HIV-1 virions. 2Dm2m and 4Dm2m exhibited significant inactivation activity against all HIV-1 strains tested with EC50 values at the low nanomolar level, whereas none of the gp41-targeting peptides showed inactivation activity at concentrations up to 250\u2009nM. Notably, these three peptides significantly enhanced protein-mediated inactivation against cell-free HIV-1 virions, including HIV-1 laboratory-adapted and primary HIV-1 strains, as well as those resistant to T20 or T2635 and virions released from reactivated latently HIV-1-infected cells. These results indicate that the gp120-targeting bispecific multivalent proteins 2Dm2m and 4Dm2m have potential for further development as HIV-1 inactivator-based antiviral drugs for use in the clinic, either alone or in combination with a gp41-targeting HIV-1 fusion inhibitor such as T20, to treat patients with HIV-1 infection and AIDS.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1038/emi.2017.46", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": true, 
    "isFundedItemOf": [
      {
        "id": "sg:grant.2686869", 
        "type": "MonetaryGrant"
      }
    ], 
    "isPartOf": [
      {
        "id": "sg:journal.1047596", 
        "issn": [
          "2222-1751"
        ], 
        "name": "Emerging Microbes & Infections", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "6", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "6"
      }
    ], 
    "name": "HIV-1 gp41-targeting fusion inhibitory peptides enhance the gp120-targeting protein-mediated inactivation of HIV-1 virions", 
    "pagination": "e59", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "fe6e14c00b793cb07818039d857d4832f2b099d0f6bf1b20f85caae521f67b0d"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "28634358"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "101594885"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/emi.2017.46"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1086111927"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/emi.2017.46", 
      "https://app.dimensions.ai/details/publication/pub.1086111927"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-11T00:55", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000001_0000000264/records_8697_00000427.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "http://www.nature.com/emi/journal/v6/n6/full/emi201746a.html"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/emi.2017.46'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/emi.2017.46'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/emi.2017.46'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/emi.2017.46'


 

This table displays all metadata directly associated to this object as RDF triples.

285 TRIPLES      21 PREDICATES      78 URIs      34 LITERALS      23 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/emi.2017.46 schema:about N05b5224e1776433595d1d0cc18857fd1
2 N0666ed0301404bc4a4f439e96adee720
3 N15220295fcd049459fa1819abe4bf62f
4 N17ddf3ad3288426d805cf8d19e451b94
5 N1e7ea1f3348d4c27bffae106fcb436af
6 N206ff5c31e2f4da1a172f95b8b3dd05f
7 N2ba491612be542b3b02148011d356d50
8 N32e0d08559f34d6ca38a04e95f21a574
9 N46ceac3734d74e939167e86968e98e16
10 N49dc12194c0143238fef169aa8640935
11 N55ee49e8776247b5a97410560418f159
12 N631bb17534af463a8dc943d0814c7551
13 N69e94b54ffd946f88e55641c91275792
14 Na5f091e899f54177bd96b0c69cb2894c
15 anzsrc-for:11
16 anzsrc-for:1108
