Contemporary Approaches to the Discovery and Development of Broad-Spectrum Natural Product Prototypes for the Control of Coronaviruses

• Type of Material: Article
• Authors: George S. Hanna, Medical University of South Carolina; Yeun-Mun Choo, Universiti Malaya; Ryan Harbit, College of Charleston; Heather Paeth, Medical University of South Carolina; Sarah Wilde, Clemson University; James Mackle, Queens University; Jacopo-Umberto Verga, Queens University; Bethany J. Wolf, Medical University of South Carolina; Olivier P. Thomas, National University of Ireland Galway; Peter Croot, National University of Ireland; James Cray, Ohio State University; Courtney Thomas, South Carolina State University; Ling-Zhi Li, Shenyang Pharmaceutical University; Gary Hardiman, Queens University; Jin-Feng Hu, Taizhou University; Xiaojuan Wang, Lanzhou University; Dharmeshkumar Patel, Emory University; Raymond Schinazi, Emory University; Barry R. O'Keefe, National Cancer Institute; Mark T. Hamann, Medical University of South Carolina
• Language: English
• Date: 2021-10-22
• Publisher: AMER CHEMICAL SOC
• Publication Version: Final Published Version
• Copyright Statement: © 2021 American Chemical Society and American Society of Pharmacognosy
• Final Published Version (URL): http://dx.doi.org/10.1021/acs.jnatprod.1c00625
• Title of Journal or Parent Work: JOURNAL OF NATURAL PRODUCTS
• Volume: 84
• Issue: 11
• Start Page: 3001
• End Page: 3007
• Grant/Funding Information: G.S.H. acknowledges support from NIH/NCCIH 1F31AT011158-01 for Fellowship funding. M.T.H. acknowledges support from the South Carolina SmartState Program and The Abney Foundation. G.H. acknowledges support from NIH U54MD010706, U01DA045300, and QUB start-up funds. J.M. was supported by an NI Department for the Economy (DfE) Research Studentship. J.U.V. was the recipient of an ERASMUS Student Mobility Traineeship. Part of this project (Grant-Aid Agreement Nos. PBA/MB/16/01 and PDOC/19/02/01) was carried out with the support of the Marine Institute and is funded under the Marine Research Program by the Irish Government. R.F.S. is supported in part by the Center for AIDS Research at Emory University (P30-AI-050409).
• Keywords: Chemistry, Medicinal; Pharmacology & Pharmacy; SARS-COV-2; Science & Technology; Life Sciences & Biomedicine; SPIKE; Plant Sciences; MOLECULAR NETWORKING
• Research Categories: Biology, Virology; Health Sciences, Pharmacology; Chemistry, Pharmaceutical

Abstract

The pressing need for SARS-CoV-2 controls has led to a reassessment of strategies to identify and develop natural product inhibitors of zoonotic, highly virulent, and rapidly emerging viruses. This review article addresses how contemporary approaches involving computational chemistry, natural product (NP) and protein databases, and mass spectrometry (MS) derived target-ligand interaction analysis can be utilized to expedite the interrogation of NP structures while minimizing the time and expense of extraction, purification, and screening in BioSafety Laboratories (BSL)3 laboratories. The unparalleled structural diversity and complexity of NPs is an extraordinary resource for the discovery and development of broad-spectrum inhibitors of viral genera, including Betacoronavirus, which contains MERS, SARS, SARS-CoV-2, and the common cold. There are two key technological advances that have created unique opportunities for the identification of NP prototypes with greater efficiency: (1) the application of structural databases for NPs and target proteins and (2) the application of modern MS techniques to assess protein-ligand interactions directly from NP extracts. These approaches, developed over years, now allow for the identification and isolation of unique antiviral ligands without the immediate need for BSL3 facilities. Overall, the goal is to improve the success rate of NP-based screening by focusing resources on source materials with a higher likelihood of success, while simultaneously providing opportunities for the discovery of novel ligands to selectively target proteins involved in viral infection.