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. 2021 Aug 5;4(10):e202000954.
doi: 10.26508/lsa.202000954. Print 2021 Oct.

Integrated human/SARS-CoV-2 metabolic models present novel treatment strategies against COVID-19

Bridget P Bannerman  1   2 , Jorge Júlvez  3 , Alexandru Oarga  3 , Tom L Blundell  4 , Pablo Moreno  5 , R Andres Floto  6
Affiliations

Integrated human/SARS-CoV-2 metabolic models present novel treatment strategies against COVID-19

Bridget P Bannerman et al. Life Sci Alliance. .

Abstract

The coronavirus disease 2019 (COVID-19) pandemic caused by the new coronavirus (SARS-CoV-2) is currently responsible for more than 3 million deaths in 219 countries across the world and with more than 140 million cases. The absence of FDA-approved drugs against SARS-CoV-2 has highlighted an urgent need to design new drugs. We developed an integrated model of the human cell and SARS-CoV-2 to provide insight into the virus' pathogenic mechanism and support current therapeutic strategies. We show the biochemical reactions required for the growth and general maintenance of the human cell, first, in its healthy state. We then demonstrate how the entry of SARS-CoV-2 into the human cell causes biochemical and structural changes, leading to a change of cell functions or cell death. A new computational method that predicts 20 unique reactions as drug targets from our models and provides a platform for future studies on viral entry inhibition, immune regulation, and drug optimisation strategies. The model is available in BioModels (https://www.ebi.ac.uk/biomodels/MODEL2007210001) and the software tool, findCPcli, that implements the computational method is available at https://github.com/findCP/findCPcli.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1.
Figure 1.. The mechanism of replication of SARS-CoV-2 in the human cell.
Figure 2.
Figure 2.. SARS-CoV-2 viral genome and host-dependent metabolic pathways.
Figure 3.
Figure 3.. PPi-pathway intersection node—Nsp9.
(A) Methionine degradation. (B) Methionine salvage cycle. (C) Cysteine biosynthesis.
Figure 4.
Figure 4.. PPi-pathway intersection node—Nsp8.
Figure 5.
Figure 5.. PPi-pathway intersection node—Nsp2.
(A) Fatty acid oxidation. (B) Stearate biosynthesis. (C) Vitamin D3 biosynthesis.
Figure 6.
Figure 6.. PPi-pathway intersection node—Nsp4.
Figure 7.
Figure 7.. Pi-pathway intersection nodes - Nsp7 and Orf8a in carbohydrate and fatty acid metabolism.
(A) PPi-pathway intersection node—Nsp7. (B) PPi-Pathway intersection node—Orf8a. (C) PPi-pathway intersection node—Nsp7 and Orf8a.
Figure 8.
Figure 8.. Development of an integrated model of the Human Airway Epithelial cell and SARS-CoV-2.
See this image and copyright information in PMC

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