Lipidomics and metabolomics signatures of SARS-CoV-2 mediators/receptors in peripheral leukocytes, jejunum and colon

Geltrude Mingrone, Marco Federici, Jordi Mayneris-Perxachs, José Maria Moreno-Navarrete, Marta Ballanti, Giovanni Monteleone, Omero Alessandro Paoluzi, Philippe Lefebvre, Bart Staels, Massimo Federici, Josep Puig, Josep Garre, Rafael Ramos, José-Manuel Fernández-Real

Risultato della ricerca: Contributo in rivistaArticolo in rivista

Abstract

Cell surface receptor-mediated viral entry plays a critical role in this infection. Well-established SARS-CoV-2 receptors such as ACE2 and TMPRSS2 are highly expressed in the gastrointestinal tract. In fact, there are evidences that SARS-CoV-2 infects epithelial cells from the digestive system. However, emerging research has identified novel mediators such as DPP9, TYK2, and CCR2, all playing a critical role in inflammation. We evaluated the expression of SARS-CoV-2 receptors in peripheral leukocytes (n = 469), jejunum (n = 30), and colon (n = 37) of three independent cohorts by real-time PCR, RNA-sequencing, and microarray transcriptomics. We also performed HPCL-MS/MS lipidomics and metabolomics analyses to identify signatures linked to SARS-CoV-2 receptors. We found markedly higher peripheral leukocytes ACE2 expression levels in women compared to men, whereas the intestinal expression of TMPRSS2 was positively associated with BMI. Consistent lipidomics signatures associated with the expression of these mediators were found in both tissues and peripheral leukocytes involving n-3 long-chain PUFAs and arachidonic acid-derived eicosanoids, which play a key role in the regulation of inflammation and may interfere with viral entry and replication. Medium- and long-chain hydroxy acids, which have shown to interfere in viral replication, were also liked to SARS-CoV2 receptors. Gonadal steroids were also associated with the expression of some of these receptors, even after controlling for sex. The expression of SARS-CoV2 receptors was associated with several metabolic and nutritional traits in different cell types. This information may be useful in the design of potential therapies targeted at coronavirus entry.
Lingua originaleEnglish
pagine (da-a)6080-6089
Numero di pagine10
RivistaComputational and Structural Biotechnology Journal
Volume19
DOI
Stato di pubblicazionePubblicato - 2021

Keywords

  • Lipidomics
  • Metabolomics
  • Viral receptors
  • SARS-CoV-2
  • Omega-3 fatty acids

Fingerprint

Entra nei temi di ricerca di 'Lipidomics and metabolomics signatures of SARS-CoV-2 mediators/receptors in peripheral leukocytes, jejunum and colon'. Insieme formano una fingerprint unica.

Cita questo