Human/SARS-CoV-2 genome-scale metabolic modeling to discover potential antiviral targets for COVID-19

Context-Specific Genome-Scale Metabolic Modelling and Its Application to the Analysis of COVID-19 Metabolic Signatures

“…The latter have employed different types of experimental data, such as data obtained from different cell lines (e.g., see [ 74 ]), patient samples (e.g., see [ 108 ]), or a combinations of both (e.g., [ 102 ]). Most of the approaches devoted to the GEM-based analysis of COVID-19 focused on the identification of enriched metabolic reactions and pathways (e.g., see [ 102 , 106 , 107 ]) and/or to the identification of potential antiviral targets (e.g., see [ 98 , 99 , 105 ]) and drug repurposing (e.g., see [ 100 , 103 ]). Reported studies also focused on the identification of metabolic reactions guiding disease severity [ 108 ], and on the analysis of cancer metabolism affected by SARS-CoV-2 infection [ 74 ].…”

“…Reported studies also focused on the identification of metabolic reactions guiding disease severity [ 108 ], and on the analysis of cancer metabolism affected by SARS-CoV-2 infection [ 74 ]. The approaches analysed different SARS-CoV-2 variants (e.g., see [ 99 , 105 ]) and infection dynamics in different cell types [ 109 ]. Finally, whole-body models were applied to analyse the consequences of the infection on the whole human body [ 110 ].…”

“…The VBOFs proposed by Renz et al [ 98 , 99 ] and Delattre et al [ 100 ] were later extended by Wang et al to increase their accuracy and to account for the Alpha and Delta variants of COVID-19 [ 105 ]. These VBOFs were integrated into Recon3D [ 21 ] to obtain variant-specific models.…”

Cell‐specific genome‐scale metabolic modeling of SARS‐CoV‐2‐infected lung to identify antiviral enzymes

“…Experimental findings have revealed substantial metabolic flux changes in infected host cells compared with their host counterparts [34][35][36]. These metabolic alterations can be used to compare the differential expression of metabolites between a hostvirus (HV) model and a host to identify potential therapeutic targets for the treatment of COVID-19 [37][38][39][40][41][42][43][44][45][46][47]. To investigate the metabolic fluxes of an HV cell, a viral biomass reaction (VBR) must be constructed using the viral genome sequence.…”

“…To investigate the metabolic fluxes of an HV cell, a viral biomass reaction (VBR) must be constructed using the viral genome sequence. In previous studies, the VBR of the alpha variant of SARS-CoV-2 was incorporated into the iAB-AMØ-1410 human alveolar macrophage model [40,[42][43][44] and the Recon2.2 and Recon3D human genome-scale metabolic models (GSMMs) [45][46][47][48][49] to examine the metabolic behavior of infected cells. However, based on a literature review, only a limited number of studies have endeavored to utilize a cell-specific GSMM for identifying antiviral enzymes aimed at treating infected HV cells.…”