Application of the PHENotype SIMulator for rapid identification of potential candidates in effective COVID-19 drug repurposing

Autor: Naomi I. Maria, Rosaria Valentina Rapicavoli, Salvatore Alaimo, Evelyne Bischof, Alessia Stasuzzo, Jantine A.C. Broek, Alfredo Pulvirenti, Bud Mishra, Ashley J. Duits, Alfredo Ferro
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Heliyon, Vol 9, Iss 3, Pp e14115- (2023)
Druh dokumentu: article
ISSN: 2405-8440
DOI: 10.1016/j.heliyon.2023.e14115
Popis: The current, rapidly diversifying pandemic has accelerated the need for efficient and effective identification of potential drug candidates for COVID-19. Knowledge on host-immune response to SARS-CoV-2 infection, however, remains limited with few drugs approved to date. Viable strategies and tools are rapidly arising to address this, especially with repurposing of existing drugs offering significant promise. Here we introduce a systems biology tool, the PHENotype SIMulator, which -by leveraging available transcriptomic and proteomic databases-allows modeling of SARS-CoV-2 infection in host cells in silico to i) determine with high sensitivity and specificity (both>96%) the viral effects on cellular host-immune response, resulting in specific cellular SARS-CoV-2 signatures and ii) utilize these cell-specific signatures to identify promising repurposable therapeutics. Powered by this tool, coupled with domain expertise, we identify several potential COVID-19 drugs including methylprednisolone and metformin, and further discern key cellular SARS-CoV-2-affected pathways as potential druggable targets in COVID-19 pathogenesis.
Databáze: Directory of Open Access Journals