17 schema:author N436dd21b0f87488b8b17525cb4bfed8c
18 schema:citation sg:pub.10.1038/31405
19 sg:pub.10.1038/31514
20 sg:pub.10.1038/nsb1295-1075
21 sg:pub.10.1186/1471-2334-1-17
22 sg:pub.10.1186/1742-4690-7-11
23 sg:pub.10.1186/1742-4690-9-104
24 https://app.dimensions.ai/details/publication/pub.1082375677
25 https://app.dimensions.ai/details/publication/pub.1082805979
26 https://app.dimensions.ai/details/publication/pub.1083225754
27 https://app.dimensions.ai/details/publication/pub.1083288845
28 https://doi.org/10.1016/j.antiviral.2010.08.004
29 https://doi.org/10.1016/j.bbamem.2013.12.022
30 https://doi.org/10.1016/j.virol.2005.06.008
31 https://doi.org/10.1016/s0092-8674(00)80205-6
32 https://doi.org/10.1016/s0092-8674(00)81430-0
33 https://doi.org/10.1021/bi00859a010
34 https://doi.org/10.1073/pnas.0701478104
35 https://doi.org/10.1073/pnas.0805297105
36 https://doi.org/10.1073/pnas.91.21.9770
37 https://doi.org/10.1073/pnas.96.13.7496
38 https://doi.org/10.1074/jbc.m113.484154
39 https://doi.org/10.1074/jbc.m800200200
40 https://doi.org/10.1084/jem.176.2.507
41 https://doi.org/10.1093/jac/dku183
42 https://doi.org/10.1124/pr.58.3.10
43 https://doi.org/10.1128/aac.46.6.1896-1905.2002
44 https://doi.org/10.1128/aac.48.11.4349-4359.2004
45 https://doi.org/10.1128/jvi.02566-13
46 https://doi.org/10.1128/jvi.05119-11
47 https://doi.org/10.1128/jvi.05331-11
48 https://doi.org/10.1128/jvi.77.5.2859-2865.2003
49 https://doi.org/10.1128/jvi.78.22.12428-12437.2004
50 https://doi.org/10.1371/journal.ppat.1000360
51 https://doi.org/10.1371/journal.ppat.1004071
52 https://doi.org/10.2174/1381612043384466
53 https://doi.org/10.3109/08820139.2012.736115
54 schema:datePublished 2017-06-21
55 schema:datePublishedReg 2017-06-21
56 schema:description Protein- or peptide-based viral inactivators are being developed as novel antiviral drugs with improved efficacy, pharmacokinetics and toxicity profiles because they actively inactivate cell-free human immunodeficiency virus type 1 (HIV-1) virions before attachment to host cells. By contrast, most clinically used antiviral drugs must penetrate host cells to inhibit viral replication. In this study, we pre-treated HIV-1 particles with a gp120-targeting bispecific multivalent protein, 2Dm2m or 4Dm2m, in the presence or absence of the gp41-targeting HIV-1 fusion inhibitory peptides enfuvirtide (T20), T2635, or sifuvirtide (SFT). HIV-1 virions were separated from the inhibitors using PEG-6000, followed by testing of the residual infectivity of the HIV-1 virions. 2Dm2m and 4Dm2m exhibited significant inactivation activity against all HIV-1 strains tested with EC<sub>50</sub> values at the low nanomolar level, whereas none of the gp41-targeting peptides showed inactivation activity at concentrations up to 250 nM. Notably, these three peptides significantly enhanced protein-mediated inactivation against cell-free HIV-1 virions, including HIV-1 laboratory-adapted and primary HIV-1 strains, as well as those resistant to T20 or T2635 and virions released from reactivated latently HIV-1-infected cells. These results indicate that the gp120-targeting bispecific multivalent proteins 2Dm2m and 4Dm2m have potential for further development as HIV-1 inactivator-based antiviral drugs for use in the clinic, either alone or in combination with a gp41-targeting HIV-1 fusion inhibitor such as T20, to treat patients with HIV-1 infection and AIDS.
