Evidence map›Paper›PMID 23217195›Full record

ArticleRetrovirology2012

A bivalent recombinant protein inactivates HIV-1 by targeting the gp41 prehairpin fusion intermediate induced by CD4 D1D2 domains.

Lu Lu, Chungen Pan, Yuan Li, Hong Lu, Wu He, Shibo Jiang

Open access · goldAbstract read
In one paragraph

Article in Retrovirology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
2.5field-weighted citation impact, top 10% 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

43 citing papers in PubMed, 64 citations in OpenAlex.

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  9. Virus Entry Inhibitors: Past, Present, and Future.Advances in experimental medicine and biology · 2022
    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

6 authors at 3 institutions in 2 countries.

Lu LuKey Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College, Institute of Medical Microbiology, Fudan University, Shanghai 200032, China.
Chungen Pan
Yuan Li
Hong Lu
Wu He
Shibo Jiang
New York Blood Center · USShanghai Medical College of Fudan University · CNSun Yat-sen University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMost currently approved anti-HIV drugs (e.g., reverse transcriptase inhibitors, protease inhibitors and fusion/entry inhibitors) must act inside or on surface of the target cell to inhibit HIV infection, but none can directly inactivate virions away from cells. Although soluble CD4 (sCD4) can inactivate laboratory-adapted HIV-1 strains, it fails to reduce the viral loads in clinical trials because of its low potency against primary isolates and tendency to enhance HIV-1 infection at low concentration. Thus, it is essential to design a better HIV inactivator with improved potency for developing new anti-HIV therapeutics that can actively attack the virus in the circulation before it attaches to and enter into the target cell.

resultsWe engineered a bivalent HIV-1 inactivator, designated 2DLT, by linking the D1D2 domain of CD4 to T1144, the next generation HIV fusion inhibitor, with a 35-mer linker. The D1D2 domain in this soluble 2DLT protein could bind to the CD4-binding site and induce the formation of the gp41 prehairpin fusion-intermediate (PFI), but showed no sCD4-mediated enhancement of HIV-1 infection. The T1144 domain in 2DLT then bound to the exposed PFI, resulting in rapid inactivation of HIV-1 virions in the absence of the target cell. Beside, 2DLT could also inhibit fusion of the virus with the target cell if the virion escapes the first attack of 2DLT.

conclusionThis bivalent molecule can serve as a dual barrier against HIV infection by first inactivating HIV-1 virions away from cells and then blocking HIV-1 entry on the target cell surface, indicating its potential for development as a new class of anti-HIV drug.

Indexed as

Amino Acid SequenceCD4 AntigensCell LineHIV-1HIV Envelope Protein gp120HIV Envelope Protein gp41HIV Fusion InhibitorsHumansMembrane FusionMolecular Sequence DataProtein BindingProtein Interaction Domains and MotifsProtein MultimerizationReceptors, CCR5Recombinant Fusion ProteinsRecombinant ProteinsCD4 AntigensHIV Envelope Protein gp120HIV Envelope Protein gp41HIV Fusion InhibitorsReceptors, CCR5Recombinant Fusion ProteinsRecombinant Proteinsrecombinant soluble CD4

Identifiers

PMID23217195
PMCPMC3531269
OpenAlexW2150854802

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.