During a public health emergency, repurposing existing drugs is seen as a fast path to potential cures, so several companies and academic groups have spent much of the past year looking for COVID-19 remedies in marketed medicines. Now a research team from China has identified an approved chemotherapy drug as a possible coronavirus treatment.
Using a combination of computational screening tools, scientists at the Shenzhen Institutes of Advanced Technology (SIAT) of the Chinese Academy of Sciences showed that Folotyn (pralatrexate) from Acrotech Biopharma, a chemotherapy originally developed to treat lymphoma, has a powerful could be a 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 as Veklury, has been approved by the FDA for admitted COVID-19 patients.
Artificial intelligence is widely used in drug research, and the SIAT team thought a hybrid approach using deep learning and molecular simulation might be a better solution than a single method approach.
The team used different AI platforms to screen a library of 1,906 currently marketed drugs for their ability to bind to the coronavirus’s RNA-dependent RNA polymerase (RdRP). For RNA viruses such as SARS-CoV-2, RdRp is essential for copying the genomic information that allows them to infect and survive cells. Gilead has shown that remdesivir binds to RdRp and interferes with coronavirus RNA synthesis.
The computational model linked four candidates: pralatrexate, antibiotics amoxicillin and azithromycin, and Gilead’s hepatitis C drug Sovaldi (sofosbuvir).
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Two of the drugs – pralatrexate and azithromycin – inhibited the replication of SARS-CoV-2 in cells. The SIAT researchers admitted that the chemotherapy is linked to several side effects and that its use is limited to an aggressive form of non-Hodgkin lymphoma called peripheral T cell lymphoma. Therefore, the drug may have limited clinical use for COVID-19 patients.
Nevertheless, the study supports the use of a hybrid virtual screening to “aid in drug reuse and facilitate virtual drug screening against other targets in SARS-CoV-2,” the scientists wrote in the study.
Many artificial intelligence based drug screening methods have been applied in COVID-19 drug repurposing research. Previous efforts have also pointed to azithromycin as a possible COVID treatment. And a team at the Cleveland Clinic used AI to analyze nearly 27,000 individuals in the COVID-19 registry and found that those taking popular sleep aids melatonin were less likely to test positive for the new coronavirus.
A successful example emerging from AI-based research is BenevolentAI’s identification of Eli Lilly’s rheumatoid arthritis drug Olumiant as a potential therapy for COVID-19. The JAK inhibitor has won the FDA emergency license as an adjunct to remdesivir for hospital COVID patients who require oxygen support after demonstrating that the combination can shorten recovery time.
The SIAT team is now working to develop additional computational methods that it hopes will generate new drugs to treat COVID-19, it said in a statement.