57 schema:genre research_article
58 schema:inLanguage en
59 schema:isAccessibleForFree true
60 schema:isPartOf N4f814875a824459f8c093265e42bd154
61 Nb11fff340b4845819cabfcffa6c3f384
62 sg:journal.1047596
63 schema:name HIV-1 gp41-targeting fusion inhibitory peptides enhance the gp120-targeting protein-mediated inactivation of HIV-1 virions
64 schema:pagination e59
65 schema:productId N4826fcabb563497784ae3f8248b69c02
66 N4acac3f00ace4ede9636bed02b5578e3
67 N4ade1d635e39468e902957033cfbfc32
68 N79092c8e48904a8498e4f2dcfa20e726
69 Nbabecae1063842c9acd0056c9acb3c5c
70 schema:sameAs https://app.dimensions.ai/details/publication/pub.1086111927
71 https://doi.org/10.1038/emi.2017.46
72 schema:sdDatePublished 2019-04-11T00:55
73 schema:sdLicense https://scigraph.springernature.com/explorer/license/
74 schema:sdPublisher N5d1831a8fc08443fbdbb4b46840936a4
75 schema:url http://www.nature.com/emi/journal/v6/n6/full/emi201746a.html
76 sgo:license sg:explorer/license/
77 sgo:sdDataset articles
78 rdf:type schema:ScholarlyArticle
79 N05b5224e1776433595d1d0cc18857fd1 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
80 schema:name Humans
81 rdf:type schema:DefinedTerm
82 N0666ed0301404bc4a4f439e96adee720 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
83 schema:name HIV-1
84 rdf:type schema:DefinedTerm
85 N15220295fcd049459fa1819abe4bf62f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
86 schema:name Anti-HIV Agents
87 rdf:type schema:DefinedTerm
88 N17ddf3ad3288426d805cf8d19e451b94 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
89 schema:name Virus Replication
90 rdf:type schema:DefinedTerm
91 N1e7ea1f3348d4c27bffae106fcb436af schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
92 schema:name Virion
93 rdf:type schema:DefinedTerm
94 N206ff5c31e2f4da1a172f95b8b3dd05f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
95 schema:name Drug Discovery
96 rdf:type schema:DefinedTerm
97 N2ba491612be542b3b02148011d356d50 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
98 schema:name Peptide Fragments
99 rdf:type schema:DefinedTerm
100 N32e0d08559f34d6ca38a04e95f21a574 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
101 schema:name Drug Resistance, Viral
102 rdf:type schema:DefinedTerm
103 N436dd21b0f87488b8b17525cb4bfed8c rdf:first sg:person.01312131175.40
104 rdf:rest N55f70e5aa7af44c9a48d277c16a0d5b2
105 N46ceac3734d74e939167e86968e98e16 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
106 schema:name HIV Envelope Protein gp120
107 rdf:type schema:DefinedTerm
108 N4826fcabb563497784ae3f8248b69c02 schema:name doi
109 schema:value 10.1038/emi.2017.46
110 rdf:type schema:PropertyValue
111 N49dc12194c0143238fef169aa8640935 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
112 schema:name Virus Inactivation
113 rdf:type schema:DefinedTerm
114 N4acac3f00ace4ede9636bed02b5578e3 schema:name readcube_id
115 schema:value fe6e14c00b793cb07818039d857d4832f2b099d0f6bf1b20f85caae521f67b0d
116 rdf:type schema:PropertyValue
117 N4ade1d635e39468e902957033cfbfc32 schema:name nlm_unique_id
118 schema:value 101594885
119 rdf:type schema:PropertyValue
120 N4f814875a824459f8c093265e42bd154 schema:issueNumber 6
121 rdf:type schema:PublicationIssue
122 N55ee49e8776247b5a97410560418f159 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
123 schema:name HIV Envelope Protein gp41
124 rdf:type schema:DefinedTerm
125 N55f70e5aa7af44c9a48d277c16a0d5b2 rdf:first sg:person.01354142512.08
126 rdf:rest N672b5e9650ad4e36a13e101de212b083
127 N5d1831a8fc08443fbdbb4b46840936a4 schema:name Springer Nature - SN SciGraph project
128 rdf:type schema:Organization
129 N631bb17534af463a8dc943d0814c7551 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
130 schema:name Protein Binding
131 rdf:type schema:DefinedTerm
132 N672b5e9650ad4e36a13e101de212b083 rdf:first sg:person.0762165246.36
133 rdf:rest N8c05b3a9a5ac41298948545f5505f4eb
134 N69e94b54ffd946f88e55641c91275792 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
135 schema:name Peptides
136 rdf:type schema:DefinedTerm
137 N6f56f8546f044922823bcf32f25d0fdb rdf:first sg:person.016226163047.61
138 rdf:rest rdf:nil
139 N79092c8e48904a8498e4f2dcfa20e726 schema:name dimensions_id
140 schema:value pub.1086111927
141 rdf:type schema:PropertyValue
142 N8c05b3a9a5ac41298948545f5505f4eb rdf:first sg:person.01062044220.77
