In early 2020, when the novel coronavirus was gaining momentum but had not yet been named a pandemic, computational chemist Marti Head of Oak Ridge National Laboratory – along with scientists and researchers around the globe – abruptly switched her focus to the fight against COVID-19.

The world was struggling to understand this new virus known as severe acute respiratory syndrome coronavirus 2, or SARS-CoV-2. But Head and others already knew that defeating such a highly transmissible pathogen was going to require a multi-pronged approach, including vaccines and multiple drug therapies.

After viable COVID-19 vaccines became available for emergency use by the U.S. Food and Drug Administration – a feat achieved in record time – mainstream talk of therapeutics dropped off.

Yet, effective drug treatments still needed to be in the mix.

“There’s been so much focus on vaccines that development of antibodies and antiviral drugs kind of get overlooked,” she had said in February 2021. “We absolutely, positively need vaccines … (to) help give us that kind of herd immunity to protect the widest population that we can. But we also need other tools.”

Development of drug treatments is complex, and it often takes years, even decades, to move from scientific discovery all the way through the process to an approved, publicly available therapeutic. As the spread of COVID was ramping up in 2020, the Department of Energy launched the National Virtual Biotechnology Laboratory, or NVBL, program with funding from the U.S. government’s CARES Act and began shoring up teams from across DOE’s national laboratory system.

The tasks at hand required two things: creativity and speed. And the DOE labs are delivering.

Molecular Design for Medical Therapeutics is one of the NVBL program’s teams. Led by Head, the group leverages deep knowledge and expert skills in artificial intelligence and computational screening techniques used for early stage biomedical research. In the past, team scientists have, among other projects, studied targets for more effective antibiotics and treatments for cancer.

Data gleaned from the molecular design team’s more recent efforts, shared with the pharmaceutical research community, could help shorten the drug development timeline on the COVID front. The team also includes materials characterization at x-ray, light and neutron sources and nanoscience research to accelerate scientific discovery for therapeutics targeting SARS-CoV-2.

As many national lab scientists turned their talent, tools and attention from saving energy to saving lives, they gained a new level of expertise, resulting in the development of innovative research processes likely to have longer term impacts as they shift back to their energy-funded missions.

Energy mission, drug discovery

Head joined ORNL in February 2018 from GlaxoSmithKline initially to lead the lab’s Joint Institute for Biological Sciences, a collaboration with the University of Tennessee. She spent about two years developing strategies to fund biological research that would leverage the lab’s powerful and innovative DOE-funded user facilities, such as the Oak Ridge Leadership Computing Facility, Spallation Neutron Source and High Flux Isotope Reactor, and the Center for Nanophase Materials Sciences, and managing ORNL’s participation in the multi-national lab consortium called Accelerating Therapeutics for Opportunities in Medicine, or ATOM.

When the nation sounded the alarm on COVID-19, she drew upon her decades of pharmaceutical research and drug development experience in computer-aided drug discovery to help DOE pull together a dream team of molecular biophysicists, computational biologists, chemists and others.

An ORNL-led team comprising researchers from multiple DOE national laboratories is using artificial intelligence and computational screening techniques – in combination with experimental validation – to identify and design five promising drug therapy approaches to target the SARS-CoV-2 virus. Credit: Michelle Lehman/ORNL, U.S. Dept. of Energy

Promising approaches

The DOE NVBL molecular design team surveyed the larger biomedical research landscape. ORNL along with DOE national labs Sandia, Lawrence Livermore, SLAC National Accelerator Laboratory, Lawrence Berkeley, Pacific Northwest, Argonne and Brookhaven are using artificial intelligence and computational screening techniques – in combination with experimental validation – to identify and design drug therapies to target the SARS-CoV-2 virus.

“(DOE) at that time … really wanted to focus on computation,” Head said. Computation – especially when it involves ORNL’s Summit, the nation’s most powerful supercomputer – afforded the molecular design team an incredible jumpstart in tackling an enormous coronavirus challenge. Other ORNL-led teams were quickly revealing the potential of existing antiviral drug compounds and characterizing the impact the virus was having on human cells, managing massive amounts of data in a matter of hours.

Still other ORNL scientists were further discovering the nature of the novel coronavirus using crystallography experiments with x-rays and neutrons.

Source: ORNL