key: cord-0923839-2cx5x55y authors: Mangione, William; Falls, Zackary; Melendy, Thomas; Chopra, Gaurav; Samudrala, Ram title: Shotgun drug repurposing biotechnology to tackle epidemics and pandemics date: 2020-05-13 journal: Drug Discov Today DOI: 10.1016/j.drudis.2020.05.002 sha: 9ed7274c8048ab96ca7b6369bacd9c3228d92125 doc_id: 923839 cord_uid: 2cx5x55y nan This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. We used the CANDO platform to generate putative drug repurposing candidates against SARS-CoV-2 ( Figure 1) . The platform ranks a number of clinical trial candidates listed in Table 1 of Harrison [9] in the top 1% of predictions and provides relevant target and off-target interaction information for them. We are currently in the process of undertaking in vitro validation of top ranked candidates as well as using EHR data to corroborate or negate predictions made by the platform. This pandemic highlights the importance of developing such robust shotgun repurposing platforms that not only make drug discovery more efficient by systematically evaluating multiple uses of a human ingestible drug but may also be rapidly deployed every time a new disease arises. Three coronavirus outbreaks in two decades, including the current pandemic, indicates a necessity of preparation for the next one that may be more deadly and costly. The CANDO drug repurposing platform was originally funded and implemented for predicting drug leads for epidemics and pandemics. Sustained funding for shotgun drug repurposing biotechnology that have been benchmarked extensively to identify potential drugs for all diseases, such as CANDO, will prepare us for this eventuality while also providing us with an array of therapeutic solutions to help improve human health and quality of life. WM, ZF, and RS conceived and implemented all data analysis. WM, ZF, and RS wrote the manuscript. ZF generated the docking images. TM directed the prodrug analysis and provided expert opinion on antiviral drugs. GC substantially edited the manuscript. The authors declare no conflicts of interest. host-based mechanism since no viral proteins are predicted to be strongly targeted. All of the highlighted candidates have been shown or are believed to have activity against SARS-CoV-2 and/or are undergoing clinical trials to demonstrate efficacy [9] . Additionally, the drugs at rank 1 and 14 (omacetaxine mepesuccinate and mycophenolate mofetil, not shown) were previously identified in experimental assays to be potent inhibitors of coronaviruses [10, 11] . Therefore, the other higher ranked drugs in our lists are also worth evaluating, with the potential payoff of choice, greater efficacy, and reduced cost for compassionate off-label use and/or in clinical trials. Shotgun repurposing platforms such as CANDO not only generates short lists of therapeutic candidates rapidly but may also provide mechanistic atomic level detail of relevant interactions between targets and repurposable drugs identified by us or by any other means (including serendipity and analysis of medical records). CANDO and the infinite drug discovery frontier. Drug discovery today Combating ebola with repurposed therapeutics using the CANDO platform Systems biology-based investigation of cellular antiviral drug targets identified by gene-trap insertional mutagenesis A new computational drug repurposing method using established disease-drug pair knowledge Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2 A SARS-CoV-2 protein interaction map reveals targets for drug repurposing cando.py: Open source software for predictive bioanalytics of large scale drug-protein-disease data. bioRxiv CANDOCK: Chemical atomic network based hierarchical flexible docking algorithm using generalized statistical potentials Coronavirus puts drug repurposing on the fast track High-throughput screening and identification of potent broad-spectrum inhibitors of coronaviruses Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection J o u r n a l P r e -p r o o f