Colored scanning electron microscope image of an apoptotic cell (pink) that is heavily infected with SARS-COV-2 virus particles (green) and that was isolated from a patient sample. The image was taken at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: National Institute for Allergy and Infectious Diseases / NIH, 2020 (CC0)

A novel computational strategy for drug screening combined with laboratory experimentation suggests that pralatrexate, a chemotherapy agent originally developed to treat lymphoma, could potentially be used to treat Covid-19. Haiping Zhang from the Shenzhen Institutes of Advanced Technology in Shenzhen, China, and colleagues present these results in the open access journal PLOS Computational Biology.

As the Covid-19 pandemic leads to disease and death around the world, better treatments are urgently needed. One shortcut might be to reuse existing drugs originally designed to treat other conditions. Computational methods can help identify such drugs by simulating how different drugs would interact with SARS-CoV-2, the virus that causes Covid-19.

To support the virtual screening of existing drugs, Zhang and colleagues combined several computer techniques that simulate drug-virus interactions from different, complementary perspectives. They used this hybrid approach to screen 1,906 existing drugs for their potential ability to inhibit SARS-CoV-2 replication by targeting a viral protein called RNA-dependent RNA polymerase (RdRP).

The novel screening approach identified four promising drugs that were then tested against SARS-CoV-2 in laboratory experiments. Two of the drugs, pralatrexate and azithromycin, successfully stopped the virus from replicating. Further laboratory experiments showed that pralatrexate inhibited virus replication more than remdesivir, a drug currently used to treat some Covid-19 patients.

These results suggest that pralatrexate could potentially be used to treat Covid-19. However, this chemotherapy drug can cause significant side effects and is used in people with terminal lymphoma, so immediate use in Covid-19 patients is not guaranteed. However, the results support the use of the new screening strategy to identify drugs that could be used for other purposes.

“We demonstrated the value of our novel hybrid approach, which combines deep learning technologies with more traditional simulations of molecular dynamics,” says Zhang. He and his colleagues are currently developing additional calculation methods to generate novel molecular structures that could be developed into new drugs for the treatment of Covid-19.

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More information:
Zhang H., Yang Y., Li J., Wang M., Saravanan KM, Wei J. et al. (2020) A novel virtual screening method identifies pralatrexate as an inhibitor of SARS-CoV-2 RdRp and reduces virus replication in vitro. PLoS Comput Biol 16 (12): e1008489. DOI: 10.1371 / journal.pcbi.1008489 Provided by the Public Library of Science

Quote: New virtual screening strategy identifies existing drug that inhibits the Covid-19 virus (2020, December 31), accessed on December 31, 2020 from https://medicalxpress.com/news/2020-12-virtual-screening -strategy-drug-inhibits.html

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