143 rdf:rest N93d3b251b07f42259fac19d802a8ffba
144 N93d3b251b07f42259fac19d802a8ffba rdf:first sg:person.012247636637.59
145 rdf:rest Nd6d7144f8d4a4ea69f978231dd892e01
146 Na5f091e899f54177bd96b0c69cb2894c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
147 schema:name HIV Fusion Inhibitors
148 rdf:type schema:DefinedTerm
149 Nb11fff340b4845819cabfcffa6c3f384 schema:volumeNumber 6
150 rdf:type schema:PublicationVolume
151 Nbabecae1063842c9acd0056c9acb3c5c schema:name pubmed_id
152 schema:value 28634358
153 rdf:type schema:PropertyValue
154 Nd6d7144f8d4a4ea69f978231dd892e01 rdf:first sg:person.01364774736.90
155 rdf:rest N6f56f8546f044922823bcf32f25d0fdb
156 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
157 schema:name Medical and Health Sciences
158 rdf:type schema:DefinedTerm
159 anzsrc-for:1108 schema:inDefinedTermSet anzsrc-for:
160 schema:name Medical Microbiology
161 rdf:type schema:DefinedTerm
162 sg:grant.2686869 http://pending.schema.org/fundedItem sg:pub.10.1038/emi.2017.46
163 rdf:type schema:MonetaryGrant
164 sg:journal.1047596 schema:issn 2222-1751
165 schema:name Emerging Microbes & Infections
166 rdf:type schema:Periodical
167 sg:person.01062044220.77 schema:affiliation https://www.grid.ac/institutes/grid.250415.7
168 schema:familyName Du
169 schema:givenName Lanying
170 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01062044220.77
171 rdf:type schema:Person
172 sg:person.012247636637.59 schema:affiliation https://www.grid.ac/institutes/grid.417768.b
173 schema:familyName Dimitrov
174 schema:givenName Dimiter S
175 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012247636637.59
176 rdf:type schema:Person
177 sg:person.01312131175.40 schema:affiliation https://www.grid.ac/institutes/grid.250415.7
178 schema:familyName Qi
179 schema:givenName Qianqian
180 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01312131175.40
181 rdf:type schema:Person
182 sg:person.01354142512.08 schema:affiliation https://www.grid.ac/institutes/grid.8547.e
183 schema:familyName Wang
184 schema:givenName Qian
185 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01354142512.08
186 rdf:type schema:Person
187 sg:person.01364774736.90 schema:affiliation https://www.grid.ac/institutes/grid.8547.e
188 schema:familyName Lu
189 schema:givenName Lu
190 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01364774736.90
191 rdf:type schema:Person
192 sg:person.016226163047.61 schema:affiliation https://www.grid.ac/institutes/grid.250415.7
193 schema:familyName Jiang
194 schema:givenName Shibo
195 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016226163047.61
196 rdf:type schema:Person
197 sg:person.0762165246.36 schema:affiliation https://www.grid.ac/institutes/grid.417768.b
198 schema:familyName Chen
199 schema:givenName Weizao
200 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0762165246.36
201 rdf:type schema:Person
202 sg:pub.10.1038/31405 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038246480
203 https://doi.org/10.1038/31405
204 rdf:type schema:CreativeWork
205 sg:pub.10.1038/31514 schema:sameAs https://app.dimensions.ai/details/publication/pub.1007469332
206 https://doi.org/10.1038/31514
207 rdf:type schema:CreativeWork
208 sg:pub.10.1038/nsb1295-1075 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049045339
209 https://doi.org/10.1038/nsb1295-1075
210 rdf:type schema:CreativeWork
211 sg:pub.10.1186/1471-2334-1-17 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049705467
212 https://doi.org/10.1186/1471-2334-1-17
213 rdf:type schema:CreativeWork
214 sg:pub.10.1186/1742-4690-7-11 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006642600
215 https://doi.org/10.1186/1742-4690-7-11
216 rdf:type schema:CreativeWork
217 sg:pub.10.1186/1742-4690-9-104 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029982878
218 https://doi.org/10.1186/1742-4690-9-104
219 rdf:type schema:CreativeWork
220 https://app.dimensions.ai/details/publication/pub.1082375677 schema:CreativeWork
221 https://app.dimensions.ai/details/publication/pub.1082805979 schema:CreativeWork
222 https://app.dimensions.ai/details/publication/pub.1083225754 schema:CreativeWork
223 https://app.dimensions.ai/details/publication/pub.1083288845 schema:CreativeWork
224 https://doi.org/10.1016/j.antiviral.2010.08.004 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022932744
