Antiviral Activity of Micafungin and Its Derivatives against SARS-CoV-2 RNA Replication

Shogo Nakajima; Hirofumi Ohashi; Daisuke Akazawa; Shiho Torii; Rigel Suzuki; Takasuke Fukuhara; Koichi Watashi

doi:10.3390/v15020452

Antiviral Activity of Micafungin and Its Derivatives against SARS-CoV-2 RNA Replication

Viruses. 2023 Feb 6;15(2):452. doi: 10.3390/v15020452.

Authors

Shogo Nakajima^{1

2

3}, Hirofumi Ohashi¹, Daisuke Akazawa¹, Shiho Torii^{4

5}, Rigel Suzuki⁶, Takasuke Fukuhara⁶, Koichi Watashi^{1

2

7}

Affiliations

¹ Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
² Department of Virology II, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
³ Choju Medical Institute, Fukushimura Hospital, 19-14 Yamanaka, Noyoricho, Toyohashi-shi 441-8124, Japan.
⁴ Laboratory of Virus Control, Research Institute for Microbial Diseases, Osaka University, Suita 565-0871, Japan.
⁵ Insect-Virus Interactions Unit, Department of Virology, Institut Pasteur, 75015 Paris, France.
⁶ Department of Microbiology and Immunology, Faculty of Medicine, Hokkaido University, N-15, W-7, Kita-ku, Sapporo 060-8638, Japan.
⁷ Department of Applied Biological Sciences, Tokyo University of Science, 2641 Yamazaki, Noda 278-8510, Japan.

Abstract

Echinocandin antifungal drugs, including micafungin, anidulafungin, and caspofungin, have been recently reported to exhibit antiviral effects against various viruses such as flavivirus, alphavirus, and coronavirus. In this study, we focused on micafungin and its derivatives and analyzed their antiviral activities against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The micafungin derivatives Mi-2 and Mi-5 showed higher antiviral activity than micafungin, with 50% maximal inhibitory concentration (IC₅₀) of 5.25 and 6.51 µM, respectively (3.8 to 4.7-fold stronger than micafungin) and 50% cytotoxic concentration (CC₅₀) of >64 µM in VeroE6/TMPRSS2 cells. This high anti-SARS-CoV-2 activity was also conserved in human lung epithelial cell-derived Calu-3 cells. Micafungin, Mi-2, and Mi-5 were suggested to inhibit the intracellular virus replication process; additionally, these compounds were active against SARS-CoV-2 variants, including Delta (AY.122, hCoV-19/Japan/TY11-927/2021), Omicron (BA.1.18, hCoV-19/Japan/TY38-873/2021), a variant resistant to remdesivir (R10/E796G C799F), and a variant resistant to casirivimab/imdevimab antibody cocktail (E406W); thus, our results provide basic evidence for the potential use of micafungin derivatives for developing antiviral agents.

Keywords: antiviral agent; echinocandin; micafungin; replication; severe acute respiratory syndrome coronavirus 2.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antiviral Agents* / pharmacology
COVID-19*
Humans
Micafungin / pharmacology
RNA Replication
RNA, Viral
SARS-CoV-2

Substances

Antiviral Agents
Micafungin
RNA, Viral

Supplementary concepts

SARS-CoV-2 variants

Grants and funding

This work was supported by the Agency for Medical Research and Development (AMED) (JP21fk0108589, JP22fk0310504, JP22jm0210068, and JP22wm0325007), the Japan Society for the Promotion of Science KAKENHI (JP20H03499, JP20K16267, and JP21H02449), JST MIRAI program (JPMJMI22G1), and the Takeda Science Foundation.