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Influenza A Virus Studies in a Mouse Model of Infection
Published on: September 7, 2017
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Omicron Subvariants Infection Kinetics and Nirmatrelvir Efficacy in Transgenic K18-hACE2 Mice
Vijeta Sharma1, Enriko Dolgov1, Taylor Tillery1
1Center for Discovery and Innovation, Hackensack Meridian Health, 111 Ideation Way, Nutley, NJ 07110, USA.
International Journal of Molecular Sciences
|October 16, 2025
Summary
New SARS-CoV-2 Omicron subvariants like JN.1 show rapid infection kinetics and distinct immune responses. Direct-acting antiviral Nirmatrelvir remains effective, demonstrating significant viral load reduction in mice against these evolving variants.
Area of Science:
- Virology
- Immunology
- Pharmacology
Background:
- SARS-CoV-2 continuously evolves, leading to Omicron subvariants (e.g., JN.1, KP.3.1.1, LB.1) with enhanced transmissibility and immune evasion.
- Reduced efficacy of current vaccines and monoclonal antibodies necessitates exploring alternative therapeutics like direct-acting antivirals.
Purpose of the Study:
- To investigate the replication kinetics, immune responses, and therapeutic susceptibility of recent Omicron subvariants.
- To evaluate the efficacy of Nirmatrelvir against these emerging SARS-CoV-2 variants.
Main Methods:
- Utilized the K18-hACE2 transgenic mouse model to study three Omicron subvariants (JN.1, KP.3.1.1, LB.1) and the WA1/2020 parent strain.
- Monitored viral replication kinetics, pulmonary cytokine/chemokine profiles, and therapeutic response to Nirmatrelvir.
Main Results:
- Omicron subvariants demonstrated an early peak in lung viral titers (2 days post-infection) and accelerated pulmonary immune responses compared to WA1/2020.
- Nirmatrelvir treatment significantly reduced lung viral titers in subvariant-infected mice, showing greater efficacy than against the parent strain.
Conclusions:
- Infection with recent Omicron subvariants results in predictable viral burden dynamics and robust immune activation.
- Nirmatrelvir maintains significant therapeutic efficacy against emerging SARS-CoV-2 Omicron subvariants, highlighting its importance in combating viral evolution.
Keywords:
NirmatrelvirOmicron subvariantSARS-CoV-2animal modelantiviral agentspulmonary immune responseMore Related Videos
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