Daily Management Review

Facing Covid-19: the US medical machine


Despite best efforts to reduce case numbers, at state and federal level, COVID-19 has contributed directly to more than 200,000 deaths and wreaked havoc on the economy. The public and the scientific community are eager to know more about what is being done to win the war. One crucial asset in this fight is the Department of Energy (DoE), which has contributed to a huge number of scientific breakthroughs in this area.

Early in the crisis, border restrictions were put in place to reduce the flow of potentially infected internationals coming into the U.S. A number of bills were passed by Congress freeing up trillions of dollars to fund the nationwide health response and to loan money to businesses and self-employed workers struggling due to the economic fallout of the virus. Instructed to take their own initiative, state governors imposed health measures, including stay-at-home orders based on the severity of their local outbreaks, while the president established the White House Coronavirus Task Force, headed by Vice President Mike Pence.

Despite these efforts there is still worry about the possibility of subsequent waves of infection, and with flu season just around the corner and the president and the first lady recently becoming infected, optimism is yet to materialize.

While the U.S. has 4 percent of the world’s population it has around 20 percent of global deaths attributed to Covid-19. Worryingly, the unemployment rate, 7.9 percent [1] or 12.6 million people, although falling — continues to highlight an extremely disrupted economy.

"The big concern this year, of course, is that we are going to see what could be a perfect storm of accelerated COVID-19 activity as people gather more inside […] as they become continually fatigued with the mask wearing, […] and as they are exposed to seasonal influenza," said [2] Dr. Jeanne Marrazzo, director of the division of infectious diseases at the University of Alabama at Birmingham, during an Infectious Disease Society of America briefing in September.

Weapons at the disposal of the Department of Energy
Since the days of the Manhattan Project, the DoE’s National Lab complex [3] has been at the forefront of scientific development, in quests ranging climate change research to the origins of the universe. Now faced with Covid-19, tens of thousands of scientists and specialist staff from this institution have come together with other government agencies, and researchers from universities and the private sector, to find the weapons needed to defeat the virus.
The DoE’s Office of Science’s Biological and Environmental Research [4] program played a pivotal role in Covid-19 research, bringing together interdisciplinary teams from across the sciences. It was crucial in the development of the DoE’s National Virtual Biotechnology Laboratory  [5] (NVBL), a consortium of all 17 DoE national laboratories. Among other features, the consortium leverages expertise in protein structure discovery, along with supercomputing  [6] — which is used to simulate potential drug-target interactions and greatly enhance modern pharmaceutical capabilities — in order to combat the virus.
The NVBL focuses on a number of key areas. At its disposal the DoE has X-ray [7]  and neutron sources [8] at multiple facilities capable of providing protein structure data vital for computational modelling and drug and vaccine experimentation and development. These capabilities help the nation’s scientist to acquire a clear picture of the virus they are combatting.
The next area is the computation itself. The DoE possesses a number of facilities with supercomputing capabilities [9], which through a collaborative effort have developed a virtual library of every known chemical, some 5 billion — this is then used in molecular modeling of drug interactions with Covid-19 with the assistance of artificial intelligence and machine learning.
NVBL also has expertise in genomic sequencing, epidemiological and logistics support, clinical and non-clinical testing, as well as extensive manufacturing capabilities and multi-tier specialized cloud architecture for Covid-19 health data.

Progress being made against the virus
Using these unparalleled capabilities, DoE scientists at Argonne National Lab were able to develop biochemical assays to assess the activity of a specific protein of SARS-CoV-2, the virus that causes Covid-19. They then correctly predicted that an FDA-approved drug, Tipiracil [10], would inhibit the activity of the protein. Tipiracil had limited antiviral activity, however, researchers have hopes that its efficacy can be augmented so that more powerful Covid-19 therapies can be developed.
Following similar logic, another study [11] from the University of Chicago took around 1900 drugs either approved for human use by FDA or in late stage clinical development and screened them against a virus related to Covid-19. After testing the top 30 candidates for anti-SARS-CoV-2 activity, 20 drugs were recognized as having antiviral activity. Not only were half of these not previously identified as having this effect, one drug, masitinib [12], was found to completely block the protease 3CLpro, an enzyme crucial for SARS-CoV-2 infection and replication.
“Our colleagues at Argonne solved the structure of masitinib bound to the active site of 3CLpro. You can think of it as a key that perfectly fits in a lock, inactivating the protein and preventing infection,” said [13] Dr. Glenn Randall, speaking before the Subcommittee on Energy to the House of Representatives.
The University of Chicago aims to study this effect further, and the drug manufacturer, AB Science, has a separate study in progress [14]. It was also noted that as masitinib has shown activity against multiple coronaviruses there is potential for stockpiling the drug for future pandemics.
Other results coming out of DoE research have involved targeting a different component of SARS-CoV-2, protease PLpro. Through a collaboration [15] between Argonne and the University of Chicago, scientists confirmed activity against PLpro and — for some of the compounds — showed activity blocking replication of the virus.
These are just a few of the significant contributions made by the DoE in the war on Covid-19. While effective vaccines are not likely to be available until next year, new therapeutics are being spearheaded all the time. Most recently, the president himself was allegedly treated with experimental antibody infusion, demonstrating that advances are constantly being made.