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

doi:10.1016/j.jphs.2022.04.001

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

J Pharmacol Sci. 2022 Jul;149(3):81-84. doi: 10.1016/j.jphs.2022.04.001. Epub 2022 Apr 18.

Authors

Genichiro Tsuji¹, Shogo Nakajima², Koichi Watashi³, Shiho Torii⁴, Rigel Suzuki⁵, Takasuke Fukuhara⁵, Nobumichi Ohoka⁶, Takao Inoue⁶, Yosuke Demizu⁷

Affiliations

¹ Division of Organic Chemistry, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, 210-9501, Japan. Electronic address: gtsuji@nihs.go.jp.
² 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.
³ 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.
⁴ 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.
⁵ Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, N-15, W-7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
⁶ Division of Molecular Target and Gene Therapy Products, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa, 210-9501, Japan.
⁷ 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. Electronic address: demizu@nihs.go.jp.

Abstract

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.

Keywords: Antiviral activity; Ciclesonide; SARS-CoV2.

MeSH terms

Acetals / pharmacology
Antiviral Agents* / pharmacology
COVID-19 Drug Treatment*
Humans
Pregnenediones
RNA, Viral / genetics
RNA, Viral / pharmacology
SARS-CoV-2
Virus Replication / genetics

Substances

Acetals
Antiviral Agents
Pregnenediones
RNA, Viral
ciclesonide