During a public health emergency, the recovery of existing medicines is considered to be a fast track to potential remedies, so several companies and academic groups have spent much of the last year looking for COVID-19 remedies in already marketed medicines. Now, a research team in China has identified a drug approved for chemotherapy as a potential coronavirus treatment.
Using a combination of computational screening tools, scientists at the Shenzhen Institute of Advanced Technology of the Chinese Academy of Sciences (SIAT) have shown that Acrototech Biopharma’s Folotin (pralatrexate), a chemotherapy originally developed to treat lymphoma, could be a powerful remedy against SARS-CoV-2, the novel coronavirus behind COVID-19.
They found that pralatrexate more strongly inhibits SARS-CoV-2 replication than remdesivir Gilead Sciences under the same experimental conditions, according to results published in the journal PLOS Computational Biology. Remdesivir, sold as Veklury, is FDA approved for patients hospitalized with COVID-19.
Artificial intelligence is widely used in drug research, and the SIAT team believed that a hybrid approach using deep learning and molecular simulation could be a better solution than one based on a single method.
The team used various AI platforms to examine a library of 1,906 drugs currently marketed for their ability to bind to RNA coronavirus-dependent RNA polymerase (RdRP). For RNA viruses such as SARS-CoV-2, RdRp is essential for copying genomic information that allows them to infect cells and survive. Gilead has shown that remdesivir binds to RdRp and interferes with coronavirus RNA synthesis.
The calculation model linked four candidates: pralatrexate, the antibiotics amoxicillin and azithromycin and the hepatitis C drug Gilead Sovaldi (sofosbuvir).
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Two of the drugs – pralatrexate and azithromycin – inhibited SARS-CoV-2 replication in cells. SIAT researchers have recognized that chemotherapy is linked to several side effects and its use is limited to an aggressive form of non-Hodgkin’s lymphoma called T-cell peripheral lymphoma. Therefore, the drug may have limited clinical use in patients with COVID-19. .
However, the study supports the use of hybrid virtual screening to “help apply drug reuse and facilitate virtual drug screening against other SARS-CoV-2 targets,” the scientists wrote in the study.
Many methods of detecting drugs based on artificial intelligence have been applied in research on the reconditioning of COVID-19 drugs. Previous efforts have also indicated azithromycin as a potential COVID treatment. And a team at the Cleveland Clinic used AI to analyze nearly 27,000 people on its COVID-19 registry and found that those who took popular melatonin for sleep were less likely to test positive for the new coronavirus.
A successful example resulting from AI-based research is the identification of BenevolentAI with the drug Olumiant for Eli Lilly’s rheumatoid arthritis as a potential therapy for COVID-19. The JAK inhibitor won FDA emergency authorization as a remdesivir supplement for patients hospitalized with COVID who need oxygen support after showing that the combination could reduce recovery time.
The SIAT team is now working to develop additional computational methods that it hopes will generate new drugs to treat COVID-19, a statement said.