Eli Lilly’s Olumiant (ingredient: baricitinib) is likely to become the second Covid-19 treatment after Gilead Sciences’ remdesivir, industry officials said.

Earlier this year, British researchers used artificial intelligence (AI) to discover that Olumiant had the highest potential among authorized medicines to fight against Covid-19.

On Monday, Lilly announced that its Janus kinase (JAK) inhibitor Olumiant, in combination with Gilead’s remdesivir, shortened the treatment period in the ACTT-2 clinical trial.

​Viral entry via clathrin-mediated endocytosis (Source: Lancet Infect Dis 2020; published online Feb 27. https://doi.org/10.1016/S1473-3099(20)30132-8.)​
​Viral entry via clathrin-mediated endocytosis (Source: Lancet Infect Dis 2020; published online Feb 27. https://doi.org/10.1016/S1473-3099(20)30132-8.)​

The ACTT-2 study, sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the U.S. National Institutes of Health (NIH), is one of the trials to develop a Covid-19 treatment.

The study compared Olumiant plus the first Covid-19 treatment remdesivir, with remdesivir alone. The results showed that the combo treatment group had a one-day reduction in median recovery time, compared to those treated with remdesivir.

“This finding was statistically significant,” Lilly said, adding that it would file for emergency use authorization (EUA) with the U.S. Food and Drug Administration and seek approval of the health authorities in other countries for Olumiant as a Covid-19 treatment.

Olumiant is a JAK-1/2 inhibitor to treat rheumatoid arthritis but an AI-based platform discovered that Olumiant could become a potential Covid-19 treatment candidate.

It was late 2019 when the first case of a new coronavirus was reported. In less than two months since Chinese scientists shared the isolated genes of the Covid-19 virus in a global database, British researchers used AI to recommend Olumiant as the most promising Covid-19 treatment.

Professor Justin Stebbing of Imperial College London published his joint study with AI start-up firm BenevolentAI on Olumiant in Correspondence to the Lancet on Feb. 4.

In the study, Stebbing said BenevolentAI’s AI-based algorithm searched for suitable drugs for Covid-19 treatment among existing medicines and picked Olumiant as the strongest candidate.

The research team focused on “receptor-mediated endocytosis” that occurs when most viruses penetrate human cells.

At the time, the NIAID and researchers of the University of Texas at Austin (UT) identified the structure of proteins, called “spikes,” on the surface of the Covid-19 virus. They assumed that these spikes bind to ACE2 on the surface of human cells to start the viral penetration.

Under the assumption that inhibiting AP2-associated protein kinase 1 (AAK1), which promotes ACE2’s endocytosis, could prevent the viral entry, the researchers used AI to search for drugs with high affinity for AAK1 among authorized medicines.

The AI-based algorithm found 378 AAK1 inhibitors, and the researchers narrowed them down based on affinity for AAK1 and toxicity. As a result, Olumiant was the most suitable drug for Covid-19 among 47 existing drugs allowed for medical use.

The researchers said Olumiant was the optimal choice, given its once-daily oral dosing, high affinity for AAK1 to suppress the viral entry, and acceptable side-effect profile.

They also predicted that the potential for combination therapy with Olumiant was high because the drug had “low plasma protein binding and minimal interaction with CYP enzymes and drug transporters.”

“There is the potential for combining baricitinib (Olumiant) with the direct-acting antivirals (lopinavir or ritonavir and remdesivir) currently being used in the COVID-19 outbreak since it has minimal interaction with the relevant CYP drug-metabolizing enzymes,” the researchers said.

They emphasized that the combined use of Olumiant with antivirals could reduce viral infectivity, viral replication, and the aberrant host inflammatory response.

The AI-based prediction turned out to be arguably accurate. The latest study showed that the use of AI could save time and manpower required for drug development in an urgent infectious disease outbreak, observers said.

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