t typically takes many years of experiments to develop a new medicine. Although vaccines to protect against disease from the novel coronavirus are starting to reach clinics around the world, patients and doctors will still need treatments to manage COVID-19 symptoms for some time.

At Pacific Northwest National Laboratory (PNNL), computational biologists, structural biologists, and analytical chemists are using their expertise to safely accelerate the design step of the COVID-19 drug discovery process.

Rather than finding a new drug by trial and error, scientists are taking the three-dimensional structures of proteins from the novel coronavirus and using computer modeling and machine learning to identify a unique molecule that best fits inside a binding pocket on a protein’s surface. Ideally, that molecule clogs the viral protein and prevents it from functioning.

“Drug research and development is a complex, costly, and time-consuming process, particularly considering the majority of molecules advanced from the design phase fail in clinical trials,” said PNNL computational data scientist Neeraj Kumar. “Computer-based screening incorporates chemical information during the design process to increase a drug candidate’s potential for success in clinical testing.”

Developing an approach to speed drug discovery during this pandemic could also reveal new design steps that might be useful during the next outbreak.

Clogging coronavirus proteins

There are almost 30 different proteins in this novel coronavirus that are potential targets for COVID-19 drug discovery. Combine that with millions of molecules that are potential drug candidates, and the possibilities for matching molecules to specific proteins are mind-boggling.

To narrow the options towards molecules with potential to become medicines, Kumar and his team first use molecular docking to virtually screen libraries of known molecules and regulatory-approved drugs. Ones that fit in the binding pocket of a particular coronavirus protein make the short list for the next step of the process: testing the fit with actual proteins and molecules.

Experimental scientists then combine the molecules on this short list with purified coronavirus protein and “weigh them” with native mass spectrometry to see if the protein picked up the molecule. This technique measures interactions between the protein and the molecules and can confirm the predicted binding.

Image Credit:   Timothy Holland | Pacific Northwest National Laboratory

Post by Amanda Scott, NA CEO.  Follow her on twitter @tantriclens

Thanks to Heinz V. Hoenen.  Follow him on twitter: @HeinzVHoenen

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