Zinuo Chen1, Qinghua Cui1,2,3, Laura Cooper4, Pin Zhang5, Hyun Lee6, Zhaoyu Chen1, Yanyan Wang1, Xiaoyun Liu2, Lijun Rong7, Ruikun Du8,9,10. 1. College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China. 2. Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China. 3. Qingdao Academy of Chinese Medicinal Sciences, Shandong University of Traditional Chinese Medicine, Qingdao, 266122, China. 4. Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, IL, 60612, USA. 5. Chicago BioSolutions Inc, 2242 W Harrison Street, Chicago, Illinois, 60612, United States. 6. Department of Pharmaceutical Sciences, Center for Biomolecular Sciences, College of Pharmacy, Biophysics Core at Research Resources Center, University of Illinois at Chicago, Chicago, IL, 60607, USA. 7. Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, IL, 60612, USA. lijun@uic.edu. 8. College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China. duzi857@163.com. 9. Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China. duzi857@163.com. 10. Qingdao Academy of Chinese Medicinal Sciences, Shandong University of Traditional Chinese Medicine, Qingdao, 266122, China. duzi857@163.com.
Abstract
BACKGROUND: In the urgent campaign to develop therapeutics against SARS-CoV-2, natural products have been an important source of new lead compounds. RESULTS: We herein identified two natural products, ginkgolic acid and anacardic acid, as inhibitors using a high-throughput screen targeting the SARS-CoV-2 papain-like protease (PLpro). Moreover, our study demonstrated that the two hit compounds are dual inhibitors targeting the SARS-CoV-2 3-chymotrypsin-like protease (3CLpro) in addition to PLpro. A mechanism of action study using enzyme kinetics further characterized the two compounds as irreversible inhibitors against both 3CLpro and PLpro. Significantly, both identified compounds inhibit SARS-CoV-2 replication in vitro at nontoxic concentrations. CONCLUSIONS: Our finding provides two novel natural products as promising SARS-CoV-2 antivirals.
BACKGROUND: In the urgent campaign to develop therapeutics against SARS-CoV-2, natural products have been an important source of new lead compounds. RESULTS: We herein identified two natural products, ginkgolic acid and anacardic acid, as inhibitors using a high-throughput screen targeting the SARS-CoV-2 papain-like protease (PLpro). Moreover, our study demonstrated that the two hit compounds are dual inhibitors targeting the SARS-CoV-2 3-chymotrypsin-like protease (3CLpro) in addition to PLpro. A mechanism of action study using enzyme kinetics further characterized the two compounds as irreversible inhibitors against both 3CLpro and PLpro. Significantly, both identified compounds inhibit SARS-CoV-2 replication in vitro at nontoxic concentrations. CONCLUSIONS: Our finding provides two novel natural products as promising SARS-CoV-2 antivirals.
Authors: Lennart Brewitz; Jos J A G Kamps; Petra Lukacik; Claire Strain-Damerell; Yilin Zhao; Anthony Tumber; Tika R Malla; Allen M Orville; Martin A Walsh; Christopher J Schofield Journal: ChemMedChem Date: 2022-02-17 Impact factor: 3.540
Authors: Veronica Di Sarno; Gianluigi Lauro; Simona Musella; Tania Ciaglia; Vincenzo Vestuto; Marina Sala; Maria Carmina Scala; Gerardina Smaldone; Francesca Di Matteo; Sara Novi; Mario Felice Tecce; Ornella Moltedo; Giuseppe Bifulco; Pietro Campiglia; Isabel M Gomez-Monterrey; Robert Snoeck; Graciela Andrei; Carmine Ostacolo; Alessia Bertamino Journal: Eur J Med Chem Date: 2021-09-22 Impact factor: 6.514