Predicting novel drug candidates against Covid-19 using generative deep neural networks

Amilpur, Santhosh; Bhukya, Raju

The novel Coronavirus outbreak has created a massive economic crisis, and many succumb to death, disturbing the lives of mankind all over the world. Currently, there are no viable treatment for this condition, drug development approaches are being pursued with vigor. The major treatment options are to repurpose existing drugs or to find new ones. Traditional methods for drug discovery take a longer time, so there is an urgent need to develop some alternative techniques that reduces search space for drug candidates. Towards this endeavor, we propose a novel drug discovery method that leverages on long short term memory (LSTM) model to generate novel molecules that are adept at binding with novel Coronavirus protease. Our study demonstrates that the proposed method is able to recreate novel molecules that correlate very much with the properties of trained molecules. Further, we fine-tune the model to generate novel drug-like molecules that are active towards a specific target. We consider 3CLPro, the main protease of novel Coronavirus, as a therapeutic target and demonstrated in silico screening to assess target structural binding affinities with docking simulations. We observed that 80% of generated molecules show docking free energy of less than −5.8 kcal/mol. The top generated drug candidate has the highest binding affinity with a docking score of −8.5 kcal/mol, which is very much lower when compared to approved existing commercial drugs including, Remdesivir. The low binding energy indicates that the generated molecules could be explored as potential drug candidates for Covid-19.