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Potential anti-COVID-19 agents, cepharanthine and nelfinavir, and their usage for combination treatment.
Ohashi, Hirofumi; Watashi, Koichi; Saso, Wakana; Shionoya, Kaho; Iwanami, Shoya; Hirokawa, Takatsugu; Shirai, Tsuyoshi; Kanaya, Shigehiko; Ito, Yusuke; Kim, Kwang Su; Nomura, Takao; Suzuki, Tateki; Nishioka, Kazane; Ando, Shuji; Ejima, Keisuke; Koizumi, Yoshiki; Tanaka, Tomohiro; Aoki, Shin; Kuramochi, Kouji; Suzuki, Tadaki; Hashiguchi, Takao; Maenaka, Katsumi; Matano, Tetsuro; Muramatsu, Masamichi; Saijo, Masayuki; Aihara, Kazuyuki; Iwami, Shingo; Takeda, Makoto; McKeating, Jane A; Wakita, Takaji.
  • Ohashi H; Department of Virology II, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
  • Watashi K; Department of Applied Biological Science, Tokyo University of Science, Noda 278-8510, Japan.
  • Saso W; Department of Virology II, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
  • Shionoya K; Department of Applied Biological Science, Tokyo University of Science, Noda 278-8510, Japan.
  • Iwanami S; Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
  • Hirokawa T; MIRAI, JST, Saitama 332-0012, Japan.
  • Shirai T; Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
  • Kanaya S; Department of Virology II, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
  • Ito Y; The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
  • Kim KS; AIDS Research Center, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
  • Nomura T; Department of Virology II, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
  • Suzuki T; Department of Applied Biological Science, Tokyo University of Science, Noda 278-8510, Japan.
  • Nishioka K; Department of Biology, Faculty of Sciences, Kyushu University, Fukuoka 812-8581, Japan.
  • Ando S; Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology, Tokyo 135-0064, Japan.
  • Ejima K; Division of Biomedical Science, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan.
  • Koizumi Y; Transborder Medical Research Center, University of Tsukuba, Tsukuba 305-8575, Japan.
  • Tanaka T; Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, Nagahama 526-0829, Japan.
  • Aoki S; Graduate School of Science and Technology, Nara Institute of Science and Technology, Ikoma 630-0192, Japan.
  • Kuramochi K; Department of Biology, Faculty of Sciences, Kyushu University, Fukuoka 812-8581, Japan.
  • Suzuki T; Department of Biology, Faculty of Sciences, Kyushu University, Fukuoka 812-8581, Japan.
  • Hashiguchi T; Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
  • Maenaka K; Department of Virology, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan.
  • Matano T; Department of Virology II, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
  • Muramatsu M; Department of Applied Biological Science, Tokyo University of Science, Noda 278-8510, Japan.
  • Saijo M; Department of Virology I, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
  • Aihara K; Department of Epidemiology and Biostatistics, Indiana University School of Public Health-Bloomington, Bloomington, IN 47405, USA.
  • Iwami S; National Center for Global Health and Medicine, Tokyo 162-8655, Japan.
  • Takeda M; Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda 278-8510, Japan.
  • McKeating JA; Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda 278-8510, Japan.
  • Wakita T; Research Institute for Science and Technology, Tokyo University of Science, Noda 278-8510, Japan.
iScience ; 24(4): 102367, 2021 Apr 23.
Article in English | MEDLINE | ID: covidwho-1157438
Semantic information from SemMedBD (by NLM)
1. Therapeutic procedure TREATS COVID-19
Subject
Therapeutic procedure
Predicate
TREATS
Object
COVID-19
2. Cell Count USES TMPRSS2 gene|TMPRSS2
Subject
Cell Count
Predicate
USES
Object
TMPRSS2 gene|TMPRSS2
3. nelfinavir DISRUPTS Virus Replication
Subject
nelfinavir
Predicate
DISRUPTS
Object
Virus Replication
4. cepharanthine INHIBITS Peptide Hydrolases
Subject
cepharanthine
Predicate
INHIBITS
Object
Peptide Hydrolases
5. Therapeutic procedure TREATS COVID-19
Subject
Therapeutic procedure
Predicate
TREATS
Object
COVID-19
6. Cell Count USES TMPRSS2 gene|TMPRSS2
Subject
Cell Count
Predicate
USES
Object
TMPRSS2 gene|TMPRSS2
7. nelfinavir DISRUPTS Virus Replication
Subject
nelfinavir
Predicate
DISRUPTS
Object
Virus Replication
8. cepharanthine INHIBITS Peptide Hydrolases
Subject
cepharanthine
Predicate
INHIBITS
Object
Peptide Hydrolases
ABSTRACT
Antiviral treatments targeting the coronavirus disease 2019 are urgently required. We screened a panel of already approved drugs in a cell culture model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and identified two new agents having higher antiviral potentials than the drug candidates such as remdesivir and chroloquine in VeroE6/TMPRSS2 cells the anti-inflammatory drug cepharanthine and human immunodeficiency virus protease inhibitor nelfinavir. Cepharanthine inhibited SARS-CoV-2 entry through the blocking of viral binding to target cells, while nelfinavir suppressed viral replication partly by protease inhibition. Consistent with their different modes of action, synergistic effect of this combined treatment to limit SARS-CoV-2 proliferation was highlighted. Mathematical modeling in vitro antiviral activity coupled with the calculated total drug concentrations in the lung predicts that nelfinavir will shorten the period until viral clearance by 4.9 days and the combining cepharanthine/nelfinavir enhanced their predicted efficacy. These results warrant further evaluation of the potential anti-SARS-CoV-2 activity of cepharanthine and nelfinavir.
Keywords

Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Language: English Journal: IScience Year: 2021 Document Type: Article Affiliation country: J.isci.2021.102367

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Language: English Journal: IScience Year: 2021 Document Type: Article Affiliation country: J.isci.2021.102367