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

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 antivi...

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Bibliographic Details
Published in:Viruses 2023-02, Vol.15 (2), p.452
Main Authors: Nakajima, Shogo, Ohashi, Hirofumi, Akazawa, Daisuke, Torii, Shiho, Suzuki, Rigel, Fukuhara, Takasuke, Watashi, Koichi
Format: Article
Language:English
Subjects:
Antifungal agents
Antiviral activity
antiviral agent
Antiviral agents
Antiviral Agents - pharmacology
Brief Report
Caspofungin
Cell culture
Coronaviruses
COVID-19
Cytotoxicity
Dehydrogenases
Drug dosages
echinocandin
Echinocandins
Epithelial cells
FDA approval
Humans
Infections
Infectious diseases
Medical research
Medicine, Experimental
Micafungin
Micafungin - pharmacology
Pandemics
Replication
RNA Replication
RNA, Viral
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
Viral infections
Viruses
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Summary: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 (IC ) of 5.25 and 6.51 µM, respectively (3.8 to 4.7-fold stronger than micafungin) and 50% cytotoxic concentration (CC ) 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.
ISSN:1999-4915
1999-4915
DOI:10.3390/v15020452