%0 Journal Article
%T Application of the PHENotype SIMulator for rapid identification of potential candidates in effective COVID-19 drug repurposing.
%A Maria NI
%A Rapicavoli RV
%A Alaimo S
%A Bischof E
%A Stasuzzo A
%A Broek JAC
%A Pulvirenti A
%A Mishra B
%A Duits AJ
%A Ferro A
%A  
%J Heliyon
%V 9
%N 3
%D Mar 2023
%M 36911878
%F 3.776
%R 10.1016/j.heliyon.2023.e14115
%X 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.