Publication in Science reports CABM research that enabled design of drug candidates targeting an Achilles heel of SARS-CoV-2

April 10, 2024
Ashima Chopra, Eddy Arnold, Xavi Ruiz, Ahmad Ansari

Researchers from Rutgers, including the Arnold lab at CABM, are among leaders in a race to find an oral COVID-19 treatment to supplement or replace Paxlovid – the antiviral medication that helps keep high-risk patients out of the hospital and from dying. Their report, published in Science, shows that an alternative medication, a viral papain-like protease (PLpro) inhibitor, inhibits disease progression in animals, a necessary step before human drug trials. 

The Arnold lab was instrumental in the drug design process through determination of structures of PLpro complexed with inhibitors. Research Associate Ahmadullah Ansari determined the structures, with contributions from former Postdoctoral Associate Ashima Chopra (now at Vanderbilt University) and Associate Research Professor Francesc Xavier Ruiz. The last, alongside Board of Governors and Distinguished Professor Eddy Arnold and collaborators Professor Jun Wang (Rutgers, Department of Medicinal Chemistry) and Professor Xufang Deng (Oklahoma State University), designed and supervised the work. Jun Wang is the senior author of this study.

The crystal structures from the Arnold lab showed an unexpected arrangement of how the drug candidate molecules bind to PLpro, leading to innovative design ideas implemented by Professor Wang's medicinal chemistry.  Subsequent testing on SARS-CoV-2-infected mice by Professor Deng's lab at Oklahoma State University showed that oral treatment with Jun12682 reduced viral lung loads and lesions while improving survival rates.

Access full article