Filovirus Screening via Pseudotyped VSV Surrogates

Solution Overview

Problem

Current methods for researching and developing vaccines and antivirals against ebolaviruses are hindered by the challenges of working with biosafety level 4 agents, including limited BSL-4 space and personnel, and the lack of reproducibility of data from artificial systems with live viruses.

Innovation Solution

A method using a biologically contained Ebola virus (Ebolavirus ΔVP30) that lacks the VP30 gene, allowing for safe handling and high-throughput screening to identify modulators of filovirus infection, including the use of reporter gene assays and pseudotyped rhabdoviruses to test compounds for inhibitory effects.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If authentic Ebolaviruses are used for high throughput molecular screening, then the reliability of screening data is improved, but the feasibility of screening is worsened due to BSL-4 requirements

Engineering Contradiction:

Improvereliability of screening dataVSAvoidfeasibility of screening

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The patent creates a replication system that copies essential viral functions using recombinant vesicular stomatitis virus (VSV) particles pseudotyped with filovirus glycoproteins. This copy performs entry and fusion processes identical to authentic filoviruses but can be handled in lower BSL laboratories, resolving the contradiction between data reliability and screening feasibility

Inventive Principle:

Principle #26Copying

Solution Approach 2:

The patent uses pseudotyped VSV particles as an intermediary system. These particles mediate the study of filovirus entry and fusion mechanisms without requiring direct handling of BSL-4 authentic filoviruses. The VSV particle serves as a safe surrogate that reproduces key viral functions, enabling HTS in lower containment levels while maintaining biological relevance

Inventive Principle:

Principle #24Intermediary (Mediator)

2Ease of operation

If artificial systems are used to study viral life cycle, then the ease of operation is improved, but the reliability of data is worsened due to lack of reproducibility with live viruses

Engineering Contradiction:

Improveease of operationVSAvoidreliability of data

Core Design Contradiction:

Ease of operationVSReliability

Solution Approach 1:

The patent creates a replication system that copies essential viral functions using recombinant vesicular stomatitis virus (VSV) particles pseudotyped with filovirus glycoproteins. This copy performs entry and fusion processes identical to authentic filoviruses but can be handled in lower BSL laboratories, resolving the contradiction between data reliability and screening feasibility

Inventive Principle:

Principle #26Copying

Solution Approach 2:

The patent uses pseudotyped VSV particles as an intermediary system. These particles mediate the study of filovirus entry and fusion mechanisms without requiring direct handling of BSL-4 authentic filoviruses. The VSV particle serves as a safe surrogate that reproduces key viral functions, enabling HTS in lower containment levels while maintaining biological relevance

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS9222118B2Screen for inhibitors of filovirus and uses therefor

Publication Date: 2015.12.29 WISCONSIN ALUMNI RES FOUND

AI summary

The invention provides methods to identify agents useful to prevent, inhibit or treat viral infections, e.g. filovirus infections, as well as compositions having one or more agents to prevent, inhibit or treat viral infection.