COVID-19 Initiative in 2020 Catalyzed Impactful Research
Detail from molecular representation of Delta SARS-CoV-2 all-atom model by Lorenzo Casalino and Abigail Dommer, Amaro Lab, University of California, San Diego.
RCSA’s quick support of COVID-19 research at the start of the pandemic in 2020 helped catalyze several projects with remarkable results.
The COVID-19 Initiative was launched in April 2020 with a series of online meetings attended by about 120 members of the RCSA community – Cottrell Scholars, Scialog Fellows, and Scialog Facilitators with expertise in chemistry, physics, optics, computer and data science, biomedicine, and engineering. The event was run like a virtual Scialog initiative, with one exception: RCSA’s usual early-career limitation for proposal writers was relaxed,
“We felt it was important to encourage the wide range of scientists in our network to contribute their expertise and methods during this pandemic,” said RCSA President & CEO Daniel Linzer. “Their work could help fight this virus, or the next one.”
Just four weeks after the meeting, 13 individual investigators (making up seven teams) received awards of $55,000. Here are highlights from a few of the projects:
The project Pan-Covid-19 MultiValent Binders (MVBs) to Block Virus Entry was a collaboration between Scialog: Chemical Machinery of the Cell Facilitator Rommie Amaro, Chemistry and Biochemistry, University of California, San Diego, CMC Fellow Ronit Freeman, Biomaterials, University of North Carolina at Chapel Hill, and Cottrell Scholar 2001 Carlos Simmerling, Chemistry, Stony Brook University.
"My group had previously worked with influenza virus, but not any of the coronaviruses,” said Amaro. “The early, flexible support from RCSA was essential to the success of this work and our ability to quickly move into this new direction. Our work to develop a cell-surface-based COVID-19 diagnostic was only possible through this new collaboration.”
Modeling work by Amaro and Simmerling, which led to a deeper understanding of the dynamics of the spike protein and how it interacts with cell surface receptors, was reported in The New York Times. A second part of their work, which helped explain how virus particles maintain their integrity in exhaled droplets, was also featured in the Times.
Simmerling said that without support from the initiative, his lab would not have been able to work on this project for more than a few weeks. “The RCSA funding allowed us to apply our tools to COVID-19 research and let us spend the time needed to really dive deep into the spike behavior and analyze the long simulations.”
Alongside the modeling work, Freeman’s group was working on new ways to detect the virus. During the pandemic, they developed, patented, and quickly brought to mass-market production a glycopolymer-based lateral flow assay for detecting SARS-CoV-2 and its rapidly emerging variants.
Freeman said that although the team had never met in person, two years of weekly virtual meetings have helped them "grow our joint community and bring our individual networks together, enabling new collaborations and sparking new ideas.” She said their new connections are now making it possible for them to apply for additional funding.
The project Establishing Swift, Sensitive, and Selective (3S) Sensing Technologies – Going Beyond RT-PCR brought together the complementary skills of Freeman and Cottrell Scholar 2013 Zachary Schultz, Chemistry and Biochemistry, The Ohio State University.
“The combination of respective expertise is what made this project possible,” said Schultz. “Ronit’s lab’s experience with protein synthesis and biomolecular engineering enabled my lab to leverage previous experience with SERS of proteins to pivot to virus detection and assess new capture molecules.”
The pair published a paper in ACS Sensors providing a new route to address SARS-CoV-2 and potentially future virus outbreaks. They are now in discussion with companies to license the technology they have patented.
With the project Electric Field-Driven Antigen Enrichment to Achieve Detection of SARS-CoV-2 Nucleocapsid Protein in Urine at the Point-of-Need, Cottrell Scholar 2019 Robbyn Anand, Chemistry, Iowa State University, was able to translate her lab’s work developing a method that integrates a lateral flow assay with electrokinetic enrichment of antigens to the detection of SARS-CoV-2. Her preliminary results catalyzed further funding from the Roy J. Carver Charitable Trust, allowing her lab to improve the electrokinetically enhanced paper-based assay and develop a microfluidic assay for viral RNA based on the same principles. Anand has received a provisional patent on the method and is currently exploring methods to scale-up testing capacity.
The project Targeting the SARS-CoV-2 Frameshift Site Pseudoknot enabled the labs of two 2017 Cottrell Scholars, Amanda Hargrove, Chemistry, Duke University, and CS Katie Mouzakis, Chemistry, Loyola Marymount University, to take on new research directions. The collaboration, which included Victoria D’Souza, Harvard University, and Gary Brewer, Rutgers Robert Wood Johnson Medical School, has identified promising lead molecules that directly bind the SARS-CoV-2 target RNA and inhibit its function.
The funding helped the Mouzakis lab extend their research on regulatory RNAs from a single family of viruses (retroviruses) to include coronaviruses, and to establish their first small molecule targeting project. It extended the Hargrove Lab’s research toward new targets in both pseudoknots and frameshifting elements while allowing for direct comparison of small molecule performance in binding, in vitro, and cell-based assays.
In addition, in an effort to remotely engage undergraduate students in research, Mouzakis integrated the SARS-CoV-2 collaborative project into two of her biochemistry laboratory courses. This work was included in a peer-reviewed pedagogical publication in the Biophysicist in 2021.
“The integration of research into teaching advanced the research while simultaneously supporting the training of a large number of undergraduate students,” Mouzakis said.
RCSA Senior Program Director Andrew Feig, who headed the initiative, said the effort demonstrated the power of philanthropy to move quickly to help address a global crisis.
“We’re proud of the efforts our community of scientists made to contribute their talents toward a better understanding of coronaviruses and their detection,” he said.
