Nanobody Cyclodextrin Quercetin Antiviral Formulation

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Solution Overview

Problem

Current methods are inadequate for effectively preventing or treating infections caused by enveloped viruses, such as SARS-CoV-2, as they fail to stabilize or reduce the virus presence in human or animal hosts.

Innovation Solution

A formulation combining engineered nanobodies targeting viral antigens or host cell receptors with Hydroxypropyl-Beta-Cyclodextrin (HPβCD) and the flavonoid quercetin, administered via nasal or pulmonary routes, to extract cholesterol from virus membranes and inhibit viral replication by facilitating zinc entry into host cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional methods are used to prevent or treat enveloped virus infections, then the treatment approach is simple, but the methods fail to stabilize or reduce virus presence in hosts

Engineering Contradiction:
Improveeffectiveness in preventing/treating virus infectionVSAvoidcomplexity of formulation
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent combines three distinct components (nanobody, cyclodextrin, and quercetin) into a single formulation to achieve synergistic effects. The nanobody targets viral antigens, cyclodextrin extracts cholesterol from virus membranes, and quercetin facilitates zinc entry into host cells - together they provide comprehensive protection that none could achieve alone.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The formulation uses a composite approach by integrating multiple biologically active substances with different mechanisms of action. This composite formulation addresses the limitations of single-component treatments by combining proteins (nanobody), carbohydrates (cyclodextrin), and flavonoids (quercetin) to create a multi-functional antiviral agent.

Inventive Principle:
Principle #40Composite materials

2Reliability

If nanobodies alone are used to block viral entry, then the mechanism is straightforward, but they may not sufficiently alter virus membrane structure

Engineering Contradiction:
Improveviral entry blockadeVSAvoidmechanism complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent divides the antiviral protection into three separate functional components: (1) nanobody for blocking viral entry by binding to viral antigens or host receptors, (2) cyclodextrin for extracting cholesterol from virus membranes to alter membrane structure, and (3) quercetin for facilitating zinc entry into host cells to inhibit replication. Each segment addresses a specific aspect of viral infection.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The formulation uses intermediaries to achieve its effects: nanobodies act as intermediaries to block the interaction between virus and host cell, cyclodextrin acts as an intermediary to extract and remove cholesterol from virus membranes, and quercetin acts as an intermediary to facilitate zinc transport into host cells. These intermediaries enable the formulation to modify virus structure and inhibit replication effectively.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If cyclodextrin is used to extract cholesterol from virus membranes, then viral entry is reduced, but additional mechanisms are needed to inhibit replication

Engineering Contradiction:
Improveviral entry preventionVSAvoidformulation composition
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The formulation performs preliminary actions at multiple stages of viral infection: cyclodextrin pre-treats the virus by extracting cholesterol from the membrane before entry, nanobody pre-blocks the entry pathway by binding to viral antigens or host receptors, and quercetin pre-prepares host cells by facilitating zinc entry to create an intracellular environment hostile to viral replication. These preliminary actions prevent infection before it can establish itself.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The formulation ensures continuous protection throughout the viral infection process by maintaining active components that work continuously: nanobodies continuously block viral entry, cyclodextrin continuously extracts cholesterol from virus membranes, and quercetin continuously facilitates zinc entry into host cells. This continuous action ensures that all stages of viral infection are addressed without interruption.

Inventive Principle:
Principle #20Continuity of useful action

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

This combination prevents viral entry into host cells by altering lipid and protein profiles and inhibits viral replication, providing both prophylactic and therapeutic protection against enveloped viruses, including SARS-CoV-2 and its variants.

Implementation Method 1

Hydroxypropyl-Beta-Cyclodextrin (HPβCD)...extract cholesterol molecules to various extents from enveloped virus membranes

Methodology Applied
Scientific EffectExtraction:

Implementation Method 2

extract cholesterol molecules to various extents from enveloped virus membranes, including that of SARS-CoV-2 and its variants

Methodology Applied
Scientific EffectLipid extraction: Liquid-Liquid Extraction

Implementation Method 3

the flavonoid quercetin...facilitating zinc entry into host cells

Methodology Applied
Scientific EffectIon transport:

Implementation Method 4

the flavonoid quercetin, a naturally occurring plant-based over the counter zinc ionophore

Methodology Applied
Scientific EffectMetal ion transport: Ion Exchange

Data Source

PatentUS20230357329A1Combined use of nanobody, cyclodextrin and quercetin for protection from enveloped viruses
Publication Date: 2023.11.09 VIRON INC

AI summary

Disclosed are engineered nanobodies against different target antigens such as the spike protein of the SARS-CoV-2 virus and or to the ACE2 receptor at the host cell surface, binds to the virus or the ACE2 receptor at the host cell plasma membrane, preventing entry of the SARS-CoV-2 virus.