Small-molecule metabolome identifies potential therapeutic targets against COVID-19
| Autor: | Emily Moslinger, Martin Kaufmann, Prameet M. Sheth, Henry L. Wong, Anne K. Ellis, Calvin Sjaarda, Robert I. Colautti, Sean M.P. Bennet, Stephen Vanner, Kaede Takami, Katya Douchant, David E. Reed |
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| Rok vydání: | 2021 |
| Předmět: |
Metabolite
Carnosine Mucous membrane of nose Respiratory Syncytial Virus Infections Virus chemistry.chemical_compound Metabolomics Tandem Mass Spectrometry Influenza Human Metabolome Humans Medicine Receptor Multidisciplinary SARS-CoV-2 business.industry COVID-19 Lysophosphatidylcholines COVID-19 Drug Treatment chemistry Respiratory Syncytial Virus Human Immunology business Viral load Chromatography Liquid |
| DOI: | 10.1101/2021.06.18.21259150 |
| Popis: | BackgroundRespiratory viruses are transmitted and acquired via the nasal mucosa, and thereby may influence the nasal metabolome composed of biochemical products produced by both host cells and microbes. Studies of the nasal metabolome demonstrate virus-specific changes that sometimes correlate with viral load and disease severity. Here, we evaluate the nasopharyngeal metabolome of COVID-19 infected individuals and report several small molecules that may be used as potential therapeutic targets. Specimens were tested by qRT-PCR with target primers for three viruses: Influenza A (INFA), respiratory syncytial virus (RSV), and SARS-CoV-2, along with asymptomatic controls. The nasopharyngeal metabolome was characterized using an LC-MS/MS-based small-molecule screening kit capable of quantifying 141 analytes. A machine learning model identified 28 discriminating analytes and correctly categorized patients with a viral infection with an accuracy of 96% (R2=0.771, Q2=0.72). A second model identified 5 analytes to differentiate COVID19-infected patients from those with INFA or RSV with an accuracy of 85% (R2=0.442, Q2=0.301). Specifically, LysoPCaC18:2 concentration was significantly increased in COVID19 patients (P< 0.0001), whereas beta-hydroxybutyric acid, Met SO, succinic acid, and carnosine concentrations were significantly decreased (P< 0.0001). This study demonstrates that COVID19 infection results in a unique NP metabolomic signature with carnosine and LysoPCaC18:2 as potential therapeutic targets.Significance StatementEfforts to elucidate how SARS-CoV-2 interacts with the host has become a global priority. To identify biomarkers for potential therapeutic interventions, we used a targeted metabolomics approach evaluating metabolite profiles in the nasal mucosa of COVID-19 patients and compared metabolite profiles to those of other respiratory viruses (influenza A, RSV). We identified a COVID-19-specific signature characterized by changes to LysoPCaC18:2, beta-hydroxybutyric acid, Met SO, succinic acid, and carnosine. Carnosine is a promising potential target against SARS-CoV-2 as it has been shown to interfere with binding of SARS-CoV-2 to the ACE2 receptor. This study provides compelling evidence for the use of metabolomics as an avenue for the identification of novel drug targets for viral respiratory infections in the nasopharynx. |
| Databáze: | OpenAIRE |
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