Antiviral activity of ciclesonide acetal derivatives blocking SARS-CoV-2 RNA replication

Genichiro Tsuji; Shogo Nakajima; Koichi Watashi; Shiho Torii; Rigel Suzuki; Takasuke Fukuhara; Nobumichi Ohoka; Takao Inoue; Yosuke Demizu

Journal of Pharmacological Sciences (Jul 2022)

Antiviral activity of ciclesonide acetal derivatives blocking SARS-CoV-2 RNA replication

Genichiro Tsuji,
Shogo Nakajima,
Koichi Watashi,
Shiho Torii,
Rigel Suzuki,
Takasuke Fukuhara,
Nobumichi Ohoka,
Takao Inoue,
Yosuke Demizu

Affiliations

Genichiro Tsuji: Division of Organic Chemistry, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, 210-9501, Japan; Corresponding author. Fax: +81 44 270 6578.
Shogo Nakajima: National Institute of Infectious Diseases, Research Center for Drug and Vaccine Development, 1-23-1 Toyama, Shinjuku-ku, Tokyo, 162-8640, Japan; National Institute of Infectious Diseases, Department of Virology II, 1-23-1 Toyama, Shinjuku-ku, Tokyo, 162-8640, Japan; Choju Medical Institute, 19-14 Yamanaka, Noyoricho, Toyohashi, Aichi, 441-8124, Japan
Koichi Watashi: National Institute of Infectious Diseases, Research Center for Drug and Vaccine Development, 1-23-1 Toyama, Shinjuku-ku, Tokyo, 162-8640, Japan; National Institute of Infectious Diseases, Department of Virology II, 1-23-1 Toyama, Shinjuku-ku, Tokyo, 162-8640, Japan; Department of Applied Biological Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, 278-8510, Japan
Shiho Torii: Laboratory of Virus Control, Research Institute for Microbial Diseases, Osaka University, Suita, 565-0871, Japan; Insect-Virus Interactions Unit, Department of Virology, Institute Pasteur, Paris, 75015, France
Rigel Suzuki: Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, N-15, W-7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
Takasuke Fukuhara: Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, N-15, W-7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
Nobumichi Ohoka: Division of Molecular Target and Gene Therapy Products, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, 210-9501, Japan
Takao Inoue: Division of Molecular Target and Gene Therapy Products, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, 210-9501, Japan
Yosuke Demizu: Division of Organic Chemistry, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, 210-9501, Japan; Graduate School of Medical Life Science, Yokohama City University, 1-7-29, Yokohama, Kanagawa, 230-0045, Japan; Corresponding author. Division of Organic Chemistry, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, 210-9501, Japan. Fax: +81 44 270 6578.

Journal volume & issue: Vol. 149, no. 3
pp. 81 – 84

Abstract

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Ciclesonide (Cic) is approved as an inhalant for asthma and was clinically tested as a candidate therapy for coronavirus disease 2019 (COVID-19). Its active metabolite Cic2 was recently reported to suppress genomic RNA replication of severe acute respiratory syndrome coronavirus 2. In this study, we designed and synthesized a set of ciclesonide-acetal (Cic-acetal) derivatives. Among designated compounds, some Cic-acetal derivatives with a linear alkyl chain exhibited strong viral copy-number reduction activities compared with Cic2. These compounds might serve as lead compounds for developing novel anti-COVID-19 agents.

Published in Journal of Pharmacological Sciences

ISSN: 1347-8613 (Print)
Publisher: Elsevier
Country of publisher: Japan
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: http://www.journals.elsevier.com/journal-of-pharmacological-sciences

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