Genome-Scale Metabolic Model of Infection with SARS-CoV-2 Mutants Confirms Guanylate Kinase as Robust Potential Antiviral Target.
Genes (Basel)
; 12(6)2021 05 24.
Article
in English
| MEDLINE | ID: covidwho-1243973
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 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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Genome, Viral
/
Energy Metabolism
/
Guanylate Kinases
/
Host-Pathogen Interactions
/
SARS-CoV-2
/
COVID-19
/
Mutation
Type of study:
Prognostic study
Topics:
Vaccines
/
Variants
Limits:
Humans
Language:
English
Year:
2021
Document Type:
Article
Affiliation country:
Genes12060796
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