Identification of existing pharmaceuticals and herbal medicines as inhibitors of SARS-CoV-2 infection
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Open Access
- 15 January 2021
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 118 (5)
- https://doi.org/10.1073/pnas.2021579118
Abstract
The outbreak of COVID-19 caused by SARS-CoV-2 has resulted in more than 50 million confirmed cases and over 1 million deaths worldwide as of November 2020. Currently, there are no effective antivirals approved by the Food and Drug Administration to contain this pandemic except the antiviral agent remdesivir. In addition, the trimeric spike protein on the viral surface is highly glycosylated and almost 200,000 variants with mutations at more than 1,000 positions in its 1,273 amino acid sequence were reported, posing a major challenge in the development of antibodies and vaccines. It is therefore urgently needed to have alternative and timely treatments for the disease. In this study, we used a cell-based infection assay to screen more than 3,000 agents used in humans and animals, including 2,855 small molecules and 190 traditional herbal medicines, and identified 15 active small molecules in concentrations ranging from 0.1 nM to 50 μM. Two enzymatic assays, along with molecular modeling, were then developed to confirm those targeting the virus 3CL protease and the RNA-dependent RNA polymerase. Several water extracts of herbal medicines were active in the cell-based assay and could be further developed as plant-derived anti–SARS-CoV-2 agents. Some of the active compounds identified in the screen were further tested in vivo, and it was found that mefloquine, nelfinavir, and extracts of Ganoderma lucidum (RF3), Perilla frutescens, and Mentha haplocalyx were effective in a challenge study using hamsters as disease model.Keywords
Funding Information
- Ministry of Science and Technology, Taiwan (MOST 108-3114-Y-001-002, MOST 109-0210-01-18-02)
- Academia Sinica (AS-SUMMIT-109, AS-KPQ-109-BioMed)
This publication has 61 references indexed in Scilit:
- Immunization of fucose-containing polysaccharides from Reishi mushroom induces antibodies to tumor-associated Globo H-series epitopesProceedings of the National Academy of Sciences of the United States of America, 2013
- Identification of myricetin and scutellarein as novel chemical inhibitors of the SARS coronavirus helicase, nsP13Bioorganic & Medicinal Chemistry Letters, 2012
- Ivermectin is a specific inhibitor of importin α/β-mediated nuclear import able to inhibit replication of HIV-1 and dengue virusBiochemical Journal, 2012
- Patchouli alcohol: in vitro direct anti-influenza virus sesquiterpene in Pogostemon cablin Benth.Journal of Natural Medicines, 2011
- Thiopurine analogues inhibit papain-like protease of severe acute respiratory syndrome coronavirusBiochemical Pharmacology, 2008
- Drug Insight: pharmacology and toxicity of thiopurine therapy in patients with IBDNature Clinical Practice Gastroenterology & Hepatology, 2007
- Structure‐Based Design and Synthesis of Highly Potent SARS‐CoV 3CL Protease InhibitorsChemBioChem, 2007
- In vitro susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compoundsJournal of Clinical Virology, 2004
- Small molecules targeting severe acute respiratory syndrome human coronavirusProceedings of the National Academy of Sciences of the United States of America, 2004
- HIV protease inhibitor nelfinavir inhibits replication of SARS-associated coronavirusBiochemical and Biophysical Research Communications, 2004