Antivirals Targeting the Neuraminidase
Larisa Gubareva1, Teena Mohan1
1Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30329-4027, USA.
Cold Spring Harbor Perspectives in Medicine
|March 11, 2020
Summary
Influenza neuraminidase (NA) inhibitors are crucial for treating infections. New strategies, including monoclonal antibodies and Fc-conjugates targeting NA, are being developed to overcome drug resistance and improve antiviral therapies.
Area of Science:
- Virology
- Immunology
- Drug Discovery
Background:
- Neuraminidase (NA) is essential for influenza A and B virus replication, with a conserved active site targeted by existing drugs.
- Current NA inhibitors (zanamivir, oseltamivir, peramivir, laninamivir) face challenges due to viral mutations causing drug resistance.
- The need for next-generation therapeutics targeting NA is driven by resistance and other limitations of current treatments.
Purpose of the Study:
- To explore novel therapeutic strategies targeting the conserved neuraminidase (NA) of influenza viruses.
- To evaluate the potential of monoclonal antibodies (mAbs) and antiviral Fc-conjugates as next-generation NA inhibitors.
- To highlight advancements in developing new antiviral agents against influenza.
Main Methods:
- Synthesis and testing of sialic acid analogs as NA inhibitors.
- Development and evaluation of anti-NA monoclonal antibodies (mAbs).
- Design and assessment of antiviral Fc-conjugates combining NA inhibitors with Fc-regions.
Main Results:
- Sialic acid analogs competitively bind to the NA active site, inhibiting enzyme activity.
- Anti-NA mAbs exhibit antiviral activity through Fab-binding and Fc-mediated immune functions.
- Antiviral Fc-conjugates offer a multimodal approach by combining NA inhibition with immune system engagement.
Conclusions:
- Neuraminidase remains a highly attractive target for developing novel influenza antiviral therapies.
- Monoclonal antibodies and Fc-conjugates represent promising next-generation strategies to combat influenza, potentially overcoming existing drug resistance.
- Continued research into NA-targeting therapeutics is vital for advancing influenza treatment options.
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