24 Jun 2020

EMBO MOLECULAR MEDICINE

Following confirmation in April that a potential treatment for COVID-19 identified by BenevolentAI has entered clinical trials, further detail on the data supporting the AI-derived hypothesis and early results from clinical testing have been published in the European Molecular Biology Organization Molecular Medicine Journal.

A paper co-authored by Eli Lilly, BenevolentAI, Imperial College, National University of Singapore, the Karolinksa Institute and Milan, has been published in the European Molecular Biology Organization (EMBO) Molecular Medicine Journal. The publication (doi:10.15252/emmm.202012697) provides further detail on the data supporting the decision to move baricitinib, an approved treatment for rheumatoid arthritis developed by Eli Lilly and Incyte, into clinical testing in hospitalized patients diagnosed with COVID-19.

In exploring potential treatment options for COVID-19, our team focused on already approved medicines that could be ready for large-scale trials within weeks. Rather than focusing solely on drugs that could affect the virus directly, the team explored ways to inhibit the cellular processes that the virus uses to infect human cells. The aim was to identify existing medicines that could potentially stop the progression of COVID-19, inhibit the “cytokine storm” (an overreaction of the body’s immune system) and reduce the inflammatory damage associated with this disease. 

Anti-cytokine activity for baricitinib

As set out in the paper published in EMBO Mol Med, the anti-cytokine and anti-inflammatory activity of baricitinib was evaluated with a focus on cytokines relevant to COVID-19 infection. Cytokines are proteins released by cells in the body, including immune cells where they coordinate the response against an infection and cause inflammation. We used our proprietary Knowledge Graph to identify medicines capable of both inhibiting virus infectivity and the action of cytokines, thus reducing the effects of the “cytokine storm”. 

Anti-viral activity for baricitinib

Our research showed that, based on existing rheumatoid arthritis data, baricitinib demonstrates inhibitory activity against the kinases (enzymes) that are believed to support the entry of the coronavirus into lung epithelial cells (cells that line the surfaces of the body).

Early clinical use of baricitinib in COVID-19 patients

Following publication of our findings in The Lancet and The Lancet Infectious Diseases in February, COVID-19 patients were treated with baricitinib in a pilot study in Milan, Italy. Four patients with bilateral COVID-19 pneumonia, who presented with varying degrees of disease severity were included in the study. When treated with baricitinib, all four patients showed improvement in symptoms including cough, fever, and reduction in the COVID-19 viral load.


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