Baricitinib as potential treatment for 2019-nCoV acute respiratory disease
Richardson, P., Griffin, I., Tucker, C., Smith, D., Oechsle, O., Phelan, A., & Stebbing, J. (2020). Baricitinib as potential treatment for 2019-nCoV acute respiratory disease . The Lancet, 395(10223), e30–e31.
Review written by:
Lily Xu, edited by
Yellow - The authors are current employees of BenevolentAI and include a former advisory board member. This Correspondence was submitted to the Lancet to assist in the global response to the SARS-CoV-2 pandemic.
The rapid spread of the 2019 novel coronavirus (2019-nCoV) and acute respiratory disease brought on by infection has caused a great demand for effective treatments prior to the developments of a vaccine. Richardson et al. used the BenevolentAIplatform to search for approved drugs that might block viral infection. BenevolentAI, is a machine learning generated platform that builds knowledge graphs based on information extracted from scientific research literature as well as other information sources to create a repository of structured medical information.
One current hypothesis for SARS-CoV-2 entry into cells is through ACE2 receptor-mediated endocytosis. It is hypothesized that 2019-nCoV enters the lung AT2 alveolar epithelial cells. One of the known regulators of endocytosis is AP2-associated protein kinase 1 (AAK1), so disrupting AAK1 could block the viral passage into the cells and interrupt intracellular virus assembly. Of 378 AAK1 inhibitors identified using BenevolentAI, the authors found six high affinity AAK1 inhibitors. The authors recommend Baricitinib for clinical trials due to its side effect profile and a second mechanism of action, binding cyclin G-associated kinase, another mediator involved in endocytosis regulation. Baricitinib requires relatively low plasma concentrations to see therapeutic effects and other candidates have known serious side-effects. Richardson et al. propose Baricitinib be trialled with a patient population with 2019-nCoV acute respiratory disease to examine the drug’s effect on viral entry and lung inflammation.