Keynote Presentation: The formation of an International Collaborative Network to find COVID-19 Therapeutics

The Quantitative Biosciences Institute (QBI) at UCSF is an institute that focuses on collaborations and established itself as an important hub for novel biomedical research and technology development both domestically and internationally. QBI has also become synonymous with collaborations across the globe to bring scientists together, and as a result was perfectly situated for the formation of the QBI Coronavirus Research Group (QCRG).

For the first time, forty-two leading laboratories, involving hundreds of scientists within the Quantitative Biosciences Institute (QBI) at the University of California, San Francisco (UCSF), are combining their efforts, technologies and expertise to fight the coronavirus pandemic. Many of our laboratories have previously collaborated in the investigation of other human pathogens including HIV, Ebola, Dengue, Zika, Herpesvirus, Hepatitis C, Tuberculosis, Chlamydia and West Nile Fever, revealing impactful new ways to treat these diseases.

The newly formed QCRG (QBI Coronavirus Research Group) is bringing together expertise in biochemistry, virology, structural, computational, chemical and systems biology to understand how SARS-CoV-2 hijacks human cells for its own replication and rapidly develop treatments. We are using a combination of mass spectrometry, CRISPR-based genetics and structural analysis through Cryo-EM to systematically generate a viral-human interaction map involving all 29 SARS-CoV-2 proteins.

We identified 66 druggable human proteins at the virus-host interface, targeted by 69 compounds (of which, 29 drugs are approved by the US Food and Drug Administration, 12 are in clinical trials and 28 are preclinical compounds).

In a separate study building on these results, we created a quantitative mass spectrometry-based phosphoproteomics survey of SARS-CoV-2 infection in cell culture. We identified 87 drugs and compounds by mapping global phosphorylation profiles to dysregulated kinases and pathways. Pharmacologic inhibition of p38, CK2, CDKs, AXL and PIKFYVE kinases possessed antiviral efficacy, representing potential COVID-19 therapies. Clinical trials with some drugs and compounds implicated by our studies are currently being discussed or are already underway.

Learning Objectives:

1. Understanding the integral value of collaboration for advancement in scientific research; how to establish and grow academic, Pharma, and industry connections

2. Learn about how the coronavirus hijacks and re-wires our genes and proteins during infection

3. How to integrate different datatypes to derive informed testable hypothesis relating to COVID-19

4. How to identify potential therapeutics that can inform clinical trials