Formula I Nucleoside Analog Inhibits Viral Polymerase

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Solution Overview

Problem

Current treatments for Arenaviridae virus infections, such as Lassa and Junin viruses, lack effective therapies, and existing methods for Coronaviridae viruses like SARS and MERS do not provide sufficient therapeutic options, leading to high morbidity and mortality rates.

Innovation Solution

Administration of a therapeutically effective amount of a compound of Formula I or its pharmaceutically acceptable salt/ester, which inhibits Arenaviridae and Coronaviridae RNA-dependent RNA polymerase, thereby treating infections caused by these viruses.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If no approved therapy is administered for Lassa virus infection, then the virus replicates unchecked causing high mortality rates, but administering existing treatments like ribavirin does not provide sufficient therapeutic efficacy

Engineering Contradiction:
Improvetherapeutic efficacyVSAvoidmorbidity and mortality rates
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent modifies the chemical structure of ribavirin by replacing the ribose sugar moiety with various cyclic and acyclic carbon-based structures (Formula I compounds). This structural parameter change creates analogs with improved antiviral activity against Lassa virus and other Arenaviridae/Coronaviridae infections, overcoming the limitations of conventional ribavirin therapy

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention creates synthetic analogs (copies) of ribavirin with modified chemical structures that retain the core triazine ring system but incorporate improved pharmacological properties. These copied structures demonstrate enhanced therapeutic efficacy while maintaining the mechanism of action against viral RNA polymerase

Inventive Principle:
Principle #26Copying

2Reliability

If conventional treatments are used for Coronaviridae infections, then some symptomatic relief may be provided, but effective therapies are lacking leading to high morbidity and mortality

Engineering Contradiction:
Improvetherapeutic effectivenessVSAvoidmorbidity and mortality
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies structural modifications to create Formula I compounds that exhibit broad-spectrum activity against Coronaviridae viruses including SARS and MERS. The modified chemical parameters (cyclic vs acyclic carbon structures, various substituent groups) enhance viral replication inhibition compared to conventional treatments

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The Formula I compounds demonstrate multi-functionality by effectively treating infections from multiple virus families (Arenaviridae and Coronaviridae). This universal antiviral activity arises from the compounds' ability to inhibit RNA-dependent RNA polymerase across different viral systems, providing a broad-spectrum therapeutic solution

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 compound effectively treats Arenaviridae and Coronaviridae infections by inhibiting viral replication, reducing morbidity and mortality associated with these viruses.

Implementation Method 1

a compound of Formula I or a pharmaceutically acceptable salt or ester thereof which inhibits Arenaviridae and Coronaviridae RNA-dependent RNA polymerase

Methodology Applied
Scientific EffectEnzyme inhibition: Enzyme

Data Source

PatentEP4088718A1Methods for treating coronaviridae virus infections
Publication Date: 2022.11.16 GILEAD SCIENCES INC
  • EP4088718A1 patent drawingFigure 1
  • EP4088718A1 patent drawingFigure 2A~2B
  • EP4088718A1 patent drawingFigure 3A~3F

AI summary

Provided are methods for treating Coronaviridae virus infections by administering nucleosides and prodrugs thereof, of Formula I: wherein the 1' position of the nucleoside sugar is substituted.