Campus & Community University News Research Events People About Taking antiviral aim to stop COVID-19 and possible future viruses in their tracks DECEMBER 2, 2021HEALTH & WELLNESSNEW FEATURERESEARCHSCIENCE & TECH Researchers at Case Western Reserve University, Duke and Rutgers lead work to understand how the novel coronavirus’s tangled RNA could help treat infected people Scientists at Case Western Reserve, Duke, and Rutgers universities have identified compounds within the coronavirus genome that have the potential to block its ability to replicate. Their findings appeared Friday, Nov. 26, in the journal Science Advances. Blanton Tolbert “We reasoned that the unique shape of the virus’s RNA genome presented an opportunity to target it with small molecules that might hold potential to slow the virus’s ability to spread,” said Blanton S. Tolbert, the Rudolph and Susan Rense Professor of Chemistry at Case Western Reserve, one of the researchers leading the project. “And the early results are encouraging.” Amanda Hargrove, a chemistry professor at Duke University, said in a news release that the work offered an untapped therapeutic potential to fight COVID-19: “These are the first molecules with antiviral activity that target the virus’s RNA specifically, so it’s a totally new mechanism in that sense,” she said. Tolbert and Hargrove are joined in the work by molecular biologist and virologist Gary Brewer and molecular biologist Mei-Ling Li, both of Rutgers. Other collaborators included researchers from the Washington University School of Medicine in St. Louis, the University of Nebraska-Lincoln, the University of Michigan, and the University of Glasgow. The researchers also noted that the discovery could lead to treatments for other future viruses. They determined that the loops and bulges of RNA that they identified have remained essentially unchanged by evolution across related coronaviruses in bats, rats and humans, including those that caused the SARS and MERS outbreaks. Tolbert said the collaboration began in February 2020 at an informal meeting among the three main research groups from CWRU, Duke and Rutgers at Duke University. “We laid out the first steps to inhibit SARS-CoV-2,” he said, “because the group anticipated that the virus might become a bigger public health concern than it was initially perceived.” Other Case Western Reserve researchers involved were all from Tolbert’s lab: postdoctoral student Le Luo; and graduate students Christina Haddad, Jesse Davila-Calderon and Liang Yuan-Chiu, who has since graduated. A better antiviral? To infect cells, the coronavirus must break in, deliver its genetic instructions in the form of RNA, and hijack that cell’s molecular machinery to build new copies of itself. The infected cell becomes a virus factory, reading the 30,000 nucleotide “letters” of the virus’s genetic code and churning out the proteins needed for the virus to replicate and spread. Most antivirals—including remdesivir and molnupiravir, the only antiviral drugs that the U.S. Food and Drug Administration has approved or is considering for approval to protect against COVID-19 work by binding to these proteins. But Tolbert, Hargrove and their team have taken a different approach. They’ve identified the first molecules that can take aim at the folds of RNA strands found in the complex 3D structure of the viral genome itself. Building on early research This new work builds on research first conducted by Hargrove, Tolbert and others in 2020, just as the COVID-19 pandemic started to make headlines. That team was already investigating potential drug candidates to fight another RNA virus—Enterovirus 71, a common cause of hand, foot and mouth disease in children. The group had identified a class of small molecules called amilorides that can bind to hairpin-like folds in the virus’s genetic material and disrupt its replication. Using computer modeling and a technique called nuclear magnetic resonance spectroscopy, the researchers were able to analyze these 3D RNA structures and pinpoint where the chemical compounds were binding. The researchers have a patent pending on their method and intend to modify the compounds to make them more potent, and then conduct animal testing “to see if this could be a viable drug candidate,” Hargrove said. For more information, contact Mike Scott at mike.scott@case.edu. This article was originally published Nov. 29, 2021. ANTIVIRALBLANTON TOLBERTCOLLEGE OF ARTS AND SCIENCESCORONAVIRUSCOVID-19DEPARTMENT OF CHEMISTRYRELEASERNA RELATED POSTS Art Studio: Fall Semester-in-Review opening DECEMBER 3, 2021 Get your COVID-19 booster, flu shot on campus before winter break DECEMBER 2, 2021 ARCHIVES Select Month December 2021 November 2021 October 2021 September 2021 August 2021 July 2021 June 2021 May 2021 April 2021 March 2021 February 2021 January 2021 December 2020 November 2020 October 2020 September 2020 August 2020 July 2020 June 2020 May 2020 April 2020 March 2020 February 2020 January 2020 December 2019 November 2019 October 2019 September 2019 August 2019 July 2019 June 2019 May 2019 April 2019 March 2019 February 2019 January 2019 December 2018 November 2018 October 2018 September 2018 August 2018 July 2018 June 2018 May 2018 April 2018 March 2018 February 2018 January 2018 December 2017 November 2017 October 2017 September 2017 August 2017 July 2017 June 2017 May 2017 April 2017 March 2017 February 2017 January 2017 December 2016 November 2016 October 2016 September 2016 August 2016 July 2016 June 2016 May 2016 April 2016 March 2016 February 2016 January 2016 December 2015 November 2015 October 2015 September 2015 August 2015 July 2015 June 2015 May 2015 April 2015 March 2015 February 2015 January 2015 December 2014 November 2014 October 2014 September 2014 August 2014 July 2014 June 2014 May 2014 April 2014 March 2014 February 2014 January 2014 December 2013 November 2013 October 2013 September 2013 August 2013 July 2013 June 2013 May 2013 April 2013 March 2013 February 2013 January 2013 December 2012 November 2012 October 2012 September 2012 August 2012 July 2012 June 2012 May 2012 April 2012 March 2012 February 2012 January 2012 December 2011 November 2011 October 2011 September 2011 August 2011 July 2011 June 2011 May 2011 UPCOMING EVENTS Doc Opera: “GARLA La Land” Art Studio: Fall Semester-in-Review opening PRCHN Seminar Series: “Local Policies and Interventions to Address Diet-Related Health Disparities” View all Events RECENTLY FEATURED Support CWRU organizations and initiatives during #GivingTuesdayatCWRU NOVEMBER 29, 2021 CWRU partners with Cleveland Metropolitan School District to provide COVID-19 vaccines to local families NOVEMBER 24, 2021 View all Recently Featured LIFE @CWRU © 2017 Case Western Reserve University 10900 Euclid Ave. Cleveland, Ohio 44106 216.368.2000 (legal notice) SUBMIT TO THE DAILY Submit an Article Editorial Guidelines SUBSCRIBE Subscribe to The Daily FOLLOW US