Cyclic NTCP-Targeting Peptides for HBV Entry Inhibition
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Solution Overview
Problem
Current treatments for chronic hepatitis B virus (HBV) infections are limited in effectiveness, with only 10-25% of patients achieving a sustained virological response, and there is a need for novel therapeutics that target the virus's entry steps to potentially cure the infection, as existing therapies mainly focus on post-infection replication or immune modulation.
Innovation Solution
Development of cyclic NTCP targeting peptides derived from the hepatitis B virus (HBV) preS-domain, which are designed to inhibit the virus's entry into hepatocytes by targeting the sodium taurocholate co-transporting polypeptide (NTCP) receptor, potentially offering a new approach for the diagnosis, prevention, and treatment of HBV and related liver diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current therapeutic regimens (reverse transcriptase inhibitors, interferon alpha) are used to treat chronic HBV infections, then replication steps are addressed or immune system is modulated, but sustained virological response is achieved in only 10-25% of patients
Solution Approach 1:
The patent applies preliminary action by targeting virus entry (a pre-replication step) before the virus establishes infection and begins replication. The cyclic peptides block HBV and HDV entry into hepatocytes by targeting NTCP, preventing infection before replication occurs, which addresses the limitation of current therapies that only act after infection is established.
2Adaptability or versatility
If reverse transcriptase inhibitors are used to address viral replication, then post-infection replication steps are targeted, but virus entry step remains unaffected
Solution Approach 1:
The patent applies segmentation by dividing the antiviral therapeutic approach into distinct stages: entry inhibition (addressed by cyclic peptides targeting NTCP) and replication inhibition (addressed by reverse transcriptase inhibitors). This segmentation allows each therapy to target its specific stage optimally, with the cyclic peptides filling the gap in entry step coverage that RT inhibitors cannot address.
3Reliability
If entry inhibition therapy is implemented using cyclic NTCP-targeting peptides, then virus entry is blocked with curative potential, but novel therapeutic approach requires development and validation
Solution Approach 1:
The patent uses NTCP (sodium taurocholate co-transporting polypeptide) as an intermediary target. The cyclic peptides do not directly eliminate the virus but instead bind to NTCP on hepatocyte surfaces, acting as intermediaries that block viral entry. This intermediary approach provides curative potential while using a well-defined biological target that can be studied and optimized.
Data Source
AI summary
The present invention relates to cyclic NTCP targeting peptides which are preS-derived peptides of hepatitis B virus (HBV). The present invention further relates to pharmaceutical compositions comprising at least one cyclic peptide. The present invention further relates to medical uses of said cyclic peptides and the pharmaceutical compositions, such as in the diagnosis, prevention and/or treatment of a liver disease or condition, and/or in the inhibition of HBV and/or HDV infection. The present invention further relates to methods of diagnosis, prevention and/or treatment of a liver disease or condition and/or the inhibition of HBV and/or HDV infection.