UCSF Awarded $67.5 Million to Develop New Antiviral Therapies

Funding from National Institute of Allergy and Infectious Diseases Aims to Prepare for Viruses with Pandemic Potential

By Laura Kurtzman

Scientists at the UC San Francisco (UCSF) Quantitative Biosciences Institute (QBI) and the QBI Coronavirus Research Group (QCRG) have been awarded an initial $67.5 million from the National Institute of Allergy and Infectious Diseases (NIAID) to support its mission of pandemic preparedness.

The award, the largest in UCSF’s history, establishes one of nine Antiviral Drug Discovery (AViDD) Centers for Pathogens of Pandemic Concern across the country. These will be collaborative, multidisciplinary academic-industry research centers to develop candidate antivirals for COVID-19 and other viruses with pandemic potential.

The model we’ve formed at QCRG has the potential to revolutionize and streamline traditional methods of identifying promising therapies by drawing from expertise within organizations, but most importantly across many organizations, to get the best and brightest minds involved.

Nevan Krogan, PhD

The three-year grant will fund early-stage research to identify and validate new viral targets, with an eye to developing small molecules and biotherapeutics that directly block viral targets for SARS-CoV-2, other coronaviruses and other viral families. The most promising drug candidates will then enter late-stage preclinical development. Two additional years of support are anticipated, dependent on expected appropriations and other factors.

“This award brings together an important collaboration among researchers at UCSF and scientific partners across the globe to help accelerate our response to current and future global health crises,” said UCSF Chancellor Sam Hawgood, MBBS. “It is a tremendous validation of QBI’s leadership in this research to date and of the many outstanding scientists involved in this initiative.”

Collaborating to Address Future Pandemics

Headshot of Nevan Krogan
UCSF molecular and systems biologist Nevan Krogan, PhD. Image by Noah Berger

Led by QBI Director Nevan Krogan, PhD, the QCRG is composed of 43 investigators from 14 institutions in the United States and around the world, including more than two dozen scientists from the UCSF schools of Pharmacy and Medicine, with a rich history of collaboration.

In 2020, as the pandemic spread, Krogan joined forces with scientists from UCSF, Gladstone Institutes, Howard Hughes Medical Institute, Icahn School of Medicine at Mount Sinai, and Institut Pasteur to apply their expertise to help find a treatment. Together, they formed the QCRG and were the first to extensively map the protein-protein interaction landscape of SARS-CoV-2.

Innovative Model for Rapid Therapeutic Development

The QCRG Drug Discovery Platform is an integrated suite of experimental and computational technologies that includes biochemistry, screening, structural biology, proteomics, medicinal chemistry, virology, and integrative modeling. It is focused on finding ways of stopping viruses from hijacking the cell’s protein-making machinery to make copies of itself.

“We are deeply honored to receive this important grant that will allow us to continue and accelerate our pioneering efforts toward identifying direct-acting antivirals for multiple viral targets,” said Krogan, who is also a senior scientist at Gladstone Institutes.

“The model we’ve formed at QCRG has the potential to revolutionize and streamline traditional methods of identifying promising therapies by drawing from expertise within organizations, but most importantly across many organizations, to get the best and brightest minds involved,” he said. “On behalf of all of the researchers and scientists comprising QCRG, we applaud the NIH for their vision of pandemic preparedness and supporting measures to preemptively address future outbreaks.”

Along with evaluating drugs that directly interrupt the viral life cycle, QBI will also target viral enzymes and proteins that are involved in viral modulation of the immune system. QCRG’s AVIDD program will focus on targets against SARS-CoV-2, as well as other viruses in eight viral families. These include paramyxoviruses (which cause measles, mumps and respiratory infections), bunyaviruses (viral hemorrhagic fevers), togaviruses (rubella, equine encephalitis), filoviruses (including Ebola viruses and Marburg virus), picornaviruses (including polio, enteroviruses and other cold-causing viruses), and flaviviruses (including the viruses that cause yellow fever, dengue and Zika).

QBI Coronavirus Research Group

Biochemistry Core

Lead: Robert Stroud, PhD
Co-Investigators: Tanja Kortemme, PhD; James Fraser, PhD

In Vitro Virology Core

Lead: Melanie Ott, MD, PhD
Co-Investigators: Adolfo Garcia-Sastre, PhD; Greg Towers, PhD, University College of London; Clare Jolly, PhD, University College of London; Marco Vignuzzi, PhD, Institut Pasteur; Ana Fernandez-Sesma, PhD; Maria Carla Saleh, PhD, Institut Pasteur; Luis Martinez, University of Texas, San Antonio; Lorena Zuliani-Alvarez, PhD; Jennifer Doudna, PhD

Screening Core

Lead: Michelle Arkin, PhD
Co-Investigators: Brian Shoichet, PhD; Fraser; Jason Gestwicki, PhD

In Vivo Virology Core

Lead: Adolfo Garcia-Sastre
Co-Investigators: Kris White, PhD, Icahn School of Medicine at Mount Sinai; Randy Albrecht, PhD, Icahn School of Medicine at Mount Sinai; Vignuzzi; Saleh; Ott

Medicinal Chemistry Core

Lead: Adam Renslo, PhD
Co-Investigators: Shoichet; Jian Jin, PhD, Icahn School of Medicine at Mount Sinai

Proteomics Core

Lead: Danielle Swaney, PhD
Co-Investigators: Robyn Kaake, PhD; Krogan

Structural Biology Core

Lead: David Agard, PhD
Co-Investigators: Kliment Verba, PhD; Yifan Cheng, PhD; Stroud; Fraser

Administrative Core

Lead: Nevan Krogan, PhD
Co-Investigators: Zuliani-Alvarez, Manon Eckhardt, PhD

Integrative Modeling Core

Lead: Andrej Sali, PhD
Co-Investigators: Ignacia Echeverria Riesco, PhD; Pedro Beltrao, PhD, Eth Zurich Institute of Molecular Systems Biology; Michael Keiser, PhD; Kortemme


About UCSF: The University of California, San Francisco (UCSF) is exclusively focused on the health sciences and is dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. It includes UCSF Health, which comprises three top-ranked hospitals, as well as affiliations throughout the Bay Area. Learn more at www.ucsf.edu, or see our Fact Sheet.

About QBI: The Quantitative Biosciences Institute (QBI) is a University of California organized research unit reporting through the UCSF School of Pharmacy. QBI fosters collaborations across the biomedical and the physical sciences, seeking quantitative methods to address pressing problems in biology and biomedicine. Motivated by problems of human disease, QBI is committed to investigating fundamental biological mechanisms, because ultimately solutions to many diseases have been revealed by unexpected discoveries in the basic sciences. Learn more at qbi.ucsf.edu.

About Gladstone Institutes: To ensure our work does the greatest good, Gladstone Institutes focuses on conditions with profound medical, economic, and social impact—unsolved diseases. Gladstone is an independent, nonprofit life science research organization that uses visionary science and technology to overcome disease. It has an academic affiliation with UC San Francisco. Learn more at gladstone.org.