Long before COVID-19 became a part of the global vernacular, it was prominent in Texas A&M University chemist Wenshe Liu’s mind.
Three months ago as the new year dawned, Liu was hard at work on two papers, one published by ChemRxiv in late January that first identified the drug remdesivir — originally developed by Gilead Sciences as the solution for a previous global pandemic in 2014, Ebola — as the only viable medicine for treating SARS-CoV-2, which is the virus that causes COVID-19.
As a chemical biologist specializing in medicinal chemistry, Liu’s primary research target is cancer. However, the late-January lockdown of Wuhan, China, as the epicenter of the looming outbreak in combination with near-simultaneous reports of the first two diagnosed cases in the United States prompted him to double down on his directional efforts. In anticipation of the surreal that soon would become the world’s new normal, he quickly converted the bulk of his research group working on drug discovery for cancer-related causes to the coronavirus front lines.
“The motivation that drove us was the rush against time to find alternative medicines that might be put in use to fight against the virus when it spread to the U.S,” Liu said.
Although many Texas A&M laboratories currently are shut down, Liu’s continues to function with a reduced force consisting only of people directly focused on COVID-19. Specifically, his team is working to develop small-molecule drugs that can prevent SARS-CoV-2 and other coronaviruses from replicating once inside in human cell hosts. They’re also exploring peptide inhibitors with the potential to neutralize SARS-CoV-2 in human plasma. Already, Liu says his group has made significant progress in a very short time toward their ultimate goal: to push a COVID-19 drug candidate to preclinical trials and clinical testing before the pandemic subsides.
“We are not responding passively to the COVID-19 pandemic,” Liu said. “This is the 21st century. We shall not just let nature take its course as it did during the Spanish flu pandemic. There is sufficient scientific knowledge for this group of viruses, and we shall be able to find cures.”
Liu is joined in his work by several additional collaborators in the Department of Chemistry and across the Texas A&M campus, including Distinguished Professor of Chemistry and 2017 National Academy of Sciences member Marcetta Y. Darensbourg, Texas A&M Provost and Executive Vice President and X-ray crystallography expert Carol A. Fierke, and noted Texas A&M biochemist Thomas Meek. Their research is supported by Liu’s Texas A&M Presidential Impact Fellow funds through the Texas A&M Drug Discovery Laboratory as well as indirectly through National Institutes of Health, Cancer Prevention and Research Institute of Texas, and Welch Foundation funding initially provided for his group’s underlying cancer-related research.
Liu notes that remdesivir is being tested in at least five large-scale clinical trials around the world and also has been delivered through a compassionate use program to some patients, including the first known U.S. case confirmed January 21 in Washington. While he remains convinced it’s the right treatment protocol for the moment, he cautions that success shouldn’t be viewed as a one-shot approach, given such a swift-moving target as COVID-19.
“Remdesivir is still the best and probably the only option to target the virus directly in patients,” Liu added. “There are no significant mutations yet found in its targeted gene in the virus. However, given remdesivir’s changed status as an orphan drug for COVID-19, its large-scale use will ensue, and some drug-resistant virus strains will evolve.
“At this stage, the scientific community needs to prepare for the worst and work to bring other make-ready treatment options to the forefront. There have been positive results from a small clinical test in France involving hydroxychloroquinine and its uses in the U.S. Although this is positive progress, additional options are needed.”
When it comes to viral mutations and reports that multiple strains currently exist, Liu defers to the expertise of actual clinicians. However, he does acknowledge one definite distinction he sees in the virus’ present form, compared to that of its recent past during initial outbreak in China late last fall.
“There is one thing that is quite clear to me,” Liu said. “The virus has turned to be more virulent. The infectivity of the original strain shown in Wuhan was not as high as what we have observed for the current strain in the U.S.”
Alongside Liu and his faculty colleagues are dozens of students and postdoctoral researchers who are fully engaged in the effort, including Tyler Lalonde, Trae Hampton, Xinyu Ma, Yuying Ma, Erol Vatansever, Jared Morse, Shiqing Xu, Chia-Chuan Cho, Peng-Hsun Chen, Yugendar Reddy and Kaci Kratch. Liu says he has every confidence in his group’s timely success.
To learn more about the Liu group and related research, visit https://www.chem.tamu.edu/rgroup/liu/.
See a related April 6 news segment from KPRC Channel 2 in Houston.
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Contact: Shana K. Hutchins, (979) 862-1237 or firstname.lastname@example.org or Dr. Wenshe Liu, (979) 845-1746 or email@example.com