Drug repurposing for COVID-19 using graph neural network and harmonizing multiple evidence

TL;DR

This study presents a comprehensive drug repurposing pipeline for COVID-19 that integrates biological interactions, deep graph neural networks, and multi-level validation to identify promising therapeutic candidates.

Contribution

It introduces a novel approach combining a SARS-CoV-2 knowledge graph with deep graph neural networks and validation methods to prioritize repurposable drugs for COVID-19.

Findings

Identified top 22 candidate drugs including Azithromycin and Atorvastatin.

Pinpointed drug combinations with potential synergistic effects.

Validated candidate drugs through genetic, in vitro, and electronic health record analyses.

Abstract

Amid the pandemic of 2019 novel coronavirus disease (COVID-19) infected by SARS-CoV-2, a vast amount of drug research for prevention and treatment has been quickly conducted, but these efforts have been unsuccessful thus far. Our objective is to prioritize repurposable drugs using a drug repurposing pipeline that systematically integrates multiple SARS-CoV-2 and drug interactions, deep graph neural networks, and in-vitro/population-based validations. We first collected all the available drugs (n= 3,635) involved in COVID-19 patient treatment through CTDbase. We built a SARS-CoV-2 knowledge graph based on the interactions among virus baits, host genes, pathways, drugs, and phenotypes. A deep graph neural network approach was used to derive the candidate representation based on the biological interactions. We prioritized the candidate drugs using clinical trial history, and then validated them with their genetic profiles, in vitro experimental efficacy, and electronic health records. We highlight the top 22 drugs including Azithromycin, Atorvastatin, Aspirin, Acetaminophen, and Albuterol. We further pinpointed drug combinations that may synergistically target COVID-19. In summary, we demonstrated that the integration of extensive interactions, deep neural networks, and rigorous validation can facilitate the rapid identification of candidate drugs for COVID-19 treatment. This is a post-peer-review, pre-copyedit version of an article published in Scientific Reports The final authenticated version is available online at: https://www.nature.com/articles/s41598-021-02353-5