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- Title
The IDentif.AI-x pandemic readiness platform: Rapid prioritization of optimized COVID-19 combination therapy regimens.
- Authors
Blasiak, Agata; Truong, Anh T. L.; Remus, Alexandria; Hooi, Lissa; Seah, Shirley Gek Kheng; Wang, Peter; Chye, De Hoe; Lim, Angeline Pei Chiew; Ng, Kim Tien; Teo, Swee Teng; Tan, Yee-Joo; Allen, David Michael; Chai, Louis Yi Ann; Chng, Wee Joo; Lin, Raymond T. P.; Lye, David C. B.; Wong, John Eu-Li; Tan, Gek-Yen Gladys; Chan, Conrad En Zuo; Chow, Edward Kai-Hua
- Abstract
IDentif.AI-x, a clinically actionable artificial intelligence platform, was used to rapidly pinpoint and prioritize optimal combination therapies against COVID-19 by pairing a prospective, experimental validation of multi-drug efficacy on a SARS-CoV-2 live virus and Vero E6 assay with a quadratic optimization workflow. A starting pool of 12 candidate drugs developed in collaboration with a community of infectious disease clinicians was first narrowed down to a six-drug pool and then interrogated in 50 combination regimens at three dosing levels per drug, representing 729 possible combinations. IDentif.AI-x revealed EIDD-1931 to be a strong candidate upon which multiple drug combinations can be derived, and pinpointed a number of clinically actionable drug interactions, which were further reconfirmed in SARS-CoV-2 variants B.1.351 (Beta) and B.1.617.2 (Delta). IDentif.AI-x prioritized promising drug combinations for clinical translation and can be immediately adjusted and re-executed with a new pool of promising therapies in an actionable path towards rapidly optimizing combination therapy following pandemic emergence.
- Subjects
EXPERIMENTAL design; COVID-19; COMBINATION drug therapy; CELL culture; ARTIFICIAL intelligence; IMMUNOMODULATORS; EMERGENCY management; DOSE-effect relationship in pharmacology; DRUG interactions; CELL surface antigens; COVID-19 pandemic; IMMUNODIAGNOSIS
- Publication
NPJ Digital Medicine, 2022, Vol 5, Issue 1, p1
- ISSN
2398-6352
- Publication type
Article
- DOI
10.1038/s41746-022-00627-4