Can a metabolism-targeted therapeutic intervention successfully subjugate SARS-COV-2? A scientific rational - 28/10/20

Graphical abstract |
Highlights |
• | SARS-CoV-2 replication demands an upregulated cellular lipogenesis to support viral packaging. |
• | SARS-CoV-2-induced ARDS in the alveoli is the main culprit for COVID-19 fatality. |
• | Increased oxidative stress, as one of the key features of ARDS, could be overcome by high-dose vitamin C. |
• | A combination of metformin plus azythromycin/doxicycline could target viral replication by downregulating lipogenesis. |
• | We propose the combination of vitamin C plus metformin and azythromycin/doxicycline for the treatment of fatal SARS-CoV-2 attacks. |
Abstract |
As a process entailing a high turnover of the host cell molecules, viral replication is required for a successful viral infection and requests virus capacity to acquire the macromolecules required for its propagation. To this end, viruses have adopted several strategies to harness cellular metabolism in accordance with their specific demands. Most viruses upregulate specific cellular anabolic pathways and are largely dependent on such alterations. RNA viruses, for example, upregulate both glycolysisand glycogenolysis providing TCA cycle intermediates essential for anabolic lipogenesis. Also, these infections usually induce the PPP, leading to increased nucleotide levels supporting viral replication. SARS-CoV-2 (the cause of COVID-19)that has so far spread from China throughout the world is also an RNA virus. Owing to the more metabolic plasticity of uninfected cells, a promising approach for specific antiviral therapy, which has drawn a lot of attention in the recent years,
would be the targeting of metabolic changes induced by viruses. In the current review, we first summarize some of virus-induced metabolic adaptations and then based on these information as well as SARS-CoV-2 pathogenesis, propose a potential therapeutic modality for this calamitous world-spreading virus with the hope of employing this strategy for near-future clinical application.
Le texte complet de cet article est disponible en PDF.Keywords : SARS-CoV-2, Cellular metabolism, Glycolysis, PPP, TCA cycle
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Vol 131
Article 110694- novembre 2020 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.