HCMV Pentamer Receptor Blocking for Viral Entry Prevention
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current vaccines and therapeutics against human cytomegalovirus (HCMV) show modest efficacy in preventing infection, and there is a need for effective treatments targeting the early steps of the HCMV infection cycle, particularly viral entry into host cells.
Innovation Solution
Identification and use of modulators that interfere with the interaction between the HCMV gH/gL/UL128-131A pentamer and host cell proteins such as beta-2-microglobulin (B2M), neuropilin 2 (NRP2), and thrombomodulin (THBD), using methods like surface plasmon resonance and biolayer interferometry to measure binding changes, and administering these modulators to individuals to treat or prevent HCMV infections.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current vaccines and therapeutics are used against HCMV, then some level of protection is provided, but the efficacy is only modest and insufficient for preventing infection
Solution Approach 1:
The patent identifies and targets specific host cell receptors (B2M, NRP2, THBD) that HCMV binds to during entry, and develops modulators that preemptively block these interactions before viral infection can occur. This preliminary blocking action prevents the virus from establishing infection in the first place, rather than treating after infection has occurred.
Solution Approach 2:
The patent uses modulators as intermediary molecules that bind to host cell receptors and prevent HCMV from binding to these receptors. These modulators act as mediators between the virus and host cell, blocking the harmful viral-receptor interaction without requiring direct contact with the virus itself.
2Reliability
If modulators are administered to block HCMV binding to host cell receptors, then infection is reduced by at least 40%, but the mechanism of action must be precisely targeted to specific receptor interactions
Solution Approach 1:
The patent develops modulators with highly specific local binding properties to particular host cell receptors (B2M, NRP2, or THBD) that HCMV uses for entry. Each modulator is designed to interact with specific local sites on these receptors, providing targeted blockade of viral binding without affecting other cellular functions.
Solution Approach 2:
The patent employs modulators that alter the binding parameters between HCMV and host cell receptors, specifically changing the affinity and specificity of these interactions. By modifying these binding parameters, the modulators effectively reduce viral attachment and entry efficiency.
3Reliability
If HCMV vaccines are developed to target early infection steps, then prevention efficacy should improve, but current vaccine candidates have failed to achieve high efficacy in clinical trials
Solution Approach 1:
Instead of trying to prevent HCMV infection through traditional vaccine approaches that target viral antigens, the patent inverts the strategy by targeting host cell receptors that the virus must bind to for entry. By blocking these essential host receptors with modulators, the invention achieves prevention without requiring the host to mount an immune response against the virus.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The modulators significantly decrease HCMV binding to host cell receptors, reducing infection by at least 40% and providing effective treatment and prevention of HCMV infections, especially in immunocompromised, pregnant, or infant individuals.
Implementation Method 1
using methods like surface plasmon resonance and biolayer interferometry to measure binding changes
Implementation Method 2
using methods like surface plasmon resonance and biolayer interferometry to measure binding changes
Data Source
Figure 1A~1C
Figure 1D~1H
Figure 2A~2D
AI summary
Provided herein are methods of treating or preventing human cytomegalovirus (HCMV) infection comprising modulating interactions between the HCMV gH/gL/UL128-131A pentamer and plasma membrane-expressed host cell proteins, as well as methods of identifying modulators of such interactions.