Contemporary approaches to the discovery and development of broad-spectrum natural product prototypes for the control of coronaviruses

George S. Hanna, Yeun-Mun Choo, Ryan Harbit, Heather Paeth, Sarah Wilde, James Mackle, Jacopo-Umberto Verga, Bethany J. Wolf, Olivier P. Thomas, Peter Croot, James Cray, Courtney Thomas, Ling-Zhi Li, Gary Hardiman, Jin-Feng Hu, Xiaojuan Wang, Dharmeshkumar Patel, Raymond F. Schinazi, Barry R. O’Keefe, Mark T. Hamann

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)3001–3007
JournalJournal of Natural Products
Issue number11
Early online date22 Oct 2021
Publication statusPublished - 26 Nov 2021


  • Organic Chemistry
  • Complementary and alternative medicine
  • Drug Discovery
  • Pharmaceutical Science
  • Pharmacology
  • Molecular Medicine
  • Analytical Chemistry


Dive into the research topics of 'Contemporary approaches to the discovery and development of broad-spectrum natural product prototypes for the control of coronaviruses'. Together they form a unique fingerprint.

Cite this