Could a lymphoma drug work better against COVID-19 than Gilead’s remdesivir?

During a public health emergency, reuse of existing drugs is seen as a fast track to potential cures, so several companies and academic groups have spent much of the last year researching cures for COVID. -19 in drugs already on the market. Now, a Chinese research team has identified a chemotherapy drug approved as a potential treatment for the coronavirus.

Using a combination of computer screening tools, scientists from the Shenzhen Institutes of Advanced Technology (SIAT) of the Chinese Academy of Sciences have shown that Acrotech Biopharma’s Folotyn (pralatrexate), a chemotherapy initially developed to treat lymphoma, could be a potent cure for SARS- CoV-2, the new coronavirus behind COVID-19.

They found that pralatrexate inhibited SARS-CoV-2 replication more strongly than Gilead Sciences’ remdesivir under the same experimental conditions, according to results published in the journal PLOS Computational Biology. Remdesivir, sold under the name Veklury, is approved by the FDA for hospital patients with COVID-19.

Artificial intelligence is widely used in drug research, and the SIAT team felt that a hybrid approach using deep learning and molecular simulation might be a better solution than a single method based method. .

The team used different AI platforms to screen a library of 1906 drugs currently on the market for their ability to bind to the coronavirus RNA-dependent RNA polymerase (RdRP). For RNA viruses like SARS-CoV-2, RdRp is essential for copying the genomic information that allows them to infect cells and survive. Gilead has shown that remdesivir binds to RdRp and interferes with the synthesis of coronavirus RNA.

The computational model indexed four candidates: pralatrexate, the antibiotics amoxicillin and azithromycin, and the drug Sovaldi (sofosbuvir) against Gilead’s hepatitis C.

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Two of the drugs – pralatrexate and azithromycin – inhibited the replication of SARS-CoV-2 in cells. SIAT researchers have admitted that chemotherapy is linked to several side effects and that its use is limited to an aggressive form of non-Hodgkin lymphoma called peripheral T lymphoma. Therefore, the drug may have limited clinical use in patients with COVID-19.

Nonetheless, the study supports the use of hybrid virtual screening to “aid drug reuse and facilitate virtual drug screening against other targets of SARS-CoV-2,” the scientists wrote in the report. study.

Numerous artificial intelligence-based drug testing methods have been applied in COVID-19 drug reuse research. Previous efforts have also indicated azithromycin as a potential treatment for COVID. And a team from the Cleveland Clinic used AI to analyze nearly 27,000 people in its COVID-19 registry and found that those who took the popular sleep aid melatonin were less likely to test positive for the novel coronavirus. .

A successful example from AI-based research is BenevolentAI’s identification of Eli Lilly’s rheumatoid arthritis drug Olumiant as a potential treatment for COVID-19. The JAK inhibitor has obtained emergency clearance from the FDA as an adjunct to remdesivir for COVID hospital patients who require oxygen supply after showing the combo can reduce recovery time.

The SIAT team is currently working on developing additional computational methods that it hopes will generate new drugs to treat COVID-19, he said in a statement.