Angiotensin II Type 2 Receptor Agonist for Respiratory Virus Damage

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current treatments for respiratory virus-induced tissue damage, such as those caused by coronaviruses like SARS-CoV and SARS-CoV-2, are inadequate in preventing severe respiratory diseases and promoting rapid recovery, particularly in patients with comorbidities like diabetes and hypertension, where ACE inhibitors and ARBs may increase the risk of severe infections.

Innovation Solution

The compound C21, a selective angiotensin II type 2 receptor agonist, is used to reduce E-cadherin expression in airway epithelial cells, thereby inhibiting viral binding and entry, and is administered to prevent and treat respiratory virus-induced tissue damage, including COVID-19, by reducing pulmonary inflammation and apoptosis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stress or pressure

If ACE inhibitors and ARBs are used to treat hypertension and diabetes, then blood pressure control is improved, but the risk of severe respiratory viral infections increases

Engineering Contradiction:
Improveblood pressure controlVSAvoidrisk of severe respiratory viral infections
Core Design Contradiction:
Stress or pressureVSObject-affected harmful factors

Solution Approach 1:

The patent introduces a new therapeutic agent (C21, a selective AT2R agonist) as an intermediary substance that mediates between the need for blood pressure control and the risk of viral infection. C21 activates the AT2 receptor to provide protective effects against viral infection while maintaining blood pressure control, thus resolving the contradiction by introducing a mediating substance with dual beneficial effects

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the therapeutic parameter from ACE inhibition or ARB mediation to direct AT2 receptor agonism. By shifting the mechanism of action to a different parameter (AT2R activation versus ACE inhibition), the treatment achieves both blood pressure control and enhanced protection against viral infection, resolving the contradiction through parameter transformation

Inventive Principle:
Principle #35Parameter changes

2Ease of operation

If current treatments are used for respiratory virus-induced tissue damage, then some symptom relief is achieved, but severe respiratory diseases still develop and recovery is prolonged

Engineering Contradiction:
Improvesymptom reliefVSAvoidprevention of severe respiratory diseases and recovery speed
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The patent applies preliminary action by administering C21 before severe respiratory disease develops or during early infection stages. The drug pre-activates protective mechanisms through AT2R agonism, including anti-inflammatory effects and prevention of epithelial cell damage, thereby preventing severe disease progression and accelerating recovery before full-blown pathology occurs

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent converts the harmful effects of viral infection into beneficial therapeutic opportunities. By using C21 to counteract the inflammatory response and tissue damage caused by the virus, the treatment transforms the pathological process into a controlled therapeutic response, where the same viral-induced inflammation that causes harm is countered by AT2R-mediated anti-inflammatory effects that promote recovery

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

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

C21 effectively abrogates the development of severe respiratory diseases, reduces the need for oxygen treatment, and decreases the number of patients requiring mechanical ventilation, promoting accelerated resolution of respiratory tissue damage and lung function restoration.

Implementation Method 1

The compound C21, a selective angiotensin II type 2 receptor agonist, is used to reduce E-cadherin expression in airway epithelial cells, thereby inhibiting viral binding and entry

Methodology Applied
Scientific EffectReceptor agonism:

Implementation Method 2

C21 effectively abrogates the development of severe respiratory diseases, reduces the need for oxygen treatment, and decreases the number of patients requiring mechanical ventilation, promoting accelerated resolution of respiratory tissue damage and lung function restoration

Methodology Applied
Scientific EffectAnti-inflammatory effect:

Data Source

PatentUS20220233480A1Use of angiotensin ii type 2 receptor agonist
Publication Date: 2022.07.28 VICORE PHARMA AB
  • US20220233480A1 patent drawing

AI summary

There is provided N-butyloxycarbonyl-3-(4-imidazol-1-ylmethylphenyl)-5-isobutylthiophene-2-sulfonamide, or a pharmaceutically-acceptable salt thereof, for use in a method of treatment of respiratory virus-induced tissue damage. Such damage may be caused by coronaviruses, including severe acute respiratory syndrome coronavirus and severe acute respiratory syndrome coronavirus. N-Butyloxycarbonyl-3-(4-imidazol-1-ylmethylphenyl)-5-iso-butylthiophene-2-sulfonamide alleviates symptoms of diseases caused by those viruses (including coronavirus disease 2019 or COVID-19), such as cough, dyspnea, pneumonia, respiratory distress, respiratory failure and/or fibrosis of organs such as the lungs, the heart or the kidneys, and may thus prevent respiratory virus-induced morbidity and/or mortality. In particular, it has been found in a clinical study that the proportion of patients with COVID-19 needing oxygen treatment was significantly lower for patients that were administered N-butyloxycarbonyl-3-(4-imidazol-1-ylmethylphenyl)-5-iso-butylthiophene-2-sulfonamide compared to placebo.