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Updated: Jul 23, 2025
11:12
Immunometabolic Circuits in Infection for Advancing Host Directed Therapies
Published on: September 13, 2024
449
SARS-CoV-2 infection dysregulates NAD metabolism
Amin Izadpanah1,2, Joseph C Mudd1,2, Joe G N Garcia3
1Tulane National Primate Research Center, Covington, Louisiana, LA, United States.
Frontiers in Immunology
|July 17, 2023
Summary
COVID-19 infection disrupts nicotinamide adenine dinucleotide (NAD) metabolism, increasing NAD turnover. Modulating NAD pathways with precursors like nicotinamide riboside (NR) may offer therapeutic benefits for COVID-19 and PASC.
Area of Science:
- Biochemistry
- Immunology
- Virology
Background:
- Severe COVID-19 causes pulmonary inflammation and persistent symptoms like fatigue and neurocognitive issues.
- Post-Acute Sequelae of COVID (PASC) symptoms may stem from dysregulated cellular metabolism.
- Nicotinamide adenine dinucleotide (NAD) is crucial for cellular energy and repair, and its metabolism can be altered during infection.
Purpose of the Study:
- To investigate the role of NAD metabolism in SARS-CoV-2 infection and PASC.
- To explore therapeutic strategies targeting NAD pathways for COVID-19 treatment.
Main Methods:
- RNA sequencing of mouse lungs infected with SARS-CoV-2 to analyze NAD pathway gene expression.
- Analysis of human patient lung sequencing data.
- Treatment of infected mice with nicotinamide riboside (NR) and an anti-NAMPT antibody.
Main Results:
- SARS-CoV-2 infection upregulated NAD biosynthetic and consuming enzymes, while downregulating SIRT1.
- NR treatment in mice mitigated lethality and improved recovery.
- Combined antibody and NR treatment altered lipid and nicotinamide metabolite profiles.
Conclusions:
- SARS-CoV-2 infection significantly perturbs NAD metabolism.
- Targeting NAD pathways presents a novel therapeutic strategy for COVID-19.
- Further research into NAD metabolism could reveal mechanisms underlying PASC and inform prevention strategies.
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