The IDentif.AI-x pandemic readiness platform: Rapid prioritization of optimized COVID-19 combination therapy regimens
Agata Blasiak, Anh T. L. Truong, Alexandria Remus, Lissa Hooi, Shirley Gek Kheng Seah, Peter Wang, De Hoe Chye, Angeline Lim, Kim Tien Ng, Swee Teng Teo, Yee‐Joo Tan, David Michael Allen, Louis Yi Ann Chai, Wee Joo Chng, Raymond T. P. Lin, David Chien Lye, John Eu-Li Wong, Gek-Yen Gladys Tan, Conrad En Zuo Chan, Edward Kai‐Hua Chow, Dean Ho
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.