Thursday, March 26, 2020

Virologist optimistic on finding effective drugs

Equipment can test thousands of compounds quickly,
program up and running after city's red-tape delays


A photo of BU NEIDL virologist Robert Davey
Robert Davey holds vials of the Covid-19 virus, which are carefully packed into the container he is holding. His Boston University lab team is used to wearing full biocontainment suits for work on far deadlier viruses, like Ebola. So although the novel coronavirus can safely be worked on at a Biosafety Level 3 facility, his crew in the highest possible containment setting, the NEIDL Biosafety Level 4 lab.
Photo by Callie Donahue, Boston University


A Boston University virologist who is launching the testing of a large batch of potentially life-saving drugs against a live sample of the coronavirus is "very optimistic" that an effective treatment will be found "as quickly as possible."

Robert Davey, a virologist, received the green light to begin screening potentially life-saving drug candidates against live Sars-Cov-2, the virus that triggers the Covid-19 disease, the university has announced.

Davey is confident that good news is on the way. “Undeniably, we will identify something that has reasonable potency against the novel coronavirus,” he says. “Getting something with high potency is harder, but that’s where great chemists come into play.”

"We will take drugs that are already out there on the market to test them and see if they are effective, and then we're going to test new chemicals to see if they have any ability," Davey told a newsman. "I'm very optimistic we can find something as quickly as possible."

"We're one of the handful of labs around the country that can screen thousands of drugs to find a treatment for this disease," he added. The research is similar to large-scale drug studies being conducted by Scripps Research.

"We learned how to grow the virus, it’s good to get to know your enemy, and we will start testing on human cells ... as soon as this Friday," he said. "We are very hopeful that things will work."

Asked by a TV reporter whether the anti-malarial drugs touted by President Trump would be included in his research, Davey said they are "in the library that we are testing" but hopes to find a more effective cure.

"They are in the library that we are testing but there could be many others out there that could be even better than them," he said, referring to hydroxychloroquine and the antibiotic azithromycin.

Davey and his team of scientists at Boston University’s National Emerging Infectious Diseases Laboratories (NEIDL), this week started suiting up to conduct research on live samples of the novel coronavirus.

This type of emergency—a fast-spreading virus outbreak—is precisely what the NEIDL, now in its second year of full operation, was made for, a university statement says. NEIDL’s work will involve a number of studies scientists are planning related to Sars-CoV-2, the virus that triggers the disease called Covid-19.

Davey’s team will be pitting tens of thousands of drugs against lab cultures of cells infected with contagions, permitting rapid detection of which drugs are most effective at halting or reducing infection. It should take only a few weeks to earmark the most effective drugs, the university said.

Typically, Davey’s team handles some of the world’s most lethal diseases, like Ebola or Marburg fevers, inside a Biosafety Level 4 (BSL-4) laboratory, which has the highest possible level of biosafety containment used for infectious agents that pose especially high risk to humans. At the NEIDL, Davey and crew members routinely wear biocontainment garb -- often known as "moon suits."

Although some people might find the suits claustrophobic, Davey’s team has become more comfortable working inside the suits than outside. So, even though SARS-Cov-2 requires only a BSL-3 lab—no moon suits needed—Davey and his team will treat it just as they would a far deadlier pathogen like Ebola.

In addition, the moon suits can be used instead of other personal protective gear, which is in short supply all across the country/

It has taken Davey and NEIDL colleagues weeks to prod Boston's public health officials to grant approvals for their life-saving work.

The list of requirements that must be met for work to begin on any new pathogen is daunting and the NEIDL team has been "flying at breakneck pace since January" to get its official letter of approval from the Boston Public Health Commission, the university said.

“To get to this point was a huge effort where many people went out of their way to make it happen,” Davey says. “We did everything by the book to make sure we are working safely.” Davey's lab, will use small and efficient robots to overcome "traditional bottlenecks and inefficiencies of working with live cultures, to help them simultaneously evaluate potential drug compounds on 384 different wells of human lung cells infected with Sars-Cov-2," the university said.

“Compounds stick to, or get in between, virus proteins like a wedge, blocking them from coming together and functioning properly,” Davey says.

Inside the culture plates, the researchers will dose Sars-CoV-2–infected lung cells with a huge variety of compounds, he says. Some concoctions are derived from already-FDA-approved antiviral medications—which would make for an especially quick path toward approval for use in humans infected with Covid-19—and some are completely novel drug candidates designed by chemists working with John Porco, director of BU’s Center for Molecular Discovery (BU-CMD).

The NEIDL is among only a handful of facilities in the United States with both BSL-3 and BSL-4 facilities. And so far, partly because of the shortage of BSL-3 gear, it’s the only site in Boston that has the potential to work on live coronavirus.

“We maintain a chemical collection of thousands of compounds designed for a variety of biological uses,” Porco says. “We’ve given the NEIDL—with which we’ve had a long-standing collaboration to develop antiviral agents—our entire collection to test against the novel coronavirus. We think there will be some interesting drug candidates that emerge from this screen.”

Davey says his team will be watching the infected lung cell cultures closely to see how Sars-CoV-2 responds to each different compound from the Molecular Center. Some compounds are designed to block viruses from entering host cells, and others interfere with a virus’s ability to replicate its genetic material. Still others scramble a virus’s ability to assemble itself and proliferate infection after it’s released from dead host cells.

“Our goal is to find drugs that can reduce viral burden and alleviate the highest levels of infection,” Davey says. “The gold standard would be to find small molecules that halt Covid-19 in its tracks and prevent it from transmitting. To get there, of course, is hard. We have to be careful that these molecules don’t otherwise affect a person’s health or cause unintended side effects.”

In addition, Davey and Porco are collaborating to try to fine-tune promising compounds to increase their effectiveness against Covid-19, without causing side effects, however they can. Porco and his team at BU-CMD also specialize in small molecules called macrocycles—chemical compounds that fit into receptors on the surfaces of viruses like a key fits into a lock, blocking other molecular machinery from gaining entry as long as they stay fitted in place.

“Between basic chemistry and drug discovery efforts and the NEIDL, BU is in a great position to be working on COVID-19,” Porco says.

Federal science agencies are rolling out funding calls for Covid-19-related research. Research is being encouraged by the Centers for Disease Control and Prevention, the National Institutes of Health, the National Science Foundation and the Departments of Defense, Energy and Health and Human Services.
Elements of this story appeared on Fox News.

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