SARS-COV-2 has roused the scientific community with a call to action to combat the growing pandemic. At the time of this writing, there are as yet no novel antiviral agents or approved vaccines available for deployment as a frontline defense. Understanding the pathobiology of COVID-19 could aid scientists in their discovery of potent antivirals by elucidating unexplored viral pathways. One method for accomplishing this is the leveraging of computational methods to discover new candidate drugs and vaccines in silico. In the last decade, machine learning-based models, trained on specific biomolecules, have offered inexpensive and rapid implementation methods for the discovery of effective viral therapies. Given a target biomolecule, these models are capable of predicting inhibitor candidates in a structural-based manner. If enough data are presented to a model, it can aid the search for a drug or vaccine candidate by identifying patterns within the data. In this review, we focus on the recent advances of COVID-19 drug and vaccine development using artificial intelligence and the potential of intelligent training for the discovery of COVID-19 therapeutics. To facilitate applications of deep learning for SARS-COV-2, we highlight multiple molecular targets of COVID-19, inhibition of which may increase patient survival. Moreover, we present CoronaDB-AI, a dataset of compounds, peptides, and epitopes discovered either in silico or in vitro that can be potentially used for training models in order to extract COVID-19 treatment. The information and datasets provided in this review can be used to train deep learning-based models and accelerate the discovery of effective viral therapies.

Deep learning’s automatic feature extraction has proven its superior performance over traditional fingerprint-based features in the implementation of virtual screening models. However, these models face multiple challenges in the field of early drug discovery, such as over-training and generalization to unseen data, due to the inherently unbalanced and small datasets. In this work, the TranScreen pipeline is proposed, which utilizes transfer learning and a collection of weight initializations to overcome these challenges. An amount of 182 graph convolutional neural networks are trained on molecular source datasets and the learned knowledge is transferred to the target task for fine-tuning. The target task of p53-based bioactivity prediction, an important factor for anti-cancer discovery, is chosen to showcase the capability of the pipeline. Having trained a collection of source models, three different approaches are implemented to compare and rank them for a given task before fine-tuning. The results show improvement in performance of the model in multiple cases, with the best model increasing the area under receiver operating curve ROC-AUC from 0.75 to 0.91 and the recall from 0.25 to 1. This improvement is vital for practical virtual screening via lowering the false negatives and demonstrates the potential of transfer learning. The code and pre-trained models are made accessible online.