225 rdf:type schema:CreativeWork
226 https://doi.org/10.1016/j.bbamem.2013.12.022 schema:sameAs https://app.dimensions.ai/details/publication/pub.1040131273
227 rdf:type schema:CreativeWork
228 https://doi.org/10.1016/j.virol.2005.06.008 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048926620
229 rdf:type schema:CreativeWork
230 https://doi.org/10.1016/s0092-8674(00)80205-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026125546
231 rdf:type schema:CreativeWork
232 https://doi.org/10.1016/s0092-8674(00)81430-0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010045254
233 rdf:type schema:CreativeWork
234 https://doi.org/10.1021/bi00859a010 schema:sameAs https://app.dimensions.ai/details/publication/pub.1055191349
235 rdf:type schema:CreativeWork
236 https://doi.org/10.1073/pnas.0701478104 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000866223
237 rdf:type schema:CreativeWork
238 https://doi.org/10.1073/pnas.0805297105 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030515338
239 rdf:type schema:CreativeWork
240 https://doi.org/10.1073/pnas.91.21.9770 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015809885
241 rdf:type schema:CreativeWork
242 https://doi.org/10.1073/pnas.96.13.7496 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020248627
243 rdf:type schema:CreativeWork
244 https://doi.org/10.1074/jbc.m113.484154 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050805101
245 rdf:type schema:CreativeWork
246 https://doi.org/10.1074/jbc.m800200200 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022809864
247 rdf:type schema:CreativeWork
248 https://doi.org/10.1084/jem.176.2.507 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028450010
249 rdf:type schema:CreativeWork
250 https://doi.org/10.1093/jac/dku183 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038066915
251 rdf:type schema:CreativeWork
252 https://doi.org/10.1124/pr.58.3.10 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004815059
253 rdf:type schema:CreativeWork
254 https://doi.org/10.1128/aac.46.6.1896-1905.2002 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025555959
255 rdf:type schema:CreativeWork
256 https://doi.org/10.1128/aac.48.11.4349-4359.2004 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019483131
257 rdf:type schema:CreativeWork
258 https://doi.org/10.1128/jvi.02566-13 schema:sameAs https://app.dimensions.ai/details/publication/pub.1007596718
259 rdf:type schema:CreativeWork
260 https://doi.org/10.1128/jvi.05119-11 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016519898
261 rdf:type schema:CreativeWork
262 https://doi.org/10.1128/jvi.05331-11 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042707301
263 rdf:type schema:CreativeWork
264 https://doi.org/10.1128/jvi.77.5.2859-2865.2003 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023939728
265 rdf:type schema:CreativeWork
266 https://doi.org/10.1128/jvi.78.22.12428-12437.2004 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020939795
267 rdf:type schema:CreativeWork
268 https://doi.org/10.1371/journal.ppat.1000360 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042748904
269 rdf:type schema:CreativeWork
270 https://doi.org/10.1371/journal.ppat.1004071 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006813884
271 rdf:type schema:CreativeWork
272 https://doi.org/10.2174/1381612043384466 schema:sameAs https://app.dimensions.ai/details/publication/pub.1069165229
273 rdf:type schema:CreativeWork
274 https://doi.org/10.3109/08820139.2012.736115 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029832962
275 rdf:type schema:CreativeWork
276 https://www.grid.ac/institutes/grid.250415.7 schema:alternateName New York Blood Center
277 schema:name Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032, China.
278 Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA.
279 rdf:type schema:Organization
280 https://www.grid.ac/institutes/grid.417768.b schema:alternateName Center for Cancer Research
281 schema:name Protein Interactions Section, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.
282 rdf:type schema:Organization
283 https://www.grid.ac/institutes/grid.8547.e schema:alternateName Fudan University
284 schema:name Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032, China.
285 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...