Network-based multi-omics-disease-drug associations reveal drug repurposing candidates for COVID-19 disease phases

{ 'institution': [{'name': 'ScienceOpen'}], 'indexed': {'date-parts': [[2024, 4, 18]], 'date-time': '2024-04-18T02:13:26Z', 'timestamp': 1713406406464}, 'posted': {'date-parts': [[2024, 4, 16]]}, 'reference-count': 0, 'publisher': 'ScienceOpen', 'license': [ { 'start': { 'date-parts': [[2024, 4, 16]], 'date-time': '2024-04-16T00:00:00Z', 'timestamp': 1713225600000}, 'content-version': 'unspecified', 'delay-in-days': 0, 'URL': 'http://creativecommons.org/licenses/by/4.0/'}], 'funder': [ {'name': 'Dutch Organization of Scientific Research', 'award': ['184.034.019']}, {'name': 'European Union to the EATRIS-Plus infrastructure project', 'award': ['871096']}], 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'abstract': '<jats:p> \n' ' <jats:bold>Background:</jats:bold>The development and roll-out of ' 'vaccines, and the use of various drugs have contributed to controlling the COVID-19 pandemic. ' 'Nevertheless, challenges such as the inequitable distribution of vaccines, the influence of ' 'emerging viral lineages and immune evasive variants on vaccine efficacy, and the inadequate ' 'immune defense in subgroups of the population continue to motivate the development of new ' 'drugs to combat the disease.</jats:p>\n' ' <jats:p> \n' ' <jats:bold>Aim:</jats:bold>In this study, we sought to identify, ' 'prioritize, and characterize drug repurposing candidates appropriate for treating mild, ' 'moderate, or severe COVID-19 using a network-based integrative approach that systematically ' 'integrates drug-related data and multi-omics datasets.</jats:p>\n' ' <jats:p> \n' ' <jats:bold>Methods</jats:bold>: We leveraged drug data, and multi-omics ' 'data, and used a random walk restart algorithm to explore an integrated knowledge graph ' 'comprised of three sub-graphs: (i) a COVID-19 knowledge graph, (ii) a drug repurposing ' 'knowledge graph, and (iii) a COVID-19 disease-state specific omics graph.</jats:p>\n' ' <jats:p> \n' ' <jats:bold>Results:</jats:bold>We prioritized twenty FDA-approved agents ' 'as potential candidate drugs for mild, moderate, and severe COVID-19 disease phases. ' 'Specifically, drugs that could stimulate immune cell recruitment and activation including ' 'histamine, curcumin, and paclitaxel have potential utility in mild disease states to mitigate ' 'disease progression. Drugs like omacetaxine, crizotinib, and vorinostat that exhibit ' 'antiviral properties and have the potential to inhibit viral replication can be considered ' 'for mild to moderate COVID-19 disease states. Also, given the association between antioxidant ' 'deficiency and high inflammatory factors that trigger cytokine storms, antioxidants like ' 'glutathione can be considered for moderate disease states. Drugs that exhibit potent ' 'anti-inflammatory effects like (i) anti-inflammatory drugs (sarilumab and tocilizumab), (ii) ' 'corticosteroids (dexamethasone and hydrocortisone), and (iii) immunosuppressives (sirolimus ' 'and cyclosporine) are potential candidates for moderate to severe disease states that trigger ' 'a hyperinflammatory cascade of COVID-19.</jats:p>\n' ' <jats:p> \n' ' <jats:bold>Conclusion:</jats:bold>Our study demonstrates that the ' 'multi-omics data-driven integrative analysis within the drug data enables prioritizing drug ' 'candidates for COVID-19 disease phases, offering a comprehensive basis for therapeutic ' 'strategies that can be brought to market quickly given their established safety profiles. ' 'Importantly, the multi-omics data-driven integrative analysis within the drug data approach ' 'implemented here can be used to prioritize drug repurposing candidates appropriate for other ' 'diseases.