Identification of existing pharmaceuticals and herbal medicines as inhibitors of SARS-CoV-2 infection
Journal
Proceedings of the National Academy of Sciences of the United States of America
Journal Volume
118
Journal Issue
5
Date Issued
2021-02-02
Author(s)
Jan, Jia Tsrong
Cheng, Ting Jen Rachel
Ma, Hsiu Hua
Wu, Ying Ta
Yang, Wen Bin
Cheng, Cheng Wei
Chen, Xiaorui
Chou, Ting Hung
Shie, Jiun Jie
Cheng, Wei Chieh
Chein, Rong Jie
Mao, Shi Shan
Ma, Che
Hung, Shang Cheng
Wong, Chi Huey
Abstract
© 2021 National Academy of Sciences. All rights reserved. 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.
Subjects
Animal studies | Antiviral | Cell-based | Drug repurposing | SARS-CoV-2
Animal studies; Antiviral; Cell-based; Drug repurposing; SARS-CoV-2
SDGs
Other Subjects
amprenavir; atazanavir; azelnidipine; boceprevir; cepharanthine; daclatasvir; danoprevir; darunavir; dronedarone; emetine; herbaceous agent; hydroxychloroquine; indinavir; ivacaftor; ivermectin; lopinavir; maduramicin; mefloquine; monensin; moxidectin; nelfinavir; penfluridol; remdesivir; ritonavir; salinomycin; saquinavir; telaprevir; tioguanine; antivirus agent; plant extract; adult; amino acid sequence; animal cell; animal experiment; animal model; antiviral activity; Article; controlled study; coronavirus disease 2019; drug efficacy; drug safety; enzyme assay; exocytosis; Ganoderma lucidum; glycosylation; herbal medicine; human; human tissue; in vitro study; in vivo study; male; Mentha; Mentha haplocalyx; molecular model; nonhuman; Perilla frutescens; priority journal; protein degradation; protein protein interaction; RNA replication; animal; chemistry; Chlorocebus aethiops; disease model; drug effect; drug repositioning; drug therapy; epidemiology; female; genetics; hamster; pandemic; procedures; Vero cell line; virology; Adult; Animals; Antiviral Agents; Chlorocebus aethiops; COVID-19; Cricetinae; Disease Models, Animal; Drug Repositioning; Female; Humans; Male; Pandemics; Plant Extracts; SARS-CoV-2; Vero Cells
Type
journal article