A team of researchers at the Quantitative Biosciences Institute at UCSF launched a fast-paced, all-nighter effort in late February to understand how the novel coronavirus functions, and to quickly identify existing drugs that could be used to stop it. Now the team's preliminary findings have been published, and they've identified five drugs with FDA approval to treat other ailments that have shown to be effective antiviral treatments for COVID-19.
The team is led by Canadian-born systems biologist Nevan Krogan, who in February volunteered his lab at UCSF's Mission Bay campus to begin the painstaking process of mapping the human proteins that SARS-CoV-2 needs to replicate itself. Unlike antiviral drugs like Gilead's remdesivir, which has shown promise in disrupting the machinery of the virus, Krogan's work is focused on identifying what the virus needs in host cells to do its dirty work — and by finding drug treatments that disrupt that, he believes the results for the population could be longer-lasting in the event that the virus mutates and becomes drug-resistant.
The Chronicle reported in brief Thursday on the paper published in the journal Nature by Krogan and his colleagues around the globe, and followed up Friday with a long-read about Krogan and the race against the clock that he and his colleagues have been engaged in. Knowing the the university might shut down their lab by mid-March, the team sprinted to do clinical work in support of this paper — work that has previously taken a year or more on other viruses — and to share what they found with other labs and researchers so that the work could be divided up.
Per the Chronicle:
Using cloning techniques, they created copies of the genes, one by one. Then they fashioned each piece of the virus into a kind of hook, lowering the hooks into human cells to see which human proteins got stuck to them. Those were probably the proteins that the virus needed most — and the ones most relevant to disease.
Local billionaire Ron Conway comes into the picture, after Krogan had a previously scheduled call with him on March 12 and the two subsequently worked to raise $5 million of a requested $10 million to cover this research from Silicon Valley donors.
The resulting map is called the virus’ “interactome,” a detailed rundown of 332 interactions between virus proteins and human cell proteins. And the two human proteins that appear to be key in this fight, Sigma R1 and Sigma R2, are according to Krogan "highly druggable."
Now, according to the team's findings, five approved drugs as well as a group of experimental compounds have been shown to be highly effective in lab tests in disrupting these protein interactions. But the team is quick to caution that no one should be using these drugs to treat COVID-19 outside of clinical trials.
One of the drugs they found to be effective is the one touted by President Trump, the anti-malaria drug hydroxychloroquine — however it wasn't the most effective and the team acknowledges that it is also highly toxic to the heart.
The other four approved drugs that showed shocking effectiveness against the virus are haloperidol, a.k.a. Haldol, a drug often used to treat schizophrenia; cloperastine, a common cough suppressant; clemastine, an antihistamine used to treat hay fever and common allergies; and progesterone, the natural hormone that is also used as a medication.
These drugs were among 69 candidates tested in labs in Paris and New York, and out of these tests 10 were found to be effective coronavirus foes — some many times more potent, in fact, than remdesivir.
The experimental compounds, including some used to treat cancers, include one called PB28 which was found to be 20 times more effective in shutting down the virus than hydroxychloroquine and likely not as heart-toxic.
Expect to hear more in the coming months about Krogan and his team's work as clinical trials get underway for these drugs in treating COVID-19. The hope is that, like HIV, a cocktail of treatments will effectively shut down the virus' ability to function in the human body, effectively creating a "cure" before we have a vaccine.
And speaking of HIV, Krogan says that he hopes that ongoing research into curing it and other diseases can happen in the same collaborative, global fashion as this project did — in just three short months.
"The question is, why can’t we do this normally, with other viruses and diseases?" he says to the Chronicle.
