Dantrolene Calcium Modulation to Inhibit SARS-CoV-2 Replication
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Solution Overview
Problem
There is an urgent need for effective treatments against SARS-CoV-2 infections, particularly COVID-19, as the virus poses a significant threat to global public health and existing treatments are inadequate.
Innovation Solution
Dantrolene or its pharmaceutically acceptable salts and prodrugs, administered in therapeutically effective amounts, are used to inhibit SARS-CoV-2 replication, entry, maturation, and release from host cells by modulating intracellular calcium levels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing treatments are used for SARS-CoV-2 infections, then treatment availability is maintained, but treatment effectiveness is insufficient
Solution Approach 1:
The patent changes the chemical parameter by introducing dantrolene, a muscle relaxant with calcium channel blocking properties, to treat SARS-CoV-2. This parameter change (using a drug with different primary indication) achieves both treatment effectiveness against the virus and maintains treatment availability through repurposing an existing approved medication
2Productivity
If dantrolene is administered to inhibit viral replication, then viral replication is reduced, but the mechanism of action requires intracellular calcium modulation
Solution Approach 1:
The patent extracts and utilizes the calcium channel blocking property of dantrolene, separating this specific mechanism from its primary muscle relaxant indication. By focusing on the calcium modulation aspect, the drug effectively inhibits viral replication while simplifying the understanding of its mechanism to a specific molecular target
3Object-affected harmful factors
If Ca2+ ions promote coronavirus fusion with host cells, then viral entry is enhanced, but blocking calcium channels may inhibit viral entry
Solution Approach 1:
The patent converts the harmful effect of calcium ions (promoting viral fusion and entry) into a beneficial therapeutic mechanism. By blocking calcium channels with dantrolene, the same calcium dependency that aids viral entry becomes the target for inhibition, turning the virus's reliance on calcium into a vulnerability that can be exploited therapeutically
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
Dantrolene demonstrates a surprising effectiveness in reducing viral replication, improving clinical symptoms, and enhancing oxygen saturation and fever normalization in COVID-19 patients, with potential for broad-spectrum antiviral activity against SARS-CoV-2.
Implementation Method 1
Dantrolene or its pharmaceutically acceptable salts and prodrugs, administered in therapeutically effective amounts, are used to inhibit SARS-CoV-2 replication, entry, maturation, and release from host cells by modulating intracellular calcium levels
Data Source
AI summary
The disclosure is directed to methods of using dantrolene or a dantrolene prodrug, or a pharmaceutically acceptable salt thereof, to treat COVID-19 and SARS-CoV-2 infections.