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Daily life for many was turned upside down when the coronavirus spread around the world last year and a pandemic was declared.
For Dr Wael Rabeh, an associate professor of chemistry at NYU Abu Dhabi, the global health emergency did not just change his day-to-day activities – it also resulted in a new focus for his research.
Since March 2020, his laboratory has been carrying out work that, it is hoped, will identify drugs that can be used to treat Covid-19 patients.
“When the pandemic started, we thought we should change our role and some of our research activity to focus on the virus,” said Dr Rabeh.
“Treatment is vital, especially for people who cannot take the vaccine or have health issues.”
With two other scientists in his laboratory, and collaborators at other research centres, he has been looking for substances that inhibit a key enzyme - a protein that speeds up biochemical reactions - needed by the coronavirus to generate new virus particles for the infection of other people.
Dr Rabeh’s laboratory has been screening dozens of compounds, many derived from plants and others based on drugs already approved for different uses, to test their effects on an enzyme called 3-chymotrypsin like protease, or 3CLpro.
As its name indicates, this enzyme is a protease, which means that it cuts the bonds between amino acids, the building blocks of proteins.
When the coronavirus replicates, its produces strings of amino acids, and it uses proteases to cut them into individual proteins.
If a drug inhibits the protease, the coronavirus cannot produce the proteins it needs to multiply and assemble new virus particles. This should enable a person with Covid-19 to fight off their infection.
Testing on a live virus
As well as Dr Rabeh, who has worked at NYU Abu Dhabi since it opened in 2010, other researchers across the world are also working to identify substances that inhibit 3CLpro.
Of two chemicals so far pinpointed by Dr Rabeh’s laboratory as being of particular interest, one was the focus of a paper released by another laboratory, causing the Abu Dhabi researchers to end their analysis of it.
A paper on the remaining substance is being prepared, and Dr Rabeh is hoping to collaborate with a laboratory with the biosecurity clearance to carry out studies involving Sars-CoV-2, the virus that causes Covid-19.
This could allow researchers to directly test the effect of the chemical on the live virus, rather than just testing the effect of the chemical on the protease.
Reaching this point has involved studies to work out how the protease functions and to identify the ideal chemical conditions in which to screen substances that could inhibit 3CLpro.
Dr Rabeh and his colleagues have already published three studies as part of this work.
“We look at how the protease works and we use this knowledge to find a specific inhibitor that can target the virus,” said Dr Rabeh.
“If we don’t fully understand how the protease functions, we might not be developing an effective treatment.”
Any inhibitor used as a drug in people should be specific in its actions, targeting 3CLpro but not affecting other proteins in the human body, as doing so could lead to side effects for patients.
Dr Rabeh and his colleagues are continuing with some of their pre-pandemic work, which was focused on cancer, but most of their time is now spent on Covid-19 research.
They were able to change the focus of the laboratory’s work because their funding from NYU Abu Dhabi is flexible and is not tied to a particular project.
While their first study on coronavirus-related work took just a few months to complete and publish, Dr Rabeh said a wave of Covid-related research meant it was now more difficult to get journals to accept papers.
“In the beginning, publishing was easy” he said. “Currently, it’s not as easy as it used to be. Journals are getting thousands of articles. It’s staggering how many publications have come out of this topic.”
