SperoPredictor: An Integrated Machine Learning and Molecular Docking-Based Drug Repurposing Framework With Use Case of COVID-19.

The global spread of the SARS coronavirus 2 (SARS-CoV-2), its manifestation in human hosts as a contagious disease, and its variants have induced a pandemic resulting in the deaths of over 6,000,000 people. Extensive efforts have been devoted to drug research to cure and refrain the spread of COVID-19, but only one drug has received FDA approval yet. Traditional drug discovery is inefficient, costly, and unable to react to pandemic threats. Drug repurposing represents an effective strategy for drug discovery and reduces the time and cost compared to de novo drug discovery. In this study, a generic drug repurposing framework (SperoPredictor) has been developed which systematically integrates the various types of drugs and disease data and takes the advantage of machine learning (Random Forest, Tree Ensemble, and Gradient Boosted Trees) to repurpose potential drug candidates against any disease of interest. Drug and disease data for FDA-approved drugs (n = 2,865), containing four drug features and three disease features, were collected from chemical and biological databases and integrated with the form of drug-disease association tables. The resulting dataset was split into 70% for training, 15% for testing, and the remaining 15% for validation. The testing and validation accuracies of the models were 99.3% for Random Forest and 99.03% for Tree Ensemble. In practice, SperoPredictor identified 25 potential drug candidates against 6 human host-target proteomes identified from a systematic review of journals. Literature-based validation indicated 12 of 25 predicted drugs (48%) have been already used for COVID-19 followed by molecular docking and re-docking which indicated 4 of 13 drugs (30%) as potential candidates against COVID-19 to be pre-clinically and clinically validated. Finally, SperoPredictor results illustrated the ability of the platform to be rapidly deployed to repurpose the drugs as a rapid response to emergent situations (like COVID-19 and other pandemics).

SperoPredictor: An Integrated Machine Learning and Molecular Docking-Based Drug Repurposing Framework With Use Case of COVID-19

Illustration of SperoPredictor repurposing framework. It starts with data collection followed by machine learning models training, model deployment, literature, and molecular docking-based validation.

A comprehensive review of artificial intelligence and network based approaches to drug repurposing in Covid-19.

Conventional drug discovery and development is tedious and time-taking process; because of which it has failed to keep the required pace to mitigate threats and cater demands of viral and re-occurring diseases, such as Covid-19. The main reasons of this delay in traditional drug development are: high attrition rates, extensive time requirements, and huge financial investment with significant risk. The effective solution to de novo drug discovery is drug repurposing. Previous studies have shown that the network-based approaches and analysis are versatile platform for repurposing as the network biology is used to model the interactions between variety of biological concepts. Herein, we provide a comprehensive background of machine learning and deep learning in drug repurposing while specifically focusing on the applications of network-based approach to drug repurposing in Covid-19, data sources, and tools used. Furthermore, use of network proximity, network diffusion, and AI on network-based drug repurposing for Covid-19 is well-explained. Finally, limitations of network-based approaches in general and specific to network are stated along with future recommendations for better network-based models.