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Nature Publication Presents New 'Blueprint' Revealing How SARS-CoV-2 Virus Hijacks Human Cells

Points to Drugs with Potential to Fight COVID-19, and a Drug that Promotes Infection

By UCSF.edu | April 30, 2020

Nature Publication Presents New 'Blueprint' Revealing How SARS-CoV-2 Virus Hijacks Human Cells

Nevan Krogan (center), PhD, and his collaboration of scientists around the world have fast-tracked efforts to find the proteins in cells that get highjacked by COVID-19. Photo by Susan Merrell

An international team of more than 120 scientists has detailed the impact of 75 over-the-counter prescription and development-stage drug compounds on SARS-CoV-2, the virus that causes COVID-19. Several of these agents show promise in blocking SARS-CoV-2 replication in laboratory experiments. One compound investigated in the research, a common ingredient in over-the-counter cough medicines, appears to have the potential to promote the growth of the virus.

The collaborative study, published in Nature on April 30, 2020, was assembled and led by Nevan Krogan, PhD, director of the Quantitative Biosciences Institute at UC San Francisco and a senior investigator at Gladstone Institutes. As the first hints of the pandemic emerged in January, over a matter of just a few weeks, Krogan formed a rapid-response research team of dozens of scientists and clinicians – hailing from UCSF, Gladstone, Icahn School of Medicine at Mount Sinai in New York, and Institut Pasteur in Paris – to search for potential treatments for COVID-19.

Rather than focusing on an antiviral approach to block SARS-CoV-2, the researchers first combined biological and computational techniques to create a “blueprint” of more than 300 human proteins that the virus requires to infect human cells and to thrive and replicate in the body. They then explored the question of which drugs, both those that are currently marketed as well as those in development, might be repurposed to treat SARS-CoV-2 infection by targeting those human proteins.

The researchers emphasize that, while the drugs identified in the study are promising, they have only been tested against the virus in laboratory experiments. The researchers do not advocate anyone prescribing and/or using the drugs unless human clinical trials find them to be safe and effective.

Repurposed Compounds Show Promise for Fighting COVID-19; Further Research Needed

Looking at a list of drugs that interact with the protein blueprint, UCSF researchers Brian Shoichet, PhD, professor of pharmaceutical chemistry, and Kevan Shokat, PhD, professor of cellular and molecular pharmacology and a Howard Hughes Medical Institute investigator, led studies employing chemical biology and computational approaches. Two drug categories emerged as promising agents to effectively reduce viral infectivity: protein translation inhibitors (including zotatifin and ternatin-4/plitidepsin), and drugs that modulate proteins inside the cell known as Sigma1 and Sigma2 receptors (including progesterone, PB28, PD-144418, hydroxychloroquine; the antipsychotic drugs haloperidol and cloperazine; siramesine, an antidepressant and anti-anxiety drug; and the antihistamines clemastine and cloperastine).

 

 

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