As the need for a COVID-19 cure continues to strain the health industry, researchers look to re-purpose existing medications in order to reduce the time searching for a cure. Researchers at the Chinese Academy of Sciences, Shenzhen Institutes of Advanced Technology (SIAT) have identified four drugs that could potentially prevent replication of the virus.
The researchers at SIAT used an assortment of artificial intelligent platforms to utilize deep learning and molecular simulation in the screening of 1,906 established drugs. Authors of the study claim that other computational drug screening methods typically depend upon a single technique or lack experimental validation. Haiping Zhang, an author on the study said, “We have demonstrated the value of our novel hybrid approach that combines deep learning technologies with more traditional simulations of molecular dynamics.”
The screening method focused on each drug's ability to bind with the virus’s RNA-dependent RNA polymerase (RdRP). The hybrid screening method included DFCNN, DeepBindBC, Autodock Vina, pocket localized molecular dynamics simulation, metadynamics, and SIAT’s in-house developed tools. The tested drugs came from the TargetMol-Approved Drug Library, and some had different results within DFCNN, DeepBindBC, and Autodock Vina. Some of the varied results include amenamevir and azithromycin scoring higher on Autodock Vina, and odanacatib and nitisinone scoring higher on DFCNN.
The screening was able to identify four drugs that had the potential to prevent replication of the virus. The two drugs pralatrexate, a chemotherapy for lymphoma, and azithromycin, an antibiotic, were found to be capable of preventing the replication. After more experimentation, pralatrexate looked to be potentially more effective than Gilead Sciences’ remdesivir, the only approved drug for treating COVID-19.
Pralatrexate was originally approved by the FDA in 2009 for the treatment of terminal illnesses. The drug was able to bind to the novel virus SARS-CoV-2’s RdRP, enabling it to copy the genomic information that allows the infected cells to survive, and stopped the RNA synthesis.
Due to pralatrexate’s potency, it may have limited use in treating COVID-19 patients. The drug presents many serious side effects such as low blood cell counts, mucositis, severe skin reactions, tumor lysis syndrome, increased risk of serious reactions in kidney patients, fever, dehydration, nausea, and is a risk for pregnant and nursing women. Nevertheless, researchers will continue to search for other possible treatment options for COVID-19, with a focus on repurposing existing medications that could benefit current coronavirus patients.
