Combination Therapy for EV71 Infection Using Synergistic Drug Mixture
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Solution Overview
Problem
Current antiviral agents are ineffective against EV71 infections, and the development of specific antiviral strategies is hindered by the frequent generation of viral variants with antiviral resistance due to the lack of proofreading activity in the RNA-dependent RNA polymerase of EV71, necessitating a revised approach for effective treatment.
Innovation Solution
A combination therapy using auranofin, ouabain, emetine, niclosamide, and S-(+)-fluoxetine at non-effective levels, which exhibit synergistic activity against EV71 replication, providing a potent treatment for EV71 infections and hand, foot, and mouth disease.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a single antiviral agent is used to treat EV71 infection, then the treatment approach is simple, but the agent is ineffective against EV71 replication
Solution Approach 1:
The patent combines multiple compounds (auranofin, ouabain, emetine, niclosamide, and S-(+)-fluoxetine) into a single therapeutic regimen. Each compound individually shows limited anti-EV71 activity, but their combination produces synergistic effects that strongly suppress EV71 replication, thereby resolving the contradiction between treatment simplicity and effectiveness.
Solution Approach 2:
The invention creates a composite therapeutic approach by formulating a mixture of five different compounds. This composite therapy leverages the complementary mechanisms of action of each compound to achieve potent anti-EV71 activity that none of the individual compounds can achieve alone, thus improving reliability without requiring an overly complex treatment protocol.
2Reliability
If high concentrations of a single compound are used to achieve antiviral effect, then the antiviral activity is sufficient, but the toxicity to host cells increases
Solution Approach 1:
The patent employs each compound at sub-therapeutic or partial doses that individually would not achieve sufficient antiviral activity or would be toxic. However, in combination, these partial actions synergize to produce a potent antiviral effect at lower, safer concentrations for each individual compound, thereby resolving the contradiction between antiviral activity and host cell toxicity.
Solution Approach 2:
By merging multiple compounds at low doses, the therapy achieves the antiviral effect of high-dose monotherapy without the associated toxicity. The synergistic interaction among the compounds allows each to contribute partially to the overall antiviral activity while maintaining safe individual concentrations, thus reducing harmful effects on host cells.
3Device complexity
If monotherapy is used to simplify treatment, then the treatment protocol is simple, but viral variants with antiviral resistance can emerge
Solution Approach 1:
The patent combines multiple compounds with different mechanisms of action into a single treatment protocol. This combination approach maintains relative simplicity while effectively preventing viral resistance, as EV71 would need to simultaneously develop resistance to multiple different mechanisms of action, which is statistically improbable. This resolves the contradiction between protocol simplicity and resistance susceptibility.
Solution Approach 2:
The composite therapeutic regimen uses five compounds that target different aspects of viral replication. This multi-target approach creates a robust treatment protocol that remains simple to administer while being highly effective at preventing resistance development, as the viral genome would need to acquire multiple simultaneous mutations to evade all five compounds.
Data Source
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AI summary
The present invention is related to a combination for treating an EV71 infection, which comprises two or more compounds at each's non-effective level and provides an unexpected synergistic activity against EV71 replication, wherein the compound is selected from the group consisting of auranofin, ouabain, emetine, niclosamide, and S- (+) -fluoxetine.