From the journal:

Chemical Communications

Design and concise synthesis of halicyclamine-inspired bis-macrocycles targeting DedA membrane proteins

Toshiaki Wayama, ORCID logo a   Riku Horinouchi,b   Masayoshi Arai,*c   Hirofumi Ohashi,d   Koichi Watashi,*d   Satoshi Yoshida,e   Sota Sato, ORCID logo †ef   Sachiko Tsukamoto ORCID logo g  and  Hiroki Oguri ORCID logo *a  

* Corresponding authors

a Department of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
E-mail: hirokioguri@g.ecc.u-tokyo.ac.jp

b School of Pharmaceutical Sciences, The University of Osaka, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan

c Graduate School and School of Pharmaceutical Sciences, The University of Osaka, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan
E-mail: araim@phs.osaka-u.ac.jp

d Department of Drug Development, National Institute of Infectious Diseases, Japan Institute for Health Security, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan
E-mail: watashi.k@jihs.go.jp

e Department of Applied Chemistry, School of Engineering, The University of Tokyo, FS CREATION, Mitsui LINK Lab, Kashiwanoha 1, 6-6-2 Kashiwanoha, Kashiwa, Chiba 277-0882, Japan

f Institute for Molecular Science, 5-1 Higashiyama, Myodaiji, Okazaki, Aichi 444-8787, Japan

g Department of Natural Medicines, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oehonmachi, Chuo-ku, Kumamoto 862-0973, Japan

Abstract

DedA membrane proteins promote the formation of double-membrane vesicles serving as replication platforms for RNA viruses, including SARS-CoV-2. Inspired by the only known inhibitor, halicyclamine A, we developed a concise biomimetic synthesis of halicyclamine-inspired macrocycles, identifying bis-macrocycles that suppress SARS-CoV-2 replication, while exhibiting DedA-associated activity in a bacterial overexpression assay.

Graphical abstract: Design and concise synthesis of halicyclamine-inspired bis-macrocycles targeting DedA membrane proteins

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Article information

DOI
https://doi.org/10.1039/D6CC01052K
Article type
Communication
Submitted
18 Feb 2026
Accepted
10 Apr 2026
First published
10 Apr 2026
This article is Open Access
Creative Commons BY-NC license

Chem. Commun., 2026, Advance Article

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Design and concise synthesis of halicyclamine-inspired bis-macrocycles targeting DedA membrane proteins

T. Wayama, R. Horinouchi, M. Arai, H. Ohashi, K. Watashi, S. Yoshida, S. Sato, S. Tsukamoto and H. Oguri, Chem. Commun., 2026, Advance Article , DOI: 10.1039/D6CC01052K

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