Abstract
BackgroundOne of coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused coronavirus disease 2019 (COVID-19) pandemic and threatened worldwide. However, therapy for COVID-19 has rarely been proven to possess specific efficacy. As the virus relies on host metabolism for its survival, several studies have reported metabolic intervention by SARS-CoV-2.ResultsWe investigated the coronavirus-metabolic hijacking using mouse hepatitis virus (MHV) as a surrogate for SARS-CoV-2. Based on the altered host metabolism by MHV infection, an increase of glycolysis with low mitochondrial metabolism, we tried to investigate possible therapeutic molecules which increase the TCA cycle. Endogenous metabolites and metabolic regulators were introduced to restrain viral replication by metabolic intervention. We observed that cells deprived of cellular energy nutrition with low glycolysis strongly suppress viral replication. Furthermore, viral replication was also significantly suppressed by electron transport chain inhibitors which exhaust cellular energy. Apart from glycolysis and ETC, pyruvate supplement suppressed viral replication by the TCA cycle induction. As the non-glucose metabolite, fatty acids supplement decreased viral replication via the TCA cycle. Additionally, as a highly possible therapeutic metabolite, nicotinamide riboside (NR) supplement, which activates the TCA cycle by supplying NAD+, substantially suppressed viral replication.ConclusionsThis study suggests that metabolite-mediated TCA cycle activation suppresses replication of coronavirus and suggests that NR might play a role as a novel therapeutic metabolite for coronavirus.
Highlights
One of coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused corona‐ virus disease 2019 (COVID-19) pandemic and threatened worldwide
Alteration of host metabolism upon mouse hepatitis virus (MHV) infection Virus altered host metabolism, metabolic hijacking, has been investigated in diverse kinds of viruses, and glycolysis is shown to be increased by virus infection [26]
Though the virus relies on host metabolism for its survival and the host produces most of its energy in mitochondria, mitochondrial disruption by various kinds of viruses has been observed [27]
Summary
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused corona‐ virus disease 2019 (COVID-19) pandemic and threatened worldwide. In lineage B, the Sarbecovirus contains a Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 induced coronavirus disease 2019 (COVID-19) was defined as a pandemic by World Health Organization (WHO), and the number of death. Lee et al Cell & Bioscience (2022) 12:7 developing therapeutic agents had been in difficulty, diversely designed vaccines for SARS-CoV-2 have been introduced and obtained efficacy [7, 8]. As prevalence of SARS-CoV-2 mutants is expanding, there is still an urgent need to find an effective therapeutic approach for COVID-19 patients. SARS-CoV-2 has been known to induce and use the Warburg effect for their replication [13]. We tried to investigate metabolic regulators involved in viral suppression, which can be used as therapeutic agents
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