SAN FRANCISCO, May 18, 2022 (GLOBE NEWSWIRE) — Scientists at the UC San Francisco (UCSF) Quantitative Biosciences Institute (QBI) and the QBI Coronavirus Research Group (QCRG) have been initially awarded $67.5 million from the National Institute of Allergy and Infectious Diseases (NIAID) to support its mission of pandemic preparedness. The award covers a three-year period and establishes one of the country’s first Antiviral Drug Discovery (AViDD) Centers for Pathogens of Pandemic Concern, which are multidisciplinary academic-industry research centers to develop candidate antivirals for COVID-19 and other viruses with pandemic potential . Two additional years of support are anticipated dependent on expected appropriations and other factors. The QCRG team, which includes 43 investigators from 14 institutions in the US and around the world, has a rich history of collaboration and was involved in several seminal studies related to SARS-CoV-2 and COVID-19. The grant will fund early-stage research to identify new, direct-acting antivirals that block proteins essential for viruses to replicate. The most promising drug candidates will then enter late-stage preclinical development.
The QCRG Drug Discovery Platform is an integrated suite of experimental and computational technologies that include 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. 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 ( Coronaviridae, Picornaviridae, Togaviridae, Flaviviridae, Hantaviridae, Arenaviridae, Nairoviridae and Paramyxoviridae).
“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 Nevan Krogan, Ph.D., founder of QCRG. “The model we’ve formed at QCRG has the potential to revolutionize and streamline traditional methods of identifying promising therapies by not only drawing from expertise within organizations but most importantly across many organizations to get the best and brightest minds involved. 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.”
Jennifer Doudna, Ph.D., Nobel Laureate in Chemistry, professor of Molecular and Cell Biology and Chemistry at UC Berkeley, senior investigator at Gladstone, and a member of QCRG, added, “As we’ve all seen from the COVID-19 pandemic, we didn’t have the tools we needed when we needed them to fight this virus and save millions of lives around the world. This is a big challenge, so we need efforts like the QCRG, which builds on individual strengths of researchers and brings each member to the table to contribute expertise and exchange ideas so we can effectively tackle global health issues.”
“The research funded by this grant will be important not only for the current COVID-19 pandemic, but for future pandemics as well,” said Melanie Ott, MD, Ph.D., director of the Gladstone Institute of Virology and leader of the In Vitro Virology Core for the QCRG’s AVDD program. “By targeting other RNA viruses with high potential for widespread transmission and pathogenicity, our work will directly contribute to pandemic preparedness in the US and worldwide.”
“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.”
Background on QCRG In 2020 with COVID-19 spreading rapidly around the world, UCSF’s QBI director and senior investigator at Gladstone, Nevan Krogan, Ph.D., joined forces with scientists around the world including with those from UCSF, Gladstone, Icahn School of Medicine at Mount Sinai, Institut Pasteur, and Howard Hughes Medical Institute, to apply their expertise to aid in finding a treatment for the growing pandemic. Together, this team of QBI Coronavirus Research Group (QCRG) researchers was the first to extensively map the protein-protein interaction landscape of SARS-CoV-2 (Gordon et al., 2020).
By focusing on the modification of human proteins that fuel pathology (Wang et al., 2021), QCRG is letting biological interactions dictate the therapeutic target (Gordon et al., 2020).
Utilizing its groundbreaking research, QBI and its collaborators were the first to mechanistically review existing drugs and compounds across the medical landscape, leading to the rapid discovery of 69 agents, which was subsequently expanded to include 97 compounds that have an impact on the identified human proteins. . This breakthrough approach to identify and evaluate the therapeutic efficacy of a wide range of existing therapeutics in a new disease area enables rapid and focused selection of drugs and compounds directed at critical proteins for disease progression (White et al., 2021). Going directly to the chemistry of how drugs interact with the biological target has the potential to lead to faster treatment of patients in a pandemic – where time is paramount – with the drugs with greatest therapeutic potential, either existing or in development.
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 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. UCSF Health, which serves as UCSF’s primary academic medical center, includes top-ranked specialty hospitals and other clinical programs, and has affiliations throughout the Bay Area. Learn more at ucsf.edu or see our Fact Sheet.
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.
Authorship and funding: This work was funded by grants from the National Institute of Mental Health and the National Institute of Allergy and Infectious Diseases, both part of the National Institutes of Health; the Defense Advanced Research Projects Agency; the Center for Research for Influenza Pathogenesis; the Centers of Excellence for Influenza Research and Surveillance of the National Institute of Allergy and Infectious Diseases; the Centers of Excellence for Integrative Biology of Emerging Infectious Diseases of the Agence Nationale de la Recherche (France); F. Hoffmann-LaRoche AG; Vir Biotechnology, Center for Integrative Biological Signaling Studies (CIBSS), European Research Council (ERC) and QCRG philanthropic donors. Shokat is a Howard Hughes Medical Institute investigator. A complete list of authors and full funding information is available in the bioRxiv paper.