New virtual screening strategy identifies existing drug that inhibits Covid-19 virus


PICTURE: Colorized scanning electron micrograph of an apoptotic cell (pink) heavily infected with SARS-COV-2 virus particles (green), isolated from a patient sample. Image captured at the NIAID Integrated Research Facility (IRF) … see more

Credit: National Institute of Allergy and Infectious Diseases / NIH, 2020 (CC0)

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

With the Covid-19 pandemic causing illness and death around the world, better treatment is urgently needed. One shortcut could be to reuse existing drugs that were originally developed to treat other conditions. Computer methods can help identify these drugs by simulating how different drugs would interact with SARS-CoV-2, the virus that causes Covid-19.

To facilitate virtual screening for existing drugs, Zhang and his colleagues combined several computational techniques that simulate drug-virus interactions from different and 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 new screening approach identified four promising drugs, which were then tested against SARS-CoV-2 in lab experiments. Two of the drugs, pralatrexate and azithromycin, were successful in inhibiting virus replication. Other laboratory experiments have shown that pralatrexate inhibits viral replication more strongly than remdesivir, a drug currently used to treat some patients with Covid-19.

These results suggest that pralatrexate could potentially be reused to treat Covid-19. However, this chemotherapy drug can cause significant side effects and is used for people with terminal lymphoma, so its immediate use in Covid-19 patients is not guaranteed. Still, the results 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 which combines deep learning technologies with more traditional simulations of molecular dynamics,” says Zhang. He and his colleagues are currently developing additional computational methods to generate new molecular structures that could be developed into new drugs to treat Covid-19.


Peer reviewed; Simulation / modeling

In your cover, please use this URL to provide access to the article available for free in Computational Biology PLOS:
http: // /ploscompbiol /article? id =ten.1371 /newspaper.pcbi.1008489

Quote: Zhang H, Yang Y, Li J, Wang M, Saravanan KM, Wei J, et al. (2020) New Virtual Screening Procedure Identifies Pralatrexate as an Inhibitor of SARS-CoV-2 RdRp and Reduces Viral Replication in Vitro. PLoS Comput Biol 16 (12): e1008489.
https: //do /ten.1371 /newspaper.pcbi.1008489

Funding: This work was in part supported by the National Key Research and Development Program of China under Grants No. 2018YFB0204403 (YW) and 2019YFA0906100 (XW); Strategic Priority CAS Project XDB38000000 to YW, National Large Science and Technology Project under Grant No. 2018ZX10101004 (YY), National Science Foundation of China under Grant No. U1813203 (YW); the National Youth Natural Science Foundation of China (Grant No. 31601028: YP); the Shenzhen Basic Research Fund under Grant no. JCYJ20190807170801656 (JL), JCYJ20180507182818013 (YW), JCYJ20170413093358429 (YW) and the SIAT Innovation Program for Excellent Young Researchers (JL). Funders played no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: No author has competing interests.

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