Viral pandemic preparedness: A pluripotent stem cell-based machine-learning platform for simulating SARS-CoV-2 infection to enable drug discovery and repurposing

Abstract

Infection with the SARS-CoV-2 virus has rapidly become a global pandemic for which we were not prepared. Several clinical trials using previously approved drugs and drug combinations are urgently under way to improve the current situation. A vaccine option has only recently become available, but worldwide distribution is still a challenge. It is imperative that, for future viral pandemic preparedness, we have a rapid screening technology for drug discovery and repurposing. The primary purpose of this research project was to evaluate the DeepNEU stem-cell based platform by creating and validating computer simulations of artificial lung cells infected with SARS-CoV-2 to enable the rapid identification of antiviral therapeutic targets and drug repurposing. The data generated from this project indicate that (a) human alveolar type lung cells can be simulated by DeepNEU (v5.0), (b) these simulated cells can then be infected with simulated SARS-CoV-2 virus, (c) the unsupervised learning system performed well in all simulations based on available published wet lab data, and (d) the platform identified potentially effective anti-SARS-CoV2 combinations of known drugs for urgent clinical study. The data also suggest that DeepNEU can identify potential therapeutic targets for expedited vaccine development. We conclude that based on published data plus current DeepNEU results, continued development of the DeepNEU platform will improve our preparedness for and response to future viral outbreaks. This can be achieved through rapid identification of potential therapeutic options for clinical testing as soon as the viral genome has been confirmed.