Evening the Score: Targeting SARS-CoV-2 Protease Inhibition in Graph Generative Models for Therapeutic Candidates

We examine a pair of graph generative models for the therapeutic design of novel drug candidates targeting SARS-CoV-2 viral proteins. Due to a sense of urgency, we chose well-validated models with unique strengths: an autoencoder that generates molecules with similar structures to a dataset of drugs with anti-SARS activity and a reinforcement learning algorithm that generates highly novel molecules. During generation, we explore optimization toward several design targets to balance druglikeness, synthetic accessability, and anti-SARS activity based on IC50. This generative framework1 will accelerate drug discovery in future pandemics through the high-throughput generation of targeted therapeutic candidates.

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