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

Author(s)

Peinado, Rafaela dos S. ; Martins, Lucas G. ; Pacca, Carolina C. ; Saivish, Marielena V. ; Borsatto, Kelly C. ; Nogueira, Mauricio L. ; Tasic, Ljubica ; Arni, Raghuvir K. ; Eberle, Raphael J. ; Coronado, Monika A.

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 25, n. 3, p. 18-pg., 2024-02-01.

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-Barre 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. (AU)

• FAPESP's process: 23/09590-7 - Development of a diagnostic method for the rocio virus and the use of new compounds as inhibitors of the flavivirus NS2B-NS3 protease-helicase
• Grantee: Marielena Vogel Saivish
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 20/03639-6 - NMR metabolomics: metabolomic profiles of Vero cells infected with Zika and Chikungunya and inhibition by wedelolactone
• Grantee: Rafaela dos Santos Peinado
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 18/24069-3 - ReSEARCH: Recognizing Signatures of the Exposome to Anticipate the Risks for a Continuous Health
• Grantee: Fernando Barbosa Júnior
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/15083-2 - Synthesis and biological evaluation of isobavachalcone (IBC) and analogs as potential agents against tuberculosis
• Grantee: Luis Octávio Regasini
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/12875-5 - Development of the diagnostic method for Rocio virus and use of new compounds as inhibitors of flavivirus protease-helicase NS2B-NS3
• Grantee: Marielena Vogel Saivish
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/21719-3 - Epidemiological study of dengue (serotypes1-4) in a cohort of São José do Rio Preto, São Paulo, Brazil, during 2014-2018
• Grantee: Maurício Lacerda Nogueira
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 20/08615-8 - Protein exosites, cryptic sites and moonlighting: identification, functional mapping and effects of changes in structure
• Grantee: Raghuvir Krishnaswamy Arni
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/06510-4 - Application of Nuclear Magnetic Resonance (NMR) in metabolomics and metabonomics of human diseases
• Grantee: Ljubica Tasic
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/13341-1 - Search of compounds and peptides with potential antiviral activity against Arbovirus of clinical importance
• Grantee: Carolina Colombelli Pacca
• Support Opportunities: Regular Research Grants