HR-MAS NMR Metabolomics Profile of Vero Cells under the Influence of Virus Infection and nsP2 Inhibitor: A Chikungunya Case Study

Author:

Peinado Rafaela dos S.1ORCID,Martins Lucas G.2ORCID,Pacca Carolina C.3,Saivish Marielena V.3ORCID,Borsatto Kelly C.1ORCID,Nogueira Maurício L.3ORCID,Tasic Ljubica2ORCID,Arni Raghuvir K.1ORCID,Eberle Raphael J.45ORCID,Coronado Mônika A.4ORCID

Affiliation:

1. Multiuser Center for Biomolecular Innovation, Department of Physics, Institute of Biosciences, Languages and Exact Sciences (Ibilce—UNESP), Sao Jose do Rio Preto, Sao Paulo 15054000, Brazil

2. Department of Organic Chemistry, Institute of Chemistry, University of Campinas (UNICAMP), Campinas 13083862, Brazil

3. Virology Research Laboratory, Medical School of Sao Jose do Rio Preto (FAMERP), Sao Paulo 15090000, Brazil

4. Institute of Biological Information Processing IBI-7: Structural Biochemistry, Forschungszentrum Jülich, 52428 Jülich, Germany

5. Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, 40225 Düsseldorf, Germany

Abstract

The arbovirus Chikungunya (CHIKV) is transmitted by Aedes mosquitoes in urban environments, and in humans, it triggers debilitating symptoms involving long-term complications, including arthritis and Guillain-Barré syndrome. The development of antiviral therapies is relevant, as no efficacious vaccine or drug has yet been approved for clinical application. As a detailed map of molecules underlying the viral infection can be obtained from the metabolome, we validated the metabolic signatures of Vero E6 cells prior to infection (CC), following CHIKV infection (CV) and also upon the inclusion of the nsP2 protease inhibitor wedelolactone (CWV), a coumestan which inhibits viral replication processes. The metabolome groups evidenced significant changes in the levels of lactate, myo-inositol, phosphocholine, glucose, betaine and a few specific amino acids. This study forms a preliminary basis for identifying metabolites through HR-MAS NMR (High Resolution Magic Angle Spinning Nuclear Magnetic Ressonance Spectroscopy) and proposing the affected metabolic pathways of cells following viral infection and upon incorporation of putative antiviral molecules.

Funder

FAPESP

CNPq

National Institutes of Health

INCT Viral Genomic Surveillance and One Health

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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