COVID-19 Research Responses

Human cells infected with SARS-CoV-2 virus.
NIAID/NIH

School scientists had been monitoring the spread of COVID-19 in the first few months of 2020 before the pandemic took hold in the U.S., enabling numerous labs to quickly pivot to essential research on the disease. The work not only holds promise for treating COVID-19 but will also translate to fending off future threats to human health.

Last updated January 5, 2022.

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Testing for immunity and improving on vaccine delivery and PPE

School faculty members and PhD students are developing tests for COVID-19 immunity, designing new types of personal protective equipment (PPE) for health care workers, and improving vaccine delivery.

A test for immunity

James Wells and colleagues have engineered a variant of a firefly protein to serve as a sensitive, accurate, and rapid test for the antibodies that humans make to fight off COVID-19, which are indicative of immunity to the disease. They are also collaborating with a team at the Chan Zuckerberg BioHub and Zuckerberg San Francisco General Hospital to use this test to measure how long COVID-19 immunity lasts.

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James Wells, PhD, Department of Pharmaceutical Chemistry

Engineering PPE materials and vaccine delivery

Tejal Desai is actively working with collaborators across UCSF to develop nanoparticle-based strategies for a SARS-CoV-2 vaccine. Her lab is also developing ways to give fabrics the filtering capabilities of an N95 mask.

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Tejal Desai, PhD, chair, Department of Bioengineering and Therapeutic Sciences

Personal protective equipment and ICU equipment

Shuvo Roy and colleagues in UCSF Surgical Innovations worked with UCSF clinical engineering and supply chain teams along with UC Berkeley and Yale University engineers to explore concepts for new personal protective equipment (PPE), including 3D-printed face shields and masks. Roy is also looking into ways of repurposing the silicon membranes of the implantable bioartificial kidney, which is in development in his lab, to oxygenate patient blood directly, instead of through the use of mechanical ventilators.

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Shuvo Roy, PhD, Department of Bioengineering and Therapeutic Sciences

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Discovering better therapies for COVID-19

With expertise in countering disease at the molecular level of proteins and genes, our discovery scientists are pursuing new and more effective ways to treat COVID-19. These efforts range from seeking out cures among existing, FDA-approved medications, to hunting for novel drugs that will disrupt the virus’s ability to invade human cells and replicate.

How SARS-CoV-2 affects the heart

Todd McDevitt was investigating how SARS-CoV-2 infection affects laboratory-grown human heart cells and heart tissue. In collaboration with several additional UCSF faculty members, he focused on how the virus enters heart cells via the human ACE2 receptor and exploring ways of disrupting this process.

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Exploring repurposing of hypertension medications for COVID-19

Su Guo is investigating the relationship between certain medications used for the treatment of hypertension (high blood pressure), heart failure, and COVID-19. She is looking into how anti-hypertensive medications (ACEI and ARBs) interact with the gene ACE2, which is responsible for COVID-19 entry into cells.

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Su Guo, PhD, Department of Pharmaceutical Chemistry

Harnessing innate immunity to counter SARS-CoV-2

John Gross is studying how SARS-CoV-2 suppresses the human immune processes that normally prevent viral infection. He is focusing on how coronaviruses shut off gene expression and co-opt the protein degradation machinery in human cells.

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John Gross, PhD, Department of Pharmaceutical Chemistry

Decoy proteins for fighting SARS-CoV-2 infection

The laboratories of Tanja Kortemme and James Wells have designed high-affinity proteins and protein fragments that bind tightly to the SARS-CoV-2 “spike” protein, which is used by the virus to infect human cells. These molecules neutralize the virus in cell culture as potently as high-affinity antibodies, and are promising therapeutic candidates for further testing in animal models and as a potential aerosol drug.

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Papers

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QBI Coronavirus Research Group (QCRG)

Media coverage

Jamming the gears of a deadly virus (UCSF School of Pharmacy)

Integrative structure determination of SARS-CoV-2-human protein complexes

Andrej Sali is investigating the structures of the protein complexes formed by SARS-CoV-2 proteins and human proteins, with the goal of understanding the role of these complexes during viral entry into human cells and viral replication.

