# PaccMannRL on SARS-CoV-2: Designing antiviral candidates with conditional generative models

arXiv: https://arxiv.org/abs/2005.13285 · HTML: https://mlsanity.com/paper/2005.13285/

## Key facts

- Cited by 3 papers in the map (data through 14 Oct 2026).
- First posted on arXiv 27 May 2020.

## Built on by (most cited first, 3 of 3)

- [De novo design of protein target specific scaffold-based Inhibitors via Reinforcement Learning](https://mlsanity.com/paper/2205.10473/) (2022)
- [Benchmarking Deep Graph Generative Models for Optimizing New Drug Molecules for COVID-19](https://mlsanity.com/paper/2102.04977/) (2021)
- [Evening the Score: Targeting SARS-CoV-2 Protease Inhibition in Graph Generative Models for Therapeutic Candidates](https://mlsanity.com/paper/2105.10489/) (2021)

## Abstract (arXiv)

With the fast development of COVID-19 into a global pandemic, scientists around the globe are desperately searching for effective antiviral therapeutic agents. Bridging systems biology and drug discovery, we propose a deep learning framework for conditional de novo design of antiviral candidate drugs tailored against given protein targets. First, we train a multimodal ligand--protein binding affinity model on predicting affinities of antiviral compounds to target proteins and couple this model with pharmacological toxicity predictors. Exploiting this multi-objective as a reward function of a conditional molecular generator (consisting of two VAEs), we showcase a framework that navigates the chemical space toward regions with more antiviral molecules. Specifically, we explore a challenging setting of generating ligands against unseen protein targets by performing a leave-one-out-cross-validation on 41 SARS-CoV-2-related target proteins. Using deep RL, it is demonstrated that in 35 out of 41 cases, the generation is biased towards sampling more binding ligands, with an average increase of 83% comparing to an unbiased VAE. We present a case-study on a potential Envelope-protein inhibitor and perform a synthetic accessibility assessment of the best generated molecules is performed that resembles a viable roadmap towards a rapid in-vitro evaluation of potential SARS-CoV-2 inhibitors.