Related Experiment Video
Updated: Jun 24, 2026
06:02
Arbovirus Infections As Screening Tools for the Identification of Viral Immunomodulators and Host Antiviral Factors
Published on: September 13, 2018
6.9K
Identification of New Compounds against PRRSV Infection by Directly Targeting CD163
Jiaqi Zhu1, Xin He2, Denzil Bernard3
1Department of Animal Science, Institute for Systems Genomics, University of Connecticut, Storrs, Connecticut, USA.
Journal of Virology
|May 3, 2023
Summary
New small molecules effectively inhibit porcine reproductive and respiratory syndrome virus (PRRSV) by blocking its entry into host cells. This discovery offers a promising new avenue for treating PRRSV, a major threat to the global swine industry.
Area of Science:
- Virology and Immunology
- Drug Discovery and Development
Background:
- Porcine reproductive and respiratory syndrome virus (PRRSV) causes significant global economic losses in the swine industry.
- Current PRRSV vaccines offer limited cross-protection, and effective treatments are lacking.
- PRRSV utilizes the scavenger receptor CD163 as its entry receptor.
Purpose of the Study:
- To screen for small molecules that inhibit PRRSV infection by targeting the CD163 receptor.
- To identify compounds that block the interaction between PRRSV and CD163.
- To explore structure-activity relationships for optimizing antiviral compounds.
Main Methods:
- Utilized bimolecular fluorescence complementation (BiFC) assays to screen small molecules targeting the CD163 scavenger receptor cysteine-rich domain 5 (SRCR5).
- Assessed inhibition of PRRSV infection in porcine alveolar macrophages.
- Confirmed compound binding to CD163-SRCR5 using biophysical methods and performed structure-activity relationship (SAR) analysis.
Main Results:
- Identified small molecules that significantly inhibit both type 1 and type 2 PRRSV infection.
- Compounds were confirmed to physically bind to the CD163-SRCR5 domain with dissociation constants (Kd) between 28–39 μM.
- SAR analysis indicated that the morpholinosulfonyl and benzenesulfonamide moieties are crucial for antiviral activity, with potential for modification.
Conclusions:
- Developed a high-throughput screening system for identifying PRRSV inhibitors targeting CD163.
- Discovered novel small molecules with potent antiviral activity against PRRSV.
- Provided insights into molecular interactions for future development of improved PRRSV therapeutics.
