PRRSV Entry Inhibitors Targeting the CD163-SRCR5 Receptor

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Solution Overview

Problem

There is a need for effective treatments against porcine reproductive and respiratory syndrome (PRRS) caused by PRRSV, as current vaccines are not broadly effective due to the virus's high genetic and antigenic heterogeneity, and existing small molecules do not target the protein-protein interactions between PRRSV and the CD163-SRCR5 domain.

Innovation Solution

Development of small molecule compounds, such as 4-fluoro-2-methyl-N-[3-(3-morpholin-4-ylsulfonylanilino)quinoxalin-2-yl]benzenesulfonamide (B7), which inhibit the interaction between PRRSV glycoproteins and the CD163-SRCR5 domain by artificial intelligence molecular screening and BiFC assays, reducing viral infection in porcine alveolar macrophages.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current vaccines are used to prevent PRRS, then some protection is provided, but broad effectiveness is lacking due to high genetic and antigenic heterogeneity of PRRSV

Engineering Contradiction:

Improvevaccine effectivenessVSAvoidbroad protection against PRRSV strains

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent extracts and targets the specific CD163-SRCR5 domain, which is a conserved receptor structure that all PRRSV strains must interact with for infection. By focusing on this essential, conserved region rather than variable viral antigens, the approach achieves broad effectiveness across different PRRSV strains while maintaining reliable protection.

Inventive Principle:

Principle #2Taking out (Extraction)

2Reliability

If small molecules are developed to block PRRSV-CD163 interaction, then viral entry can be inhibited, but no such molecules have been reported targeting this specific protein-protein interaction

Engineering Contradiction:

Improveviral entry inhibitionVSAvoidavailability of targeting compounds

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent introduces small molecule compounds as intermediary substances that bind to the CD163-SRCR5 domain and block the protein-protein interaction between CD163 and PRRSV glycoproteins. These intermediary molecules physically interfere with the viral entry mechanism without requiring genetic modification or complex biological systems, enabling reliable inhibition of viral entry.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Reliability

If the CD163-SRCR5 domain is targeted to prevent PRRSV infection, then viral entry is blocked, but the structural complexity of the domain requires precise targeting

Engineering Contradiction:

Improveinfection preventionVSAvoidtargeting precision requirements

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies local quality by designing small molecules that specifically target the loop 5-6 region (Phe 544-Arg 570) of the CD163-SRCR5 domain, particularly focusing on the Arg 561 residue. This localized targeting approach within the larger domain structure achieves precise inhibition of PRRSV binding while maintaining reliability across different viral strains.

Inventive Principle:

Principle #3Local quality

Data Source

PatentUS12569495B2Inhibitors of porcine reproductive and respiratory syndrome virus

Publication Date: 2026.03.10 ATOMWISE INC

AI summary

Disclosed herein are compositions comprising a compound of Formula (I) and methods for treating or prophylaxis of porcine reproductive and respiratory syndrome (PRRS) therewith (I).