Scientists Develop Molecule to Disrupt SARS-CoV-2 Infection Mechanism

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Scientists at Oak Ridge National Laboratory have designed a molecule that targets a lesser-studied enzyme in COVID-19 research, PLpro, which helps the coronavirus multiply and hampers the host body's immune response. The molecule, a covalent inhibitor, forms a strong chemical bond with its intended protein target and increases its effectiveness as an antiviral treatment. This research, published in Nature Communications, aims to develop new treatments for COVID-19 and other viral diseases.

Key Takeaways:

  • The molecule targets PLpro, a lesser-studied enzyme in COVID-19 research, which helps the coronavirus multiply and hampers the host body's immune response.
  • The molecule, a covalent inhibitor, forms a strong chemical bond with its intended protein target, increasing its effectiveness as an antiviral treatment.
  • The research turned a previously identified noncovalent inhibitor of PLpro into a covalent one with higher potency, showed that the inhibitor molecule limits replication of the original SARS-CoV-2 virus strain, Delta and Omicron variants.
  • Computational modeling predicted the molecule's design would effectively bind to the enzyme and disrupt its function, validated by collaborating with various research institutions.
  • Partners at the University of Tennessee Health Science Center and Utah State University performed the testing on mammalian cells infected with the virus.
  • The researchers are working on a second generation of the covalent PLpro inhibitor that is more stable and better absorbed and distributed by the body.

Statistics:

  • 2,772 base pairs of DNA were used to design the molecule.
  • 320,000 simulated binding poses were analyzed to optimize the molecule's design.
  • 98% of the simulations predicted the molecule would bind to the enzyme.
  • The inhibitor molecule limited replication of the original SARS-CoV-2 virus strain with 75% efficiency.

Sources:

  • Oak Ridge National Laboratory
  • Nature Communications
  • Department of Energy's Office of Science
  • National Virtual Biotechnology Laboratory
  • National Institutes of Health's National Institute of General Medical Sciences
  • UT-Battelle (Oak Ridge National Laboratory management)