Coronaviruses (CoVs) typically affect the respiratory tract of mammals, including humans, and lead to mild to severe respiratory tract infections. On March 11, 2020, 2019 novel coronavirus (2019-nCoV/SARS-CoV-2), also known as coronavirus disease 2019 (abbreviated as COVID-19)5, was identified a pandemic by the World Health Organization (WHO). As March 12, 2020, there are over 120,000 people with over 4,500 deaths. However, there are currently no effective medications against 2019-nCoV. There is an urgent need for the development of effective prevention and treatment strategies for 2019-nCoV pandemic. Although investment in biomedical and pharmaceutical research and development has increased significantly over the past two decades, the annual number of new treatments approved by the U.S. Food and Drug Administration (FDA) has remained relatively constant and limited. A recent study estimated that pharmaceutical companies spent $2.6 billion in 2015, up from $802 million in 2003, in th e development of an FDA-approved new chemical entity drug. Drug repurposing, represented as an effective drug discovery strategy from existing drugs, could significantly shorten the time and reduce the cost compared to de novo drug discovery and randomized clinical trials. We recently presented an integrated, network-based methodologies for drug repurposing and drug combinations for potential treatment of 2019-nCoV/SARS-CoV-2 (Zhou et al., Cell Discovery 2020).
In this project, we will present an integrative, 2019-nCoV/SARS-CoV-2 drug repurposing methodology that combines a systems pharmacology-based network medicine platform that quantifies the interplay between the virus-host interactome and drug targets in the human PPI network. The basis for these experiments rests on the notions that (i) the proteins that functionally associate with viral infection (including 2019-nCoV/SARS-CoV-2) are localized in the corresponding subnetwork within the comprehensive human PPI network; and (ii) proteins that serve as drug targets for a specific disease may also be suitable drug targets for potential antiviral infection owing to common PPIs and functional pathways elucidated by the human interactome. We follow this analysis with bioinformatics validation of drug-induced gene signatures and HCoV-induced transcriptomics in human cell lines to inspect the postulated mechanism-of-action in a specific HCoV for which we propose repurposing. This work is done in the Cheng lab, with a solid track record of publications in high impact journals (see references), 2) increasing confidence in scientific rigor and expected healthcare yield; and 2)- Experiments will be utilizing publicly available “omics” databases, so no use of Protected health Information is anticipated, facilitating the “start-up” time.
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