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SARS‐CoV ‐2 infection impacts carbon metabolism and depends on glutamine for replication in Syrian hamster astrocytes

2022; Wiley; Volume: 163; Issue: 2 Linguagem: Inglês

10.1111/jnc.15679

1471-4159

Lilian Gomes de Oliveira, Yan de Souza Angelo, Pedro Takao Yamamoto, Victor Corasolla Carregari, Fernanda Crunfli, Guilherme Reis‐de‐Oliveira, Lícia Costa, Pedro Henrique Vendramini, Érica de Almeida Duque, Nilton Barreto dos Santos, Egidi Mayara Silva Firmino, Isadora Marques Paiva, Glaucia M. Almeida, Adriano Sebollela, Carolina Manganeli Polonio, Nágela Ghabdan Zanluqui, Marília Garcia de Oliveira, Patrick da Silva, Gustavo Gastão Davanzo, Marina Caçador Ayupe, Caio Loureiro Salgado, Antônio Francisco de Souza Filho, Marcelo Valdemir de Araújo, Taiana Tainá Silva‐Pereira, Angélica Cristine de Almeida Campos, Luiz Gustavo Bentim Góes, Marielton dos Passos Cunha, Élia Garcia Caldini, Maria Regina D’Império Lima, Denise Morais da Fonseca, Ana M. S. Guimarães, Paola Minoprio, Carolina Demarchi Munhoz, Cláudia Madalena Cabrera Mori, Pedro M. Moraes‐Vieira, Thiago M. Cunha, Daniel Martins‐de‐Souza, Jean Pierre Schatzmann Peron,

COVID-19 Clinical Research Studies

COVID-19 causes more than million deaths worldwide. Although much is understood about the immunopathogenesis of the lung disease, a lot remains to be known on the neurological impact of COVID-19. Here, we evaluated immunometabolic changes using astrocytes in vitro and dissected brain areas of SARS-CoV-2 infected Syrian hamsters. We show that SARS-CoV-2 alters proteins of carbon metabolism, glycolysis, and synaptic transmission, many of which are altered in neurological diseases. Real-time respirometry evidenced hyperactivation of glycolysis, further confirmed by metabolomics, with intense consumption of glucose, pyruvate, glutamine, and alpha ketoglutarate. Consistent with glutamine reduction, the blockade of glutaminolysis impaired viral replication and inflammatory response in vitro. SARS-CoV-2 was detected in vivo in hippocampus, cortex, and olfactory bulb of intranasally infected animals. Our data evidence an imbalance in important metabolic molecules and neurotransmitters in infected astrocytes. We suggest this may correlate with the neurological impairment observed during COVID-19, as memory loss, confusion, and cognitive impairment.