Knowledge Graph-Based Approaches to Drug Repurposing for COVID-19

Abstract

The COVID-19 pandemic has motivated researchers all over the world in trying to find effective drugs and therapeutics for treating this disease. To save time, much effort has focused on repurposing drugs known for treating other diseases than COVID-19. To support these drug repurposing efforts, we built the CAS Biomedical Knowledge Graph and identified 1350 small molecules as potentially repurposable drugs that target host proteins and disease processes involved in COVID-19. A computer algorithm-driven drug-ranking method was developed to prioritize those identified small molecules. The top 50 molecules were analyzed according to their molecular functions and included 11 drugs in clinical trials for treating COVID-19 and new candidates that may be of interest for clinical investigation. The CAS Biomedical Knowledge Graph provides researchers an opportunity to accelerate innovation and streamline the investigative process not just for COVID-19 but also in many other diseases.

Network for network concept offers new insights into host- SARS-CoV-2 protein interactions and potential novel targets for developing antiviral drugs

“…During network analysis, each node has multiple scores according to the information importance at that point which includes: degree value (the number of edges of a node), clustering coefficient (represents the density of edges connecting to a node), closeness centrality (how much a node is close to all other nodes), betweenness centrality (how many times a node is on the shortest path between two subnetworks) [ 36 ]. Then, any drug-target attributed data has been integrated into the network to introduce therapeutic biomarker candidates [ 37 ]. Some useful protein-protein interaction databases for network mapping were reviewed by Tanoli et al, 2020 which are (Human Protein Reference Database (HPRD), Biological General Repository for Interaction Datasets (BioGRID), Molecular INTeractiondatabase (MINT), GPS-Prot, Wiki-Pi, Protein Interaction Network Analysis (PINA), MPIDB for the retrieval of interacting genes (STRING), Mammalian protein-protein interaction (MIPS), IntAct, and Database of Interacting Proteins (DIP) [ 25 ].…”

HerbKG: Constructing a Herbal-Molecular Medicine Knowledge Graph Using a Two-Stage Framework Based on Deep Transfer Learning

“…KG-based drug repurposing aims to discover potential drug-target or drug-disease relations that do not currently exist in the KG ( Boudin, 2020 ). Existing efforts have leveraged KGs to identify drugs for the treatment of Covid-19 ( Al-Saleem et al, 2021 ) and rare diseases ( Sosa et al, 2019 ). It is also noted that a drug-disease relation may be either direct or indirect, investigated in ( Zhu et al, 2020 ), where different types of path between a drug and a disease are considered.…”

Best practices for repurposing studies

“…If a compound acts by boosting the immune response, there is not much sense in performing docking studies against viral proteins. Compounds that have appreciable activities and efficacies against a variety of targets (for example, some kinase inhibitors) might work by a mechanism related to their claimed modeof-action [11], but careful studies are required to separate efficacious effects from harmful ones. This requires a careful understanding of whether one is trying to treat the symptoms of the disease [12], or the causative agent itself, the virus.…”