Complement Modulators for Viral Lung Injury
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Solution Overview
Problem
Current strategies are inadequate for effectively preventing and treating lung injury caused by viral infections, such as those from coronavirus and influenza, due to excessive complement activation leading to inflammatory responses and tissue damage.
Innovation Solution
Administering modulators of the complement pathway, specifically inhibitors of the classical, alternate, and lectin pathways, including C5/C5a axis inhibitors like eculizumab and olendalizumab, to reduce terminal complement component levels and alleviate lung injury.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If the complement system is activated to defend against viral pathogens, then immune defense function is improved, but excessive complement activation causes lung injury and inflammatory damage
Solution Approach 1:
The patent uses C5a receptor antagonists as intermediary substances that block the harmful signaling between C5a and its receptor, preventing the transmission of inflammatory signals while allowing the complement system to continue its defensive functions. This mediator approach selectively interrupts the pathological pathway without completely disabling the complement system.
Solution Approach 2:
The patent modifies the regulatory parameters of the complement system by introducing C5aR antagonists that change the receptor's state from active to inactive, thereby altering the system's response threshold and preventing excessive activation while maintaining baseline protective functions.
2Reliability
If C3 deposition occurs during viral infection, then complement-mediated immune response is enhanced, but C3 deposition contributes to pulmonary disease and inflammatory cell recruitment
Solution Approach 1:
The patent extracts and targets the specific harmful component C5a from the complement cascade, using C5aR antagonists to selectively block this particular pathway while allowing other complement functions to proceed normally. This extraction approach isolates the harmful element without disrupting the overall immune response.
3Power
If C5a-C5aR signaling is activated, then inflammatory response is amplified, but this leads to increased tissue damage and lung dysfunction
Solution Approach 1:
The patent applies preliminary anti-action by pre-administering C5aR antagonists before or during early stages of viral infection, preventing the harmful C5a-C5aR signaling from being activated in the first place. This preemptive blocking stops the inflammatory amplification loop before it can cause significant tissue damage.
Data Source
AI summary
The present disclosure relates to, inter alia, a method of treating a complement mediated disorder caused by a virus, e.g., corona virus; Dengue virus (DENY); Ross River vims (RRV) and/or influenza virus (flu) by administering an effective amount of a complement modulator, such as, e.g., C5 inhibitor, such as eculizumab or an eculizumab variant or a C5a inhibitor such as olendalizumab (ALXN1007) or a variant thereof, to the subject. In addition, the present disclosure relates to, inter alia, a method of treating human patients inflicted with severe coronavirus disease-2019 (severe COVID-19) who is undergoing treatment with eculizumab. The method includes measuring a level of circulating component C5b-9 (membrane attack complex), in the patient's blood sample to titrate an effective eculizumab dose for the treatment of COVID-19.