In laboratory experiments, pralatrexate exceeds remdesivir against SARS-CoV-2 – ScienceDaily

A new computerized drug screening strategy, combined with laboratory experiments, suggests that pralatrexate, a chemotherapy drug originally developed to treat lymphoma, could be reused to treat Covid-19. Haiping Zhang of Shenzhen Institutes of Advanced Technology in Shenzhen, China and colleagues present these findings in the open access journal PLOS Computational Biology.

Given that the Covid-19 pandemic causes disease and death worldwide, better treatments are urgently needed. A shortcut could be the reuse of existing drugs that were originally developed to treat other conditions. Computational methods can help identify these drugs by simulating how different drugs would interact with SARS-CoV-2, the virus that causes Covid-19.

To help virtual screening of existing drugs, Zhang and colleagues combined several computational techniques that simulate drug-virus interactions from different, complementary perspectives. They used this hybrid approach to examine 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 new screening approach identified four promising drugs, which were then tested against SARS-CoV-2 in laboratory experiments. Two of the drugs, pralatrexate and azithromycin, successfully inhibited the replication of the virus. Other laboratory experiments have shown that pralatrexate inhibits viral replication more strongly than remdesivir, a drug currently used to treat patients with Covid-19.

These findings suggest that pralatrexate may be reconstituted for the treatment of Covid-19. However, this drug for chemotherapy can cause significant side effects and is used for people with terminal lymphoma, so immediate use for patients with Covid-19 is not guaranteed. However, the findings support the use of the new screening strategy to identify drugs that could be reused.

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

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