{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T04:01:47Z","timestamp":1791000107968,"version":"4.1.0"},"reference-count":76,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T00:00:00Z","timestamp":1621814400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["EXC 2124 - 390838134"],"award-info":[{"award-number":["EXC 2124 - 390838134"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009139","name":"Deutsches Zentrum f\u00fcr Infektionsforschung","doi-asserted-by":"publisher","award":["8020708703"],"award-info":[{"award-number":["8020708703"]}],"id":[{"id":"10.13039\/100009139","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>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\u2019s 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\u2019 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.<\/jats:p>","DOI":"10.3390\/genes12060796","type":"journal-article","created":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T12:38:01Z","timestamp":1621859881000},"page":"796","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Genome-Scale Metabolic Model of Infection with SARS-CoV-2 Mutants Confirms Guanylate Kinase as Robust Potential Antiviral Target"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3851-9978","authenticated-orcid":false,"given":"Alina","family":"Renz\u00a0","sequence":"first","affiliation":[{"name":"Department of Computer Science, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Cluster of Excellence \u2018Controlling Microbes to Fight Infections\u2019, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Computational Systems Biology of Infections and Antimicrobial-Resistant Pathogens, Institute for Bioinformatics and Medical Informatics (IBMI), University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6666-7770","authenticated-orcid":false,"given":"Lina","family":"Widerspick\u00a0","sequence":"additional","affiliation":[{"name":"Bernhard Nocht Institute for Tropical Medicine, Virus Immunology, 20359 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1240-5553","authenticated-orcid":false,"given":"Andreas","family":"Dr\u00e4ger\u00a0","sequence":"additional","affiliation":[{"name":"Department of Computer Science, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Cluster of Excellence \u2018Controlling Microbes to Fight Infections\u2019, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Computational Systems Biology of Infections and Antimicrobial-Resistant Pathogens, Institute for Bioinformatics and Medical Informatics (IBMI), University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41586-020-2012-7","article-title":"A pneumonia outbreak associated with a new coronavirus of probable bat origin","volume":"579","author":"Zhou","year":"2020","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"111518","DOI":"10.1016\/j.biopha.2021.111518","article-title":"Potential therapeutic agents to COVID-19: An update review on antiviral therapy, immunotherapy, and cell therapy","volume":"138","author":"Mirtaleb","year":"2021","journal-title":"Biomed. 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