</jats:p>', 'DOI': '10.58647/drugarxiv.pr000010.v1', 'type': 'posted-content', 'created': {'date-parts': [[2024, 4, 17]], 'date-time': '2024-04-17T13:50:17Z', 'timestamp': 1713361817000}, 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Network-based multi-omics-disease-drug associations reveal drug repurposing candidates for ' 'COVID-19 disease phases', 'prefix': '10.58647', 'author': [ { 'ORCID': 'http://orcid.org/0000-0002-2980-1392', 'authenticated-orcid': False, 'given': 'Francis Edem', 'family': 'Agamah', 'sequence': 'first', 'affiliation': [ { 'id': [ { 'id': 'https://ror.org/03p74gp79', 'id-type': 'ROR', 'asserted-by': 'publisher'}], 'name': 'Computational Biology Division, Department of Integrative ' 'Biomedical Sciences, Institute of Infectious Disease and ' 'Molecular Medicine, Faculty of Health Sciences, University of ' 'Cape Town, Cape Town, South Africa'}]}, { 'given': 'Thomas H.A.', 'family': 'Ederveen', 'sequence': 'additional', 'affiliation': [ { 'id': [ { 'id': 'https://ror.org/05wg1m734', 'id-type': 'ROR', 'asserted-by': 'publisher'}], 'name': 'Department of Medical BioSciences, Radboud University Medical ' 'Center Nijmegen, The Netherlands'}]}, { 'given': 'Michelle', 'family': 'Skelton', 'sequence': 'additional', 'affiliation': [ { 'id': [ { 'id': 'https://ror.org/03p74gp79', 'id-type': 'ROR', 'asserted-by': 'publisher'}], 'name': 'Computational Biology Division, Department of Integrative ' 'Biomedical Sciences, Institute of Infectious Disease and ' 'Molecular Medicine, Faculty of Health Sciences, University of ' 'Cape Town, Cape Town, South Africa'}]}, { 'given': 'Darren P.', 'family': 'Martin', 'sequence': 'additional', 'affiliation': [ { 'id': [ { 'id': 'https://ror.org/03p74gp79', 'id-type': 'ROR', 'asserted-by': 'publisher'}], 'name': 'Computational Biology Division, Department of Integrative ' 'Biomedical Sciences, Institute of Infectious Disease and ' 'Molecular Medicine, Faculty of Health Sciences, University of ' 'Cape Town, Cape Town, South Africa'}]}, { 'given': 'Emile R.', 'family': 'Chimusa', 'sequence': 'additional', 'affiliation': [ { 'id': [ { 'id': 'https://ror.org/049e6bc10', 'id-type': 'ROR', 'asserted-by': 'publisher'}], 'name': 'Department of Applied Science, Faculty of Health and Life ' 'Sciences, Northumbria University, Newcastle, Tyne and Wear, NE1 ' '8ST, UK'}]}, { 'given': "Peter A.C. 't Hoen", 'family': "'t Hoen", 'sequence': 'additional', 'affiliation': [ { 'id': [ { 'id': 'https://ror.org/05wg1m734', 'id-type': 'ROR', 'asserted-by': 'publisher'}], 'name': 'Department of Medical BioSciences, Radboud University Medical ' 'Center Nijmegen, The Netherlands'}]}], 'member': '5403', 'container-title': [], 'original-title': [], 'link': [ { 'URL': 'https://drugrepocentral.scienceopen.com/hosted-document?doi=10.58647/DRUGARXIV.PR000010.v1', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2024, 4, 17]], 'date-time': '2024-04-17T13:50:18Z', 'timestamp': 1713361818000}, 'score': 1, 'resource': { 'primary': { 'URL': 'https://drugrepocentral.scienceopen.com/hosted-document?doi=10.58647/DRUGARXIV.PR000010.v1'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2024, 4, 16]]}, 'references-count': 0, 'URL': 'http://dx.doi.org/10.58647/DRUGARXIV.PR000010.v1', 'relation': {}, 'subject': [], 'published': {'date-parts': [[2024, 4, 16]]}, 'subtype': 'preprint'}