Acyclic Fleximer Nucleoside Analogues for Coronavirus Inhibition
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Solution Overview
Problem
Current treatments and vaccines are lacking for human coronaviruses, particularly severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), with existing antiviral drugs showing little to no activity against these viruses, highlighting the need for new and effective antiviral therapeutics.
Innovation Solution
Development of acyclic fleximer nucleoside analogues that can bind to both natural and mutated polymerases of coronaviruses, offering increased flexibility and potential binding sites, thereby inhibiting viral replication.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing antiviral drugs (acyclovir, ganciclovir, lamivudine, zidovudine) are used to treat coronavirus infections, then the treatment approach follows established protocols, but the drugs exhibit little to no activity against SARS-CoV and MERS-CoV
Solution Approach 1:
The patent modifies the chemical structure of existing nucleoside analogues by changing parameters such as the sugar moiety (replacing ribose with acyclic analogues), base modifications, and stereochemical configurations to create new compounds with improved antiviral activity against coronaviruses while maintaining selectivity
Solution Approach 2:
The invention combines elements from different nucleoside structures (e.g., acyclovir's acyclic sugar, ribavirin's broad-spectrum activity profile, and other nucleoside features) to create hybrid compounds that exhibit enhanced antiviral properties against multiple coronavirus strains
2Adaptability or versatility
If ribavirin is used to inhibit coronavirus replication, then broad-spectrum antiviral activity is achieved, but the inhibitory concentration required is much higher (500-5000 μg/ml) than that needed to inhibit other viruses
Solution Approach 1:
The patent optimizes the chemical parameters of nucleoside analogues including the acyclic sugar configuration, base attachments, and molecular flexibility to achieve high antiviral potency at lower concentrations while maintaining broad-spectrum activity against different coronavirus strains
Solution Approach 2:
The invention introduces flexible acyclic sugar moieties that can dynamically adapt their conformation to fit different viral polymerase active sites, enhancing binding affinity and potency across multiple coronavirus types without requiring high concentrations
3Reliability
If nucleoside analogues are designed to inhibit viral replication, then antiviral activity is achieved, but there is a risk of injuring the host cell
Solution Approach 1:
The patent designs nucleoside analogues with specific local modifications (e.g., particular base attachments, stereochemical configurations, and acyclic sugar structures) that enable selective recognition and binding to viral polymerases while minimizing interaction with host cell enzymes, thereby achieving antiviral activity with reduced host cell toxicity
Data Source
AI summary
The present invention is directed to compounds, methods and compositions for treating or preventing viral infections using nucleosides analogs. Specifically, the present invention provides for the design and synthesis of acyclic fleximer nucleoside analogues having increased flexibility and ability to alter their conformation structures to provide increased antiviral activity potential with the result of inhibiting several coronaviruses.