Cordycepin Blocks Poly A Tail Polymerization

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Solution Overview

Problem

COVID-19 caused by Coronaviruses leads to systemic effects due to excessive ATP usage during polyadenylation, compromising cyclic AMP levels and disrupting normal cellular activity, resulting in severe symptoms.

Innovation Solution

Administration of 3′-deoxyadenosine, either alone or in combination with an inhibitor of adenosine receptors A1 and A3, or an agonist of receptors A2a and A2b, such as inosine, to block poly A tail polymerization and restore cyclic AMP levels, thereby inhibiting viral replication.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If poly A tail polymerization is performed using ATP during viral replication, then viral protein synthesis efficiency is improved, but intracellular cyclic AMP levels are depleted and normal cellular activity is disrupted

Engineering Contradiction:

Improveviral protein synthesis efficiencyVSAvoidintracellular cyclic AMP concentration

Core Design Contradiction:

ProductivityVSQuantity of substance

Solution Approach 1:

The patent extracts the harmful poly A tail polymerization process from the viral replication system by administering cordycepin, which selectively inhibits this specific enzymatic reaction without affecting other cellular processes. This removes the source of ATP depletion and cyclic AMP disruption while allowing viral replication to proceed at reduced efficiency

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the chemical parameter of the nucleoside structure by using cordycepin (3'-deoxyadenosine) instead of normal adenosine. This structural modification allows the molecule to be incorporated into the poly A tail synthesis pathway and act as a chain terminator, thereby altering the polymerization process to prevent excessive ATP consumption and cyclic AMP depletion

Inventive Principle:

Principle #35Parameter changes

2Reliability

If adenosine is administered to restore cyclic AMP levels, then cellular function is improved, but side effects are induced

Engineering Contradiction:

Improvecellular functionVSAvoidside effects

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent converts the harmful excessive poly A tail polymerization into a beneficial therapeutic effect by using cordycepin to selectively inhibit this process. The same enzymatic pathway that causes harm (poly A polymerase) becomes the target for therapeutic intervention, transforming the viral replication advantage into a vulnerability that can be exploited for treatment

Inventive Principle:

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

3Productivity

If poly A tail length is increased to enhance viral translation efficiency, then viral replication is improved, but ATP consumption increases and compromises physiological concentration

Engineering Contradiction:

Improveviral translation efficiencyVSAvoidATP consumption

Core Design Contradiction:

ProductivityVSUse of energy by moving object

Solution Approach 1:

The patent uses cordycepin to cause rapid chain termination in the poly A tail synthesis process. Instead of allowing the polymerization to proceed to completion and consume large amounts of ATP, the modified nucleoside causes the enzymatic reaction to stop prematurely, thereby 'skipping' the energy-intensive portion of the process while still producing some functional viral proteins

Inventive Principle:

Principle #21Skipping (Rushing through)

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

This approach effectively prevents viral replication and reduces the severity of COVID-19 symptoms by maintaining normal cyclic AMP levels and restoring cellular function without inducing side effects associated with adenosine administration.

Implementation Method 1

3'-deoxyadenosine or Cordycepin... to block poly A tail polymerization... prevents viral replication

Methodology Applied

Scientific EffectChain termination:

Implementation Method 2

the poly A polymerase enzyme, or PAP, uses ATP as donor molecules of the single ADENOSINE nucleotides required for the polymerization of the poly A tail

Methodology Applied

Scientific EffectPolymerization:

Implementation Method 3

This enzyme converts ATP into cyclic AMP or cAMP

Methodology Applied

Scientific EffectEnzymatic conversion: Enzyme

Data Source

PatentUS20230330126A1Modified adenosine nucleoside for use in the treatment of viral infections

Publication Date: 2023.10.19 IACHETTINI GIAMPIETRO

AI summary

An antiviral treatment of infections from Coronavirus, in particular COVID-19, is by administration of a modified nucleoside, derived from adenosine, individually or in combination with other therapeutically active substances. In particular, 3′-deoxyadenosine, or cordycepin, is administered for the treatment of a viral syndrome from Coronavirus, in particular COVID-19, in which 3′-deoxyadenosine is administered individually or in combination with at least one inhibitor or antagonist of the adenosine receptors A1 and A3 and possibly agonist of the adenosine receptors A2a and/or A2b. The administration of 3′-deoxyadenosine is subsequent or simultaneous to the administration of the inhibitor, preferably inosine, a molecule which expresses both these functions.