The Advanced Photon Source
a U.S. Department of Energy Office of Science User Facility

APS and IMCA-CAT Help Pfizer Create COVID-19 Antiviral Treatment

The original Argonne press release can be read here.

Pharmaceutical company Pfizer has announced the results of clinical trials of its new oral antiviral treatment against COVID-19. The new drug candidate, Paxlovid, proved to be effective against the SARS-CoV-2 virus, which causes COVID-19, according to results released by Pfizer on Nov. 5.

Scientists at Pfizer created Paxlovid with the help of the ultrabright x-rays of the Advanced Photon Source (APS), a U.S. Department of Energy (DOE) Office of Science user facility at DOE’s Argonne National Laboratory. The research employed data obtained at the  Industrial Macromolecular Crystallography Association Collaborative Access Team (IMCA-CAT) beamline at the APS.

“Today’s news is a real game-changer in the global efforts to halt the devastation of this pandemic,” said Albert Bourla, chairman and chief executive officer of Pfizer, in a company press release. ​“These data suggest that our oral antiviral candidate, if approved or authorized by regulatory authorities, has the potential to save patients’ lives, reduce the severity of COVID-19 infections and eliminate up to nine out of 10 hospitalizations.”

DOE invests in user facilities such as the APS for the benefit of the nation’s scientific community, and supports biological research as part of its energy mission. This research has been critical in the fight against COVID-19. The DOE national laboratories formed the National Virtual Biotechnology Laboratory (NVBL) consortium in 2020 to combat COVID-19 using capabilities developed for their DOE mission, and that consortium helps support research into antiviral treatments such as Paxlovid.

Work to determine the structure of the antiviral candidate was done at the IMCA-CAT beamline at the APS, operated by the Hauptman-Woodward Medical Research Institute (HWI) on behalf of a collaboration of pharmaceutical companies, of which Pfizer is a member.

As a member of IMCA-CAT, Pfizer routinely conducts drug development experiments at the APS, and the process of narrowing down and zeroing in on this drug candidate was performed over many months, according to Lisa Keefe, executive director of IMCA-CAT and vice president for advancing therapeutics and principal scientist at Hauptman-Woodward Medical Research Institute. IMCA-CAT, she said, delivers quality results in a timely manner, much faster than the home laboratories of the companies themselves can do.

Access like this to a DOE facility such as the APS, she said, is vitally important for a breakthrough like Paxlovid to happen.

“This is an important illustration of how valuable the national laboratories are to advancing the work of U.S. industries, and that has a hugely beneficial impact on society,” Keefe said. ​“When the results have a global impact, as in the case of treatments against COVID-19, they motivate us and inspire us.”

IMCA-CAT uses the X-rays of the APS to probe the atomic structures of proteins, like those that make up the SARS-CoV-2 virus. Scientists use this information to see how potential drug compounds may interact with the virus. This lays the groundwork for the creation of new vaccines and potentially effective treatments, such as Paxlovid.

If approved, Paxlovid would be the first oral antiviral specifically designed to inhibit a key protease (3CL) of the SARS-CoV-2 virus. For the latest phase of clinical trials, Pfizer tested the treatment on more than 1200 adults, all of whom had been diagnosed with COVID-19 no more than five days prior, and had at least one medical condition or characteristic that enhanced the risk of severe illness.

Results reported by Pfizer showed an 89 percent reduction in risk of COVID-19-related hospitalization or death, compared with a similar number of patients who took a placebo.

Results of the first phase of trials were recently published in Science.

Pfizer’s next step is to pursue an emergency use authorization from the U.S. Food and Drug Administration.

“This is excellent news, and we’re very pleased to have played a part in the creation of this potentially life-saving antiviral treatment candidate,” said Stephen Streiffer, Argonne’s deputy laboratory director for science and technology and director of the APS. ​“DOE facilities such as the APS have performed an important role in the fight against this global pandemic, from providing the foundation for vaccines to enabling more reliable data about the spread of the virus.”

The New York Times: "Pfizer Says Its Antiviral Pill Is Highly Effective in Treating Covid"

The complete text of a Physics Today article by David Kramer can be read here.

This research used resources at the Industrial Macromolecular Crystallography Association Collaborative Access Team (IMCA-CAT) beamline 17-ID, supported by the companies of the Industrial Macromolecular Crystallography Association through a contract with Hauptman-Woodward Medical Research Institute. This research used resources of the Advanced Photon Source, a U.S. DOE Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357.Additional funding for beamlines used for COVID-19 research at the APS is provided by the National Institutes of Health (NIH) and by DOE Office of Science Biological and Environmental Research. Supplemental support for COVID-19 research was provided by the DOE Office of Science through the National Virtual Biotechnology Laboratory, a consortium of DOE national laboratories focused on response to COVID-19 with funding provided by the Coronavirus CARES Act.

The U. S. Department of Energy Office of Science’s Advanced Photon Source (APS) at Argonne National Laboratory is one of the world’s most productive X-ray light source facilities. The APS provides high-brightness X-ray beams to a diverse community of researchers in materials science, chemistry, condensed matter physics, the life and environmental sciences, and applied research. These X-rays are ideally suited for explorations of materials and biological structures; elemental distribution; chemical, magnetic, electronic states; and a wide range of technologically important engineering systems from batteries to fuel injector sprays, all of which are the foundations of our nation’s economic, technological, and physical well-being. Each year, more than 5,000 researchers use the APS to produce over 2,000 publications detailing impactful discoveries, and solve more vital biological protein structures than users of any other X-ray light source research facility. APS scientists and engineers innovate technology that is at the heart of advancing accelerator and light-source operations. This includes the insertion devices that produce extreme-brightness X-rays prized by researchers, lenses that focus the X-rays down to a few nanometers, instrumentation that maximizes the way the X-rays interact with samples being studied, and software that gathers and manages the massive quantity of data resulting from discovery research at the APS.

Argonne National Laboratory seeks solutions to pressing national problems in science and technology. The nation’s first national laboratory, Argonne conducts leading-edge basic and applied scientific research in virtually every scientific discipline. Argonne researchers work closely with researchers from hundreds of companies, universities, and federal, state and municipal agencies to help them solve their specific problems, advance America’s scientific leadership and prepare the nation for a better future. With employees from more than 60 nations, Argonne is managed by UChicago Argonne, LLC for the U.S. Department of Energy’s Office of Science.

The U.S. Department of Energy’s Office of Science is the single largest supporter of basic research in the physical sciences in the United States and is working to address some of the most pressing challenges of our time. For more information, visit https://​ener​gy​.gov/​s​c​ience.

 

 

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