Related Experiment Video
Updated: Jun 21, 2026
Arbovirus Infections As Screening Tools for the Identification of Viral Immunomodulators and Host Antiviral Factors
Published on: September 13, 2018
Mechanistic Insights into PRRSV Inhibition through CD163-SRCR5 Blockade by PRRSV/CD163-IN-1
Prawit Thitayanuwat1, Kowit Hengphasatporn2, Surang Chankhamhaengdecha1
1Department of Biology, Faculty of Science, Mahidol University, Rama VI Road, Rachadhavi, Bangkok 10400, Thailand.
Abstract:
Porcine reproductive and respiratory syndrome virus (PRRSV) causes severe economic losses in the swine industry by targeting pulmonary alveolar macrophages via the CD163 receptor, particularly its SRCR5 domain. However, the molecular details of small-molecule inhibition at this interface remain unclear. Here, we provide the first mechanistic insights into how the PRRSV/CD163-IN-1 (B7) compound blocks CD163-SRCR5. Using structural refinement, molecular dynamics (MD) simulations, ensemble docking, and fragment molecular orbital (FMO) calculations, we identified a plausible B7/CD163-SRCR5 binding conformation. Due to the limitations of the crystal structure in representing conformational flexibility, we proposed an MD-refined model of CD163-SRCR5 to facilitate the efficient virtual screening of a small-molecule repurposing library. Baicalin emerged as a top candidate through the in silico analyses, consistent with previous experimental evidence. This result supports baicalin's antiviral activity, reinforcing its potential as a lead compound. This study provides a molecular basis for ligand recognition at CD163-SRCR5 and a framework for designing PRRSV entry inhibitors.
Insights
This study reveals how a compound blocks the Porcine reproductive and respiratory syndrome virus (PRRSV) from infecting swine cells. Researchers identified baicalin as a potential antiviral lead compound for PRRSV entry inhibition.
Area of Science:
- Virology
- Structural Biology
- Computational Chemistry
Background:
- Porcine reproductive and respiratory syndrome virus (PRRSV) causes significant economic losses in the swine industry.
- PRRSV infects pulmonary alveolar macrophages by binding to the CD163 receptor, specifically its Scavenger Receptor Cysteine-Rich (SRCR) domain 5 (SRCR5).
- The precise molecular mechanisms of small-molecule inhibition at the PRRSV-CD163 interface are not fully understood.
Purpose of the Study:
- To elucidate the molecular mechanisms by which small molecules inhibit PRRSV entry via the CD163-SRCR5 interaction.
- To identify potential PRRSV entry inhibitors through computational screening.
Main Methods:
- Structural refinement and molecular dynamics (MD) simulations of the CD163-SRCR5 domain.
- Ensemble docking and fragment molecular orbital (FMO) calculations to predict binding conformations.
- Virtual screening of a small-molecule repurposing library against an MD-refined CD163-SRCR5 model.
Main Results:
- A plausible binding conformation for the PRRSV/CD163-IN-1 (B7) compound at the CD163-SRCR5 interface was identified.
- An MD-refined model of CD163-SRCR5 was developed to overcome crystal structure limitations in representing conformational flexibility.
- Baicalin was identified as a top candidate inhibitor through in silico screening, aligning with prior experimental findings.
Conclusions:
- The study provides the first mechanistic insights into PRRSV entry inhibition at the molecular level.
- Baicalin's antiviral activity is supported, reinforcing its potential as a lead compound for PRRSV therapeutics.
- A framework for designing novel PRRSV entry inhibitors targeting the CD163-SRCR5 interaction has been established.
