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Article

Genome-Scale Metabolic Model of Infection with SARS-CoV-2 Mutants Confirms Guanylate Kinase as Robust Potential Antiviral Target

1
Department of Computer Science, University of Tübingen, 72076 Tübingen, Germany
2
Cluster of Excellence ‘Controlling Microbes to Fight Infections’, University of Tübingen, 72076 Tübingen, Germany
3
Computational Systems Biology of Infections and Antimicrobial-Resistant Pathogens, Institute for Bioinformatics and Medical Informatics (IBMI), University of Tübingen, 72076 Tübingen, Germany
4
Bernhard Nocht Institute for Tropical Medicine, Virus Immunology, 20359 Hamburg, Germany
5
German Center for Infection Research (DZIF), Partner Site Tübingen, 72076 Tübingen, Germany
*
Author to whom correspondence should be addressed.
Academic Editors: Giuseppe Novelli and Michela Biancolella
Genes 2021, 12(6), 796; https://doi.org/10.3390/genes12060796
Received: 29 April 2021 / Revised: 19 May 2021 / Accepted: 21 May 2021 / Published: 24 May 2021
(This article belongs to the Special Issue COVID-19 and Molecular Genetics)
The current SARS-CoV-2 pandemic is still threatening humankind. Despite first successes in vaccine development and approval, no antiviral treatment is available for COVID-19 patients. The success is further tarnished by the emergence and spreading of mutation variants of SARS-CoV-2, for which some vaccines have lower efficacy. This highlights the urgent need for antiviral therapies even more. This article describes how the genome-scale metabolic model (GEM) of the host-virus interaction of human alveolar macrophages and SARS-CoV-2 was refined by incorporating the latest information about the virus’s structural proteins and the mutant variants B.1.1.7, B.1.351, B.1.28, B.1.427/B.1.429, and B.1.617. We confirmed the initially identified guanylate kinase as a potential antiviral target with this refined model and identified further potential targets from the purine and pyrimidine metabolism. The model was further extended by incorporating the virus’ lipid requirements. This opened new perspectives for potential antiviral targets in the altered lipid metabolism. Especially the phosphatidylcholine biosynthesis seems to play a pivotal role in viral replication. The guanylate kinase is even a robust target in all investigated mutation variants currently spreading worldwide. These new insights can guide laboratory experiments for the validation of identified potential antiviral targets. Only the combination of vaccines and antiviral therapies will effectively defeat this ongoing pandemic. View Full-Text
Keywords: SARS-CoV-2; COVID-19; flux balance analysis (FBA); genome-scale metabolic models; target identification; reaction knock-out; structural proteins; purine metabolism; pyrimidine metabolism; B.1.1.7; B.1.351; B.1.617; B.1.28; B.1.427/B.1.429 SARS-CoV-2; COVID-19; flux balance analysis (FBA); genome-scale metabolic models; target identification; reaction knock-out; structural proteins; purine metabolism; pyrimidine metabolism; B.1.1.7; B.1.351; B.1.617; B.1.28; B.1.427/B.1.429
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MDPI and ACS Style

Renz , A.; Widerspick , L.; Dräger , A. Genome-Scale Metabolic Model of Infection with SARS-CoV-2 Mutants Confirms Guanylate Kinase as Robust Potential Antiviral Target. Genes 2021, 12, 796. https://doi.org/10.3390/genes12060796

AMA Style

Renz  A, Widerspick  L, Dräger  A. Genome-Scale Metabolic Model of Infection with SARS-CoV-2 Mutants Confirms Guanylate Kinase as Robust Potential Antiviral Target. Genes. 2021; 12(6):796. https://doi.org/10.3390/genes12060796

Chicago/Turabian Style

Renz , Alina, Lina Widerspick , and Andreas Dräger . 2021. "Genome-Scale Metabolic Model of Infection with SARS-CoV-2 Mutants Confirms Guanylate Kinase as Robust Potential Antiviral Target" Genes 12, no. 6: 796. https://doi.org/10.3390/genes12060796

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