<p>Recent studies have been demonstrated that
the excessive inflammatory response is an important factor of death in COVID-19
patients. In this study, we proposed a network representation learning-based
methodology, termed AIdrug2cov, to discover drug mechanism and
anti-inflammatory response for patients with COVID-19. This work explores the
multi-hub characteristic of a heterogeneous drug network integrating 8 unique
networks. Inspired by the multi-hub characteristic, we design three billion
special meta paths to train a deep representation model for learning
low-dimensional vectors that integrate long-range structure dependency and
complex semantic relation among network nodes. Using the representation
vectors, AIdrug2cov identifies 40 potential targets and 22 high-confidence
drugs that bind to tumor necrosis factor(TNF)-α or interleukin(IL)-6 to prevent excessive
inflammatory responses in COVID-19 patients. Finally, we analyze mechanisms of
action based on PubMed publications and ongoing clinical trials, and explore
the possible binding modes between the new predicted drugs and targets via
docking program. In addition, the results in 5 pharmacological application suggested
that AIdrug2cov significantly outperforms 5 other state-of-the-art network
representation approaches, future demonstrating the availability of AIdrug2cov
in drug development field. In summary, AIdrug2cov is practically useful for
accelerating COVID-19 therapeutic development. The source code and data can be
downloaded from https://github.com/pengsl-lab/AIdrug2cov.git.</p>