Scientist at Berkeley Lab Played a Hand in “Inescapable” COVID-19 Antibody Discovery
An antibody therapy that appears to neutralize all known SARS-CoV-2 strains, and other coronaviruses, was developed with a little help from structural biologist Jay Nix
By Aliyah Kovner
Lifesaving COVID-19 vaccines are allowing us to feel optimistic again, after more than a year of anxiety and tragedy. But vaccines are only one side of the coin – we also need treatments that can prevent severe disease after someone has been infected. In the past year, there has been significant progress in developing effective antibody-based therapies, and three drugs are currently available through emergency use authorization (EUA) by the Food and Drug Administration.
Sotrovimab, the newest antibody therapy, was developed by GlaxoSmithKline and Vir Biotechnology after a large collaborative study by scientists from across the nation discovered a natural antibody (in the blood of a COVID-19 survivor) that has remarkable breadth and efficacy.
Experiments showed that this antibody, called S309, neutralizes all known SARS-CoV-2 strains – including newly emerged mutants that can now “escape” from previous antibody therapies – as well as the closely related original SARS-CoV virus.
Jay Nix, leader of the Molecular Biology Consortium based at Berkeley Lab’s Advanced Light Source (ALS), used beamlines at the ALS and beamlines at SLAC’s Stanford Synchrotron Radiation Lightsource to perform X-ray crystallography on samples of survivor-derived antibodies during an early phase of the study. His work, alongside other crystallography and cryo-electron microscopy findings, helped generate detailed structural maps of how these antibodies bind to the SARS-CoV-2 spike protein, allowing the wider team to select the most promising contenders and advance them to cell culture- and animal-based studies. Following exciting lab results, the developers designed sotrovimab based on the structure of S309, and evaluated it in clinical trials.
The FDA granted an EUA for sotrovimab in late May after trials showed that people with mild to moderate COVID-19 infections who received an infusion of the therapy had an 85% reduction in rates of hospitalization or death, compared with placebo.
But the team didn’t stop there.
Understanding that new mutations could arise and that a novel pathogenic coronavirus could emerge from an animal-human crossover event, the scientists began a follow-up study to deeply explore what factors make antibodies resistant to viral escape and how certain antibodies are also broadly reactive against diverse, related viruses. Using biochemical and structural analysis, deep mutational scanning, and binding experiments, they identified one antibody with unparalleled universal potency.
“This antibody, which binds to a previously unknown site on the coronavirus spike protein, appears to neutralize all known sarbecoviruses – the genus of coronaviruses that cause respiratory infections in mammals,” said Nix, who is an affiliate in Berkeley Lab’s Biosciences Area. “And, due to the unique binding site on mutation-resistant part of the virus, it may well be more difficult for a new strain to escape.”
Subsequent tests in hamsters suggest that this antibody could even prevent a COVID-19 infection if given prophylactically. The new work was published in Nature.
The Advanced Light Source and SLAC’s Stanford Synchrotron Radiation Lightsource are Department of Energy Office of Science User Facilities.
Silicon Nanowire Offers Efficient High-Temperature Thermoelectric System
Berkeley Lab and Stanford researchers collaborate to find promising solution for converting waste heat to electricity
By Kyra Epstein
With a $2-million grant from the California Energy Commission (CEC), Berkeley Lab has developed a cost-effective thermoelectric waste-heat recovery system to reduce electricity-related carbon emissions. Industries such as the glass, cement, power, and steel sectors expel a huge amount of high-temperature waste heat. Converting this waste heat cost effectively to electricity can provide a zero-carbon source of energy.
The system is based on silicon nanowires developed at Berkeley Lab several years ago. "Using an abundant and inexpensive material like silicon to develop thermoelectric generators will increase market penetration while helping industries minimize energy losses," said Berkeley Lab scientist Vi Rapp.
The funding comes from CEC’s Electric Program Investment Charge (EPIC) program, which funds clean energy innovation to reduce pollution, foster economic development, and meet the state’s climate goals. Worldwide, approximately 45 quads of energy is rejected as waste heat at high temperatures (greater than 300 degrees Celsius) every year. For comparison, the United States uses about 100 quads of primary energy each year.
More than 10 years ago, Berkeley Lab research was focused on low-temperature conversion of waste heat to electricity – a great technology advancement at the time. Because converting waste heat at high temperatures is cost-effective and competes with other zero-carbon and waste heat conversion technologies, high-temperature thermoelectric conversion has been the next sought-after technology advance.
The CEC funded a Berkeley Lab and Stanford team to find a promising solution, and their findings were recently published in the journal Nature Communications. The team developed a technology that uses wafer-scale arrays of porous silicon nanowires with ultra-thin silicon crystallite that allows for an 18 times greater “figure of merit” (an expression representing performance or efficiency) than other high-temperature or bulk silicon thermoelectric technologies.
“High temperatures degrade materials,” said Ravi Prasher, the project lead and a scientist in Berkeley Lab’s Energy Technologies Area. “So we looked at silicon, which is abundant and stable, as well as cheap and reliable. Since bulk silicon does not have good thermoelectric properties, we use silicon to create nanowires – then the physics changes.”
Prasher said the next steps will be working to scale up the system, producing nanowires to test in actual devices.
New Thermal Wave Diagnostic Technique Advances Battery Performance Testing
Berkeley Lab team combines thermal and electrochemistry expertise to make battery testing cheaper and faster
By Kyra Epstein
With rising interest in backup power, solar power storage, and electric vehicles, the race is on to improve the performance of rechargeable lithium batteries. A Berkeley Lab team has developed an easy, fast, and inexpensive method to measure battery performance.
Led by Ravi Prasher and Sean Lubner of the Energy Technologies Area, the new technique uses thermal waves to measure local lithium concentration as a function of depth inside battery electrodes. Their study was recently published in the journal Joule.
“With our technique, you take a battery, and you put the sensor on top of the battery,” Prasher said. “The sensor sends a signal, and depending on the signal frequency, you can change how deep the wave will penetrate. That way, you control the depth of penetration. It’s much cheaper and faster than other diagnostic procedures, and provides a cheap and faster way to measure battery characteristics.”
This approach is called an “operando” technique, which works while the reaction is happening — demonstrating that thermal wave sensing provides spatial information of lithium concentration comparable to experimental results using synchrotron X-ray diffraction, but without having to use a large synchrotron facility such as the Advanced Light Source.
Measuring battery performance is not an easy task, which makes testing new materials to improve battery performance time-consuming and expensive. When testing materials to improve charging speed, different portions of electrodes have different local states of charge and age at varying rates, so spatially averaged chemical information provided by existing battery diagnostic tools is insufficient for understanding degradation of lithium-ion batteries.
Prasher said that the team is now testing the procedure at the lab scale, and the next step will be testing commercial batteries.
“This work shows the strength of interdisciplinary science,” Lubner said. “The project combines techniques and insight from the thermal and electrochemistry communities in order to achieve a capability that would not have otherwise been possible.”
SARS-CoV-2 RBD antibodies that maximize breadth and resistance to escape