Coronavirus Therapeutics Using Soluble S1/RBD Entry Blockers
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Solution Overview
Problem
Current therapies are inadequate for effectively preventing and treating infections caused by severe acute respiratory syndrome coronaviruses (SARS-COV-1 and SARS-COV-2) and their variants, particularly due to the challenges in blocking the interaction between the viral spike protein and the host cell receptor ACE2.
Innovation Solution
Administering soluble S1 and/or RBD proteins or ACE2 receptor proteins to compete with viral S1 proteins for binding to the ACE2 receptor, thereby inhibiting viral entry into host cells, which can be enhanced by linking these proteins to compounds that extend their serum half-life.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If soluble S1 and/or RBD proteins are administered to block viral entry, then viral infection is prevented, but the serum half-life of these proteins is limited
Solution Approach 1:
The patent creates fusion proteins by combining the S1/RBD domain with Fc portions of antibodies or other proteins (such as albumin). This composite structure leverages the long circulation half-life of the Fc portion or albumin while maintaining the viral binding capability of the S1/RBD domain, thereby extending the duration of action of the therapeutic agent without compromising its infection-blocking efficacy
2Reliability
If soluble ACE2 receptor proteins are administered to compete with viral binding, then viral entry is blocked, but the complexity of producing and stabilizing these proteins increases
Solution Approach 1:
The patent extracts and utilizes only the essential Fc portion of antibodies or other stable protein domains that provide long circulation half-life and structural stability. By combining this extracted functional element with the ACE2 or S1/RBD domain, the invention simplifies the overall protein structure while maintaining viral binding inhibition capability and reducing production complexity compared to using full-length complex proteins
3Reliability
If higher concentrations of soluble S1/RBD or ACE2 proteins are administered to ensure sufficient blocking, then viral infection is reduced, but the cost and potential side effects increase
Solution Approach 1:
The fusion protein design with Fc portions or albumin extensions increases the serum half-life of the therapeutic proteins, allowing them to remain at effective concentrations for longer periods. This reduces the frequency and total quantity of administrations needed to maintain sufficient blocking concentrations, thereby lowering the overall quantity of substance required while maintaining infection reduction efficacy
Data Source
AI summary
This invention provides compositions and methods to treat, prevent, and diagnose viral infections. The methods provided herein involve administering polypeptides of the invention to a subject in need thereof. The viral infections can be caused by a coronavirus such as SARS-COV-1, SARS-COV-2 or a variant thereof. It is contemplated that the polypeptide can be further linked to a compound, wherein the compound extends the serum half-life of the polypeptide.