Abstract
In this study we have developed a method based on Flux Balance Analysis to identify human metabolic enzymes which can be targeted for therapeutic intervention against COVID-19. A literature search was carried out in order to identify suitable inhibitors of these enzymes, which were confirmed by docking calculations. In total, 10 targets and 12 bioactive molecules have been predicted. Among the most promising molecules we identified Triacsin C, which inhibits ACSL3, and which has been shown to be very effective against different viruses, including positive-sense single-stranded RNA viruses. Similarly, we also identified the drug Celgosivir, which has been successfully tested in cells infected with different types of viruses such as Dengue, Zika, Hepatitis C and Influenza. Finally, other drugs targeting enzymes of lipid metabolism, carbohydrate metabolism or protein palmitoylation (such as Propylthiouracil, 2-Bromopalmitate, Lipofermata, Tunicamycin, Benzyl Isothiocyanate, Tipifarnib and Lonafarnib) are also proposed.
Highlights
In this study we have developed a method based on Flux Balance Analysis to identify human metabolic enzymes which can be targeted for therapeutic intervention against COVID-19
The scientific response to the COVID-19 pandemic has been unprecedented, with a huge number of studies developed in an attempt to rapidly unravel the pathogenesis of the disease and to propose potential therapeutic strategies, such as the recently approved COVID-19 vaccines or the promising treatments based on humanized monoclonal antibodies that can be used to treat the cytokine storm s yndrome[46]
The severity and mortality of the disease is associated with a high level of release of cytokine in the patients, which is known as cytokine storm syndrome
Summary
In this study we have developed a method based on Flux Balance Analysis to identify human metabolic enzymes which can be targeted for therapeutic intervention against COVID-19. The COVID-19 pandemic, caused by the virus SARS-CoV-2, has resulted in a substantial increase in mortality and serious economic and social disruption worldwide[1] In this context, the rapid identification of therapeutic molecules against SARS-CoV-2 is essential. The metabolic resources of the host cell are diverted to the formation of virions via the recruitment of metabolic enzymes and their localization in “replication and transcription complexes” (RTCs), which are vesicles formed from endoplasmic reticulum (ER) membranes, in which the virus replicates This recruitment takes place via the interaction of host enzymes with viral proteins, such as NSP3 of rotavirus, which recruits FASN, or NS5A of hepatitis C virus, which recruits phosphatidylinositol 4-kinase alpha (PI4KA)[4].
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