Affiliations 

  • 1 Departments of Drug Discovery and Biomedical Sciences and Public Health, Colleges of Pharmacy and Medicine, Medical University of South Carolina, Charleston, South Carolina 29425, United States
  • 2 Department of Chemistry, University of Malaya, Kuala Lumpur 50603, Malaysia
  • 3 College of Charleston, Charleston, South Carolina 29425, United States
  • 4 Department of Biology, Clemson University, Clemson, South Carolina 29631, United States
  • 5 School of Biological Sciences & Institute for Global Food Security, Queens University, Belfast, Northern Ireland BT7 1NN, United Kingdom
  • 6 Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina 29425, United States
  • 7 Marine Biodiscovery, School of Chemistry and Ryan Institute, National University of Ireland Galway, Galway H91Tk33, Ireland
  • 8 Irish Centre for Research in Applied Geoscience, Earth and Ocean Sciences and Ryan Institute, School of Natural Sciences, National University of Ireland, Galway, Galway H91Tk33, Ireland
  • 9 Department of Biomedical Education and Anatomy, College of Medicine and Division of Biosciences, College of Dentistry, The Ohio State University, Columbus, Ohio 43210, United States
  • 10 Department of Chemistry, South Carolina State University, Orangeburg, South Carolina 29117, United States
  • 11 School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University/SPU, Shenyang 110016, China
  • 12 School of Advanced Study, Zhejiang Provincial Key Laboratory of Plant Ecology and Conservation, Taizhou University, Zhejiang 318000, China
  • 13 School of Pharmacy, Lanzhou University, Lanzhou 730300, China
  • 14 Department of Pediatrics, Laboratory of Biochemical Pharmacology, Emory University School of Medicine, and Children's Healthcare of Atlanta, Atlanta, Georgia 30322, United States
  • 15 Molecular Targets Program, Center for Cancer Research, Natural Products Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Frederick, Maryland 21702, United States
J Nat Prod, 2021 Nov 26;84(11):3001-3007.
PMID: 34677966 DOI: 10.1021/acs.jnatprod.1c00625

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.