Lectin Mutant Compounds for Viral Spike Inactivation

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Solution Overview

Problem

Current treatments for viral infections, such as HIV-1 and COVID-19 caused by SARS-CoV-2, lack effective methods for irreversible inactivation of viral spikes, leading to incomplete prevention of viral entry and transmission.

Innovation Solution

Development of lectin-based compounds, specifically mutant cyanovirin N (CVN) and Griffithsin (GRFT) linked with a flexible linker and a S2 binding domain, targeting the spike protein's metastable conformation to induce irreversible inactivation and virolysis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If traditional antiviral treatments are used, then viral infection can be partially inhibited, but irreversible inactivation of viral spikes is not achieved

Engineering Contradiction:
Improveinhibition of viral infectionVSAvoidirreversible inactivation of viral spikes
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The invention uses composite lectin structures (cyanovirin-N or griffithsin fused with binding domains) that combine glycan-binding capability with spike protein recognition, creating a material with dual functionality that achieves both infection inhibition and irreversible spike inactivation

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The lectin is divided into functional segments: a glycan-binding domain (cyanovirin-N or griffithsin) and a spike protein binding domain, connected by a linker peptide. This segmentation allows each domain to perform its specific function while working together to achieve irreversible viral spike inactivation

Inventive Principle:
Principle #1Segmentation

2Reliability

If lectin-based compounds targeting glycan sites are used, then viral entry is inhibited, but complete prevention of viral transmission is not achieved

Engineering Contradiction:
Improveprevention of viral entryVSAvoidprevention of viral transmission
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The lectin compound binds to and inactivates the viral spike protein before the virus can attach to and enter host cells. This preliminary inactivation of the spike protein prevents both viral entry and subsequent transmission, addressing the insufficiency of traditional entry inhibitors

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The lectin acts as an intermediary that bridges the glycan sites on the spike protein and forms stable complexes that prevent viral-cell interaction. The binding domain serves as an intermediary element that specifically recognizes spike protein structures, enhancing the prevention of viral transmission

Inventive Principle:
Principle #24Intermediary (Mediator)

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 lectin-based compounds effectively inhibit viral infection and promote virolysis by targeting the spike protein's glycan sites, demonstrating potent inhibition and lytic activity against various viral strains, including SARS-CoV-2 and HIV-1, with improved potency compared to traditional approaches.

Implementation Method 1

The lectin-based compounds effectively inhibit viral infection and promote virolysis by targeting the spike protein's glycan sites

Methodology Applied
Scientific EffectLectin-carbohydrate binding: Absorption (physical)

Data Source

PatentUS20230355708A1Compositions for inhibiting viral entry and methods using same
Publication Date: 2023.11.09 DREXEL UNIV
  • US20230355708A1 patent drawing
  • US20230355708A1 patent drawing
  • US20230355708A1 patent drawing

AI summary

The present disclosure relates, in part, to a composition for promoting virolysis and/or inhibition of infection of a vims in a mammal, the composition comprising a lectin mutant. In certain embodiments, the lectin mutant comprises mutant cyanovirin N (CVN) and mutant Griffithsin (GRFT). The present disclosure further provides methods of treating, preventing, and/or ameliorating viral infection in a subject. In certain embodiments, the viral infection is caused by a vims selected from the group consisting of SARS-CoV-1, SARS-CoV-2, and HIV-I. The present disclosure further provides cyclic compounds useful for the treatment, prevention, and/or amelioration of HIV-I in a subject.--