Faculty and students at IUPUI are working on new ways to treat SARS-CoV-2, the virus causing COVID-19. Bill Scott, a research professor at the IUPUI School of Science, and his team have developed synthetic procedures to make numerous molecules to treat infections of both existing and mutated forms of SARS-CoV-2.
The molecules created by Scott and his team inhibit Mpro, the main proteolytic enzyme required for viral replication of SARS-CoV-2. Blocking this enzyme slows the spread of infection.
The current treatment for COVID-19 is Paxlovid, Pfizer’s two-drug combination comprised of nirmatrelvir and ritonavir. Nirmatrelvir, the key ingredient of Paxlovid, inhibits Mpro, and ritonavir slows the rapid metabolism of nirmatrelvir so the drug can stay in the blood stream longer.
While Paxlovid reduces COVID-19 symptoms and lessens the likelihood of hospitalizations, the drug’s utility may change with future COVID variants. Thus, Scott and his team are continually creating and evaluating the array of Mpro inhibitors to find candidates with improved activity against current and future mutated forms of SARS-CoV-2.
“We know that as viruses mutate, they sometimes become resistant to current treatments,” Scott said. “I am afraid that at some point this will become true for nirmatrelvir, so we want to be prepared with the library of drug candidates.”
Scott and his team also aim to design Mpro inhibitors with improved stability, eliminating the need for ritonavir to be co-administered and avoiding its potentially harmful side effects.
“As wonderful as Paxlovid is, the ritonavir it contains, with its side effects, prevents some people from using it,” Scott said. “A more metabolically stable Mpro inhibitor will enable the successful treatment of many more patients with COVID-19.”
This initiative began under Scott’s Distributed Drug Discovery Program (D3), which aims to teach chemistry, biology and computational analysis to a community of students across the world by synthesizing and screening drug candidates to treat neglected and infectious diseases.
Scott has worked with the IU Innovation and Commercialization Office (ICO) for numerous inventions and is seeking partnerships to support the D3 program and translate the Mpro inhibitor library. He worked at Eli Lilly as a research scientist in drug discovery from 1974 to 2001. He joined the IUPUI faculty in 2002.
Bri Heron, technology marketing manager at Indiana University’s Innovation and Commercialization Office, contributed the following story.
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