PLpro Protein Inhibitor Compounds for Viral Replication Control
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Solution Overview
Problem
Current antiviral strategies lack effective inhibitors for PLpro, a key protease involved in viral replication and host cell control, which can lead to immune escape and increased viral load.
Innovation Solution
Development of a PLPro protein inhibitor compound with specific structural features, including substituted naphthyl and aryl groups, to target and inhibit PLpro activity, thereby reducing viral load and restoring the host's innate immune system.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current antiviral strategies are used, then viral replication continues unchecked, but no effective PLpro inhibition is achieved
Solution Approach 1:
The patent employs parameter changes by systematically modifying molecular structures (changing chemical parameters) to develop compounds with optimized PLpro inhibition activity. The general chemical formula encompasses multiple variants with different substituents, allowing optimization of binding affinity and selectivity parameters to achieve effective viral replication inhibition.
2Productivity
If PLpro activity is not inhibited, then viral load increases and immune escape occurs, but host innate immune system remains suppressed
Solution Approach 1:
The patent applies preliminary anti-action by developing PLpro inhibitors that prevent the protease from cleaving ubiquitin and ISG15 modifications before immune escape can occur. The compound interferes with PLpro's catalytic activity in advance, blocking the pathway that leads to immune suppression and allowing the host's innate immune system to remain functional.
3Reliability
If a specific PLpro inhibitor compound is developed, then PLpro activity is inhibited and viral replication is reduced, but the compound structure becomes complex with multiple substituents
Solution Approach 1:
The patent applies segmentation by dividing the molecule into distinct functional segments: a core structure and multiple substituent positions (Ar1, Ar2, B, W1, W2, W4, R1-R23, L1-L6). This modular approach allows systematic optimization of each segment's contribution to PLpro binding while maintaining an organized, analyzable molecular architecture.
Solution Approach 2:
The patent implements local quality by assigning specific functional properties to different regions of the molecule. Different substituents at specific positions provide localized functions such as hydrogen bonding, hydrophobic interactions, or electrostatic interactions with complementary residues in the PLpro active site, optimizing overall inhibition effectiveness.
Data Source
AI summary
Disclosed in the present invention are a PLpro protease inhibitor, and a preparation method and application thereof. The PLpro protease inhibitor can be combined with one or more pharmaceutically acceptable auxiliary materials or one or more other active ingredients to serve as a PLpro inhibitor to treat diseases caused by or diseases related to virus infection. The auxiliary material can be a carrier, a diluent, an adhesive, a lubricant, a wetting agent, etc. The protease inhibitor has high inhibitory activity, and can be used for broad-spectrum antivirals, especially for coronaviruses, for example, HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU, SARS-CoV, MERS-CoV, SARS-CoV-2, etc., in particular SARS-CoV, MERS-CoV, SARS-CoV-2.