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Andrej Sali, PhD, Department of Bioengineering and Therapeutic Sciences

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QBI Coronavirus Research Group (QCRG)

Crystallographic fragment screen of SARS-CoV-2 macrodomain

James Fraser is developing inhibitors of a SARS-CoV-2 protein called the macrodomain. In collaboration with researchers at the Advanced Light Source at Berkeley Lab and the Stanford Synchrotron Radiation Lightsource at the SLAC National Accelerator Laboratory, Fraser used X-ray crystallography to map the structure of the macrodomain, and then tested the ability of hundreds of small chemical fragments to bind to the protein. The data from this project has been made public and Fraser is now using these fragments to build a drug to prevent the virus from replicating in human cells.

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James Fraser, PhD, Department of Bioengineering and Therapeutic Sciences

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QBI Coronavirus Research Group (QCRG)

Media coverage

Therapeutics aimed at the corona of the novel coronavirus

William DeGrado is developing proteins that bind to the spike and envelope proteins that encase the SARS-CoV-2 virus. The work may lead to improved diagnostics for active infection and new therapeutics.

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William DeGrado, PhD, Department of Pharmaceutical Chemistry

Website

QBI Coronavirus Research Group (QCRG)

The role of protein degradation in SARS-CoV-2 infection

Charles Craik is studying how viral and human proteases (enzymes that break down other proteins) are used during SARS-CoV-2 replication. Two proteases of interest include 3CLPro, a major viral protease, and TMPRSS2, a host protease that is involved in virus entry. He is also working on approaches for detection of neutralizing antibodies to the virus, found in patients with COVID-19, as well as inhibitory antibodies for passive immunization and a safe version of the virus for active immunization.

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Charles Craik, PhD, Department of Pharmaceutical Chemistry

Website

QBI Coronavirus Research Group (QCRG)

Nanobody-based antiviral blocks SARS-CoV-2 in the lab

Researchers at UCSF developed an antiviral therapy that may be effective in slowing the spread of the COVID-19 pandemic. The team, led by Aashish Manglik, Peter Walter, and graduate students from both of their labs, sifted through a library of 2 billion nanobodies (small, antibody-like molecules) to identify those that blocked the SARS-CoV-2 spike protein. With help from collaborators at the Institut Pasteur in Paris, the group created a cocktail of nanobodies optimized for the highest potency against the virus, and showed its effectiveness against the virus in the lab when formulated as an aerosol spray.

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Media coverage

‘AeroNabs’ Promise Powerful, Inhalable Protection Against COVID-19 (UCSF News)

Choosing the most promising COVID-19 drug candidates with machine learning

Michael Keiser and Luca Ponzoni are developing a new system for analyzing the 3D interactions between COVID-19 drug candidates and their viral or human host protein targets. The work, carried out in collaboration with the Accelerating Therapeutics for Opportunities in Medicine (ATOM) consortium and QCRG, will enable scientists to use machine learning to more precisely prioritize these drug candidates for laboratory testing, and eventually clinical trials.

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Collaborating to find cures among existing medications

The Quantitative Biosciences Institute (QBI), helmed by Director Nevan Krogan, has mobilized over 40 UCSF faculty members to find already-available drugs that might interfere with how the SARS-CoV-2 virus uses human cells in an infection. The group, dubbed the QBI Coronavirus Research Group (QCRG), initially identified 69 candidate drugs, 49 of which were then tested for activity against live SARS-CoV-2 by collaborating labs. Five FDA-approved medications, which were originally designed to treat conditions as varied as malaria and mental illness, were effective against SARS-CoV-2 in the lab, along with a number of experimental therapies that have yet to be approved. The next step for the research will involve testing these drugs in animal models of COVID-19 and eventually clinical trials with human subjects.

More recently, QCRG led an effort to understand how the Alpha variant of SARS-CoV-2 evolved to be more infectious than its predecessor. The group found that mutations in certain viral proteins enabled Alpha to block aspects of the human immune response, and that the Delta and Omicron variants shared these same mutations. The work points to new avenues for developing therapies against current and future variants of the coronavirus.

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Websites

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