Potential COVID-2019 3C-like Protease Inhibitors Designed Using Generative Deep Learning Approaches

Abstract

<div> <div> <p>The emergence of the 2019 novel coronavirus (COVID-19), for which there is no vaccine or any known effective treatment created a sense of urgency for novel drug discovery approaches. One of the most important COVID-19 protein targets is the 3C-like protease for which the crystal structure is known. Most of the immediate efforts are focused on drug repurposing of known clinically-approved drugs and virtual screening for the molecules available from chemical libraries that may not work well. For example, the IC50 of lopinavir, an HIV protease inhibitor, against the 3C-like protease is approximately 50 micromolar, which is far from ideal. In an attempt to address this challenge, on January 28th, 2020 Insilico Medicine decided to utilize a part of its generative chemistry pipeline to design novel drug-like inhibitors of COVID-19 and started generation on January 30th. It utilized three of its previously validated generative chemistry approaches: crystal-derived pocked-based generator, homology modelling-based generation, and ligand-based generation. Novel druglike compounds generated using these approaches were published at <a href="http://www.insilico.com/ncov-sprint/">www.insilico.com/ncov-sprint/</a>. Several molecules will be synthesized and tested using the internal resources; however, the team is seeking collaborations to synthesize, test, and, if needed, optimize the published molecules. <br></p> </div> </div>

Theory about Treatments and Morbidity Prevention of Corona Virus Disease (Covid-19)

“…And it contaminated of most countries in around of the world, and its spread is mostly through the droplets of microbes by patients. This investigate show that importance of combination therapy in contagious microbial diseases [1,10,11].…”

Artificial Intelligence for COVID-19: Rapid Review

“…Integrated AI-based drug discovery methods for novel drug compounds, such as deep generative models, can use large data sets to train and generate new drugs with optimized chemical properties. Such methods are often more time-efficient than traditional computational methods [ 58 ].…”

Artificial Intelligence (AI) and Big Data for Coronavirus (COVID-19) Pandemic: A Survey on the State-of-the-Arts

“…Although findings in this study are currently not clinically approved, they still open new ways to fight the COVID-19 disease. Insilico Medicine in [11] proposed using the deep generative model for drug discovery (which is defined as the process of identifying new medicines). The COVID-19 protease structures generated from the DL model in this work would be further used for computer modeling and simulations for the purpose of obtaining new molecular entity compounds against the COVID-19 coronavirus.…”