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

During a public health emergency, repurposing existing medicines is considered to be a fast route to potential cures, so several companies and academic groups have spent much of the last year looking for COVID-19 remedies in already marketed drugs. Now, a research team from China has identified an approved chemotherapy drug as a potential coronavirus treatment.

By using a combination of computational screening tools, scientists at the Chinese Academy of Sciences’ Shenzhen Institutes of Advanced Technology (SIAT) showed that Acrotech Biopharma’s Folotyn (pralatrexate), a chemotherapy originally developed to treat lymphoma, could be a potent remedy against SARS-CoV-2, the novel coronavirus behind COVID-19.

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

Artificial intelligence is widely used in drug research, and the SIAT team figured a hybrid approach utilizing deep learning and molecular simulation could be a better solution than one based on a single method.

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 like SARS-CoV-2, RdRp is essential for copying the genomic information that allows them to infect cells and survive. Gilead has shown remdesivir binds to RdRp and interferes with the coronavirus's RNA synthesis.

The computational model pegged 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 conceded that the chemotherapy is linked to several side effects and its use is limited to an aggressive form of non-Hodgkin’s 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 “help with drug repurposing application 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 potential COVID treatment. And a team at the Cleveland Clinic used AI to analyze nearly 27,000 individuals in its COVID-19 registry and found those taking popular sleep aid melatonin were less likely to test positive for the novel coronavirus.

One successful example coming out of 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 won FDA emergency authorization as an add-on to remdesivir for hospitalized COVID patients who need oxygen support after showing the combo could cut recovery time.

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