Evidence map›Paper›PMID 32727587›Full record

ArticleVirology journal2020

Small molecules block the interaction between porcine reproductive and respiratory syndrome virus and CD163 receptor and the infection of pig cells.

Chang Huang, Denzil Bernard, Jiaqi Zhu, Radha Charan Dash, Alexander Chu, Alec Knupp, Anna Hakey, M Kyle Hadden, Antonio Garmendia, Young Tang

Open access · goldAbstract read
In one paragraph

Article in Virology journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
4.3field-weighted citation impact, top 5% 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

29 citing papers in PubMed, 50 citations in OpenAlex.

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  9. Small Molecule Inhibitors ofInternational journal of molecular sciences · 2024
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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

10 authors at 2 institutions in 1 country.

Chang HuangDepartment of Animal Science, Institute for Systems Genomics, University of Connecticut, 1390 Storrs Rd, Storrs, CT, 06269, USA.
Denzil BernardAtomwise Inc, 717 Market Street, Suite 800, San Francisco, CA, 94103, USA.
Jiaqi ZhuDepartment of Animal Science, Institute for Systems Genomics, University of Connecticut, 1390 Storrs Rd, Storrs, CT, 06269, USA.
Radha Charan DashDepartment of Pharmaceutical Sciences, University of Connecticut, 69 North Eagleville Rd, Storrs, CT, 06029, USA.
Alexander ChuDepartment of Animal Science, Institute for Systems Genomics, University of Connecticut, 1390 Storrs Rd, Storrs, CT, 06269, USA.
Alec KnuppDepartment of Animal Science, Institute for Systems Genomics, University of Connecticut, 1390 Storrs Rd, Storrs, CT, 06269, USA.
Anna HakeyDepartment of Animal Science, Institute for Systems Genomics, University of Connecticut, 1390 Storrs Rd, Storrs, CT, 06269, USA.
M Kyle HaddenDepartment of Pharmaceutical Sciences, University of Connecticut, 69 North Eagleville Rd, Storrs, CT, 06029, USA.
Antonio GarmendiaDepartment of Pathobiology and Veterinary Sciences, University of Connecticut, 61 North Eagleville Road, Storrs, CT, 06269, USA. antonio.garmendia@uconn.edu.
Young TangDepartment of Animal Science, Institute for Systems Genomics, University of Connecticut, 1390 Storrs Rd, Storrs, CT, 06269, USA. yong.tang@uconn.edu.ORCID 0000-0001-6188-7758
University of Connecticut · USHealthwise · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPorcine reproductive and respiratory syndrome (PRRS) is one of the most economically devastating diseases affecting the pork industry globally. PRRS is caused by PRRS virus (PRRSV). Currently there are no effective treatments against this swine disease.

methodsThrough artificial intelligence molecular screening, we obtained a set of small molecule compounds predicted to target the scavenger receptor cysteine-rich domain 5 (SRCR5) of CD163, which is a cell surface receptor specific for PRRSV infection. These compounds were screened using a cell-based bimolecular fluorescence complementation (BiFC) assay, and the function of positive hit was further evaluated and validated by PRRSV-infection assay using porcine alveolar macrophages (PAMs).

resultsUsing the BiFC assay, we identified one compound with previously unverified function, 4-Fluoro-2-methyl-N-[3-(3-morpholin-4-ylsulfonylanilino)quinoxalin-2-yl]benzenesulfonamide (designated here as B7), that significantly inhibits the interaction between the PRRSV glycoprotein (GP2a or GP4) and the CD163-SRCR5 domain. We further demonstrated that compound B7 inhibits PRRSV infection of PAMs, the primary target of PRRSV in a dose-dependent manner. B7 significantly inhibited the infection caused by both type I and type II PRRSV strains. Further comparison and functional evaluation of chemical compounds structurally related to B7 revealed that the 3-(morpholinosulfonyl)aniline moiety of B7 or the 3-(piperidinylsulfonyl)aniline moiety in a B7 analogue is important for the inhibitory function against PRRSV infection.

conclusionsOur study identified a novel strategy to potentially prevent PRRSV infection in pigs by blocking the PRRSV-CD163 interaction with small molecules.

Indexed as

AnimalsAntigens, CDAntigens, Differentiation, MyelomonocyticArtificial IntelligenceCD163 AntigenCell LineHEK293 CellsHumansMacrophages, AlveolarPorcine respiratory and reproductive syndrome virusProtein DomainsReceptors, Cell SurfaceSmall Molecule LibrariesSwineAntigens, CDAntigens, Differentiation, MyelomonocyticCD163 AntigenReceptors, Cell SurfaceSmall Molecule LibrariesBimolecular fluorescence complementation (BiFC)CD163Porcine alveolar macrophages (PAMs)Porcine reproductive and respiratory syndrome (PRRS)Protein-protein interaction (PPI)PRRS viruses (PRRSV)Scavenger receptor cysteine-rich domain 5 (SRCR5)

Identifiers

PMID32727587
PMCPMC7392821
OpenAlexW3045984515

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.