Metabolic alterations upon SARS-CoV-2 infection and potential therapeutic targets against coronavirus infection

Abstract

The coronavirus disease 2019 (COVID-19) caused by coronavirus SARS-CoV-2 infection has become a global pandemic due to the high viral transmissibility and pathogenesis, bringing enormous burden to our society. Most patients infected by SARS-CoV-2 are asymptomatic or have mild symptoms. Although only a small proportion of patients progressed to severe COVID-19 with symptoms including acute respiratory distress syndrome (ARDS), disseminated coagulopathy, and cardiovascular disorders, severe COVID-19 is accompanied by high mortality rates with near 7 million deaths. Nowadays, effective therapeutic patterns for severe COVID-19 are still lacking. It has been extensively reported that host metabolism plays essential roles in various physiological processes during virus infection. Many viruses manipulate host metabolism to avoid immunity, facilitate their own replication, or to initiate pathological response. Targeting the interaction between SARS-CoV-2 and host metabolism holds promise for developing therapeutic strategies. In this review, we summarize and discuss recent studies dedicated to uncovering the role of host metabolism during the life cycle of SARS-CoV-2 in aspects of entry, replication, assembly, and pathogenesis with an emphasis on glucose metabolism and lipid metabolism. Microbiota and long COVID-19 are also discussed. Ultimately, we recapitulate metabolism-modulating drugs repurposed for COVID-19 including statins, ASM inhibitors, NSAIDs, Montelukast, omega-3 fatty acids, 2-DG, and metformin.

Effect of the SARS-CoV-2 pandemic on metabolic control in patients with type 2 diabetes: a 5-year cohort follow-up managed by a dynamic multidisciplinary team in Northeastern Mexico

“…The virus can also impair islet function by directly infecting pancreatic beta cells, restricting insulin secretion, and inducing cell apoptosis. Additionally, SARS-CoV-2 infection can shift glucose metabolism towards aerobic glycolysis through the Warburg effect [ 26 ].…”

“…Lipid accumulation has been observed in the lungs of SARS-CoV-2 patients. Furthermore, significant lipidomic alterations have been linked to SARS-CoV-2 severity since fatty acids are essential for SARS-CoV-2 replication [ 26 ].…”

Metabolic regulation of type I interferon production

“…Statins, which are targeting cholesterol metabolism significantly reduced risk of viral infection, including SARS-CoV-2 89,90 while data on mortality are unclear. 91 However, studies comparing the efficacy in humans are mostly retrospective, therefore comparing patients already using statins with cohorts without statin treatment. 89,[92][93][94] So, the effect of statins on an active viral infection are unclear.…”

“…Might the targeting of metabolic pathways be useful clinically to promote antiviral immunity or limit autoimmunity via modulation of type I IFNs? Statins, which are targeting cholesterol metabolism significantly reduced risk of viral infection, including SARS‐CoV‐2 89,90 while data on mortality are unclear 91 . However, studies comparing the efficacy in humans are mostly retrospective, therefore comparing patients already using statins with cohorts without statin treatment 89,92–94 .…”

Exploring Metabolic Anomalies in COVID-19 and Post-COVID-19: A Machine Learning Approach with Explainable Artificial Intelligence

“…One suitable factor accompanying the post-symptoms is metabolic reprogramming at the systemic level. Emerging evidence suggests these long-term consequences may be linked to systemic metabolic reprogramming during infection, affecting pathways related to amino acids, glucose, cholesterol, fatty acids, among others 12 . This metabolic disruption alters energy production and immune regulation, pointing to a need for further research to understand these changes and develop specific therapeutic interventions.…”