Scaling-up a potential COVID-19 therapy, one molecule at a time

(© stock.adobe.com)

A week after Yale closed its labs to all but the most critical work amid the COVID-19 pandemic, Eric Paulson, director of the Chemical and Biophysical Instrumentation Center (CBIC), got a request.

New England Discovery Partners, a small, contract research firm based in Branford, Connecticut, sought help with a potential therapy for Acute Respiratory Distress Syndrome (ARDS), one of the most severe effects of COVID-19.

When COVID-19 patients develop ARDS, their lungs begin to fill with fluid, restricting the amount of oxygen available to vital organs. They often need a ventilator in order to breathe.

In March, as the pandemic spread across the United States, New England Discovery Partners was working on a clinical trial for a new therapy to treat Irritable Bowel Disease. But the researchers noticed that the same active molecule in their new therapy also seemed to be effective in treating ARDS.

The researchers quickly shifted gears to organize a new clinical trial with their therapy, this time looking specifically at the therapy’s effectiveness against ARDS.

But there was a major problem: The researchers did not have nearly enough of their new molecule. In order to scale-up production they needed access to sophisticated instruments for testing the results of their chemical reactions.

They turned to Yale.

We said yes, of course. This sort of work is exactly what we do,” said Paulson.

The CBIC, located within Yale’s Department of Chemistry on Science Hill, works with a wide spectrum of faculty and student researchers. The center helps researchers study new catalysts, produce novel molecules, and develop new instrumentation. The center even runs samples for undergraduate lab classes.

Historically, we’ve been open 24 hours a day, seven days a week,” Paulson said. “If you’re a trained user of the equipment we have here, you can reserve time on an instrument and have access.”

While the vast majority of CBIC’s work centers on Yale research, the lab also assists a handful of small local companies that need access to expensive scientific instrumentation.

Scaling-up the synthesis of a particular molecule from the gram scale to the kilogram scale is a major undertaking,” Paulson said. “Once you get to the point of testing something on human patients, you need kilograms of the molecule.”

Appreciating the great urgency of COVID-19-related research, Paulson and his CBIC colleagues quickly came up with procedures enabling them to ramp-up testing of the new molecules while also ensuring the health and safety of lab workers.

CBIC crystallographer Brandon Mercado
CBIC crystallographer Brandon Mercado after loading a tray of samples from NEDP into the sample changer of a nuclear magnetic resonance spectrometer.

Each day, one CBIC staff member comes into the lab, minimizing the potential for physical contact that might spread the COVID-19 virus. The staff member works on material for New England Discovery Partners, as well as other critical projects that need maintenance.

For the new COVID-19 therapy, the lab primarily uses its nuclear magnetic resonance spectrometers. These highly specialized instruments analyze the molecular structure and purity of chemical compound samples.

Paulson said it is painstaking work, and the effort to help scale-up the new COVID-19 molecule will continue for several weeks or more.

We’re playing a supporting role in this, but it is no less meaningful,” Paulson said. “It’s a privilege, in fact. Everyone wants to help.”

Share this with Facebook Share this with Twitter Share this with LinkedIn Share this with Email Print this
Part of the In Focus Collection: Yale responds to COVID-19

Media Contact

Fred Mamoun: fred.mamoun@yale.edu, 203-436-2643