HCMV Pentamer Modulators for Host Receptor Entry Blocking

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Solution Overview

Problem

Current vaccines and treatments for human cytomegalovirus (HCMV) show modest efficacy in preventing infection, and there is a need for effective therapeutics that target the early steps of the HCMV infection cycle, particularly the interaction between the gH/gL/UL128-131A pentamer and host cell proteins to inhibit viral entry.

Innovation Solution

Identification of modulators that interfere with the binding of the HCMV gH/gL/UL128-131A pentamer to host cell proteins such as beta-2-microglobulin (B2M), neuropilin 2 (NRP2), and thrombomodulin (THBD) by targeting specific residues, using antibodies, peptides, or small molecules to decrease viral entry and infection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current vaccines and treatments are used, then HCMV infection prevention is attempted, but efficacy is only modest

Engineering Contradiction:

Improveefficacy of HCMV preventionVSAvoidprotection against viral infection

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent extracts and targets specific host cell proteins (B2M, NRP2, THBD) that are essential for HCMV entry. By identifying and blocking these specific proteins rather than using broad-spectrum approaches, the invention achieves more reliable prevention of viral infection, directly addressing the modest efficacy of current vaccines and treatments.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent uses modulators as intermediary substances that block the interaction between the HCMV gH/gL/UL128-131A pentamer and host cell proteins. These modulators act as mediators that prevent the viral entry process without requiring the virus to overcome vaccine-induced immunity, thereby improving prevention reliability.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If modulators are used to inhibit binding of gH/gL/UL128-131A pentamer to host cell proteins, then viral entry is blocked, but specificity of targeting is required to avoid off-target effects

Engineering Contradiction:

Improveinhibition of viral entryVSAvoidoff-target effects of modulators

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by targeting specific residues and binding interfaces of host cell proteins (B2M, NRP2, THBD) that are uniquely involved in HCMV entry. The modulators are designed to bind with high specificity to these localized regions, ensuring that viral entry is inhibited without affecting other cellular processes, thereby avoiding off-target effects.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent replaces broad-spectrum antiviral mechanisms with highly specific molecular interactions. Instead of using non-specific antiviral agents, the invention employs modulators that engage in precise lock-and-key interactions with specific protein interfaces, substituting mechanical specificity at the molecular level to achieve reliable viral entry inhibition without off-target effects.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Data Source

PatentEP4348257B1Methods for modulating host cell surface interactions with human cytomegalovirus

Publication Date: 2026.02.04 GENENTECH INC

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AI summary

Provided herein are methods of treating or preventing human cytomegalovirus (HCMV) infection comprising modulating interactions between the HCMV gH/gL/UL128-131 A pentamer and plasma membrane-expressed host cell proteins, as well as methods of identifying modulators of such interactions.