Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 29 April 2021 / Approved: 30 April 2021 / Online: 30 April 2021 (15:14:06 CEST)

A peer-reviewed article of this Preprint also exists.

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. 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.

Journal reference: Genes 2021, 12, 796
DOI: 10.3390/genes12060796

Abstract

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 are not effective anymore. 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 and B.1.351. 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.

Subject Areas

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

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