UCSF & Collaborators Identify Existing Drugs that Show More Potential Against SARS-CoV-2

UCSF & Collaborators Identify Existing Drugs that Show more Potential against SARS-CoV-2

Scientists at the University of California, San Francisco (UCSF) Quantitative Biosciences Institute (QBI) worked in obscurity for many years delving deeply into how different classes and types of pathogens interact with human proteins, all in the hope of someday finding superior treatments for disease. With the advent of the COVID-19 pandemic, QBI Director Kevan Krogan, PhD, rallied 100 researchers at UCSF and beyond to apply their expertise to the imminent pandemic. Now the QBI Coronavirus Research Group (QCRG), along with a number of prominent collaborators, produced serious results identifying nearly 70 potential drug candidates that could target SARS-CoV-2 as identified by TrialSite News April 2020. A group of authors associated with the collaboration recently published their findings in Nature: they now report they have identified 66 druggable human proteins or host factors targeted by 69 compounds (29 FDA-approved drugs, 12 drugs in clinical trials and 28 preclinical compounds). Could this work lead to a direct treatment to COVID-19? What are these compounds?

Preventing the Virus from Multiplying

According to the recent QBI findings, there are 10 drug compounds that could be effective at stopping the novel coronavirus from multiplying within the body based on the study from scientists in America and France. After further scrutinizing how the human proteins and the virus interact when the body’s cells are infected—and hence start multiplying—the team drilled into compounds that could block the virus from using those particular proteins. Their findings: 47 compounds in cell cultures that could drive the desired effect and 10 of those already are represented in approved drugs or under investigation for a diverse array of conditions. It could be possible these drugs could be repurposed to target SARS-CoV-2. This dovetails with a flurry of activity where academic medical centers and pharma and biotech companies are in a race to explore the repurposing of drugs, including Gilead’s experimental remdesivir, to target the novel coronavirus.

Some Potential Drugs

Plitidepsin, utilized in an investigational oncology therapy known as Aplidin, is currently under investigation for COVID-19 in Spain. Progesterone, a hormone, acts against the novel coronavirus, which could offer clues to why men could be more susceptible to SARS-Cov-2. The group uncovered a number of candidates for repurposing such as clemastine, an antipsychotic haloperidol as well as malarial drug hydroxychloroquine—they did find that this anti-malarial could have toxic side effects on the heart. Another target is an experimental chemical called PB28, which they found was 20-times more potent than hydroxychloroquine in targeting the receptor and less affinity toward the heart protein.

Far more Potent than the “Standard of Care”

Nevan Krogan from QBI (UCSF) noted in a recent media presentation, “Some of our drugs and compounds are many times more potent than remdesivir, at least in a laboratory setting.” Hence, the QBI team (and collaborators) will continue to investigate candidates identified by the group.

Lead Research/Investigator (Authors)

David E. Gordon 

Gwendolyn M. Jang 

Mehdi Bouhaddou 

Jiewei Xu 

Kirsten Obernier 

Kris M. White 

Matthew J. O’Meara 

Veronica V. Rezelj