The metabolic footprint of Vero E6 cells highlights the key metabolic routes associated with SARS-CoV-2 infection and response to drug combinations

{ 'indexed': {'date-parts': [[2024, 4, 5]], 'date-time': '2024-04-05T00:52:56Z', 'timestamp': 1712278376048}, 'reference-count': 75, 'publisher': 'Springer Science and Business Media LLC', 'issue': '1', 'license': [ { 'start': { 'date-parts': [[2024, 4, 4]], 'date-time': '2024-04-04T00:00:00Z', 'timestamp': 1712188800000}, 'content-version': 'tdm', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0'}, { 'start': { 'date-parts': [[2024, 4, 4]], 'date-time': '2024-04-04T00:00:00Z', 'timestamp': 1712188800000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0'}], 'funder': [ { 'DOI': '10.13039/501100009873', 'name': 'Regione Autonoma della Sardegna', 'doi-asserted-by': 'publisher', 'award': ['art. 9 L.R. 20/2015']}], 'content-domain': {'domain': ['link.springer.com'], 'crossmark-restriction': False}, 'abstract': '<jats:title>Abstract</jats:title><jats:p>SARS-CoV-2 burdens healthcare systems worldwide, yet ' 'specific drug-based treatments are still unavailable. Understanding the effects of SARS-CoV-2 ' 'on host molecular pathways is critical for providing full descriptions and optimizing ' 'therapeutic targets. The present study used Nuclear Magnetic Resonance-based metabolic ' 'footprinting to characterize the secreted cellular metabolite levels (exometabolomes) of Vero ' 'E6 cells in response to SARS-CoV-2 infection and to two candidate drugs (Remdesivir, RDV, and ' 'Azithromycin, AZI), either alone or in combination. SARS-CoV-2 infection appears to force VE6 ' 'cells to have increased glucose concentrations from extra-cellular medium and altered ' 'energetic metabolism. RDV and AZI, either alone or in combination, can modify the ' 'glycolic-gluconeogenesis pathway in the host cell, thus impairing the mitochondrial oxidative ' 'damage caused by the SARS-CoV-2 in the primary phase. RDV treatment appears to be associated ' 'with a metabolic shift toward the TCA cycle. Our findings reveal a metabolic reprogramming ' 'produced by studied pharmacological treatments that protects host cells against virus-induced ' 'metabolic damage, with an emphasis on the glycolytic-gluconeogenetic pathway. These findings ' 'may help researchers better understand the relevant biological mechanisms involved in viral ' 'infection, as well as the creation of mechanistic hypotheses for such candidate drugs, ' 'thereby opening up new possibilities for SARS-CoV-2 pharmacological therapy.</jats:p>', 'DOI': '10.1038/s41598-024-57726-3', 'type': 'journal-article', 'created': {'date-parts': [[2024, 4, 4]], 'date-time': '2024-04-04T15:02:53Z', 'timestamp': 1712242973000}, 'update-policy': 'http://dx.doi.org/10.1007/springer_crossmark_policy', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'The metabolic footprint of Vero E6 cells highlights the key metabolic routes associated with ' 'SARS-CoV-2 infection and response to drug combinations', 'prefix': '10.1038', 'volume': '14', 'author': [ {'given': 'Riccardo', 'family': 'Melis', 'sequence': 'first', 'affiliation': []}, {'given': 'Angela', 'family': 'Braca', 'sequence': 'additional', 'affiliation': []}, {'given': 'Daniela', 'family': 'Pagnozzi', 'sequence': 'additional', 'affiliation': []}, {'given': 'Roberto', 'family': 'Anedda', 'sequence': 'additional', 'affiliation': []}], 'member': '297', 'published-online': {'date-parts': [[2024, 4, 4]]}, 'reference': [ { 'key': '57726_CR1', 'doi-asserted-by': 'publisher', 'first-page': '727', 'DOI': '10.1056/NEJMoa2001017', 'volume': '382', 'author': 'N Zhu', 'year': '2020', 'unstructured': 'Zhu, N. et al. 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