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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 \u00b5M, respectively (3.8 to 4.7-fold stronger than micafungin) and 50% cytotoxic concentration (CC50) of &gt;64 \u00b5M 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.<\/jats:p>","DOI":"10.3390\/v15020452","type":"journal-article","created":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T04:59:10Z","timestamp":1675659550000},"page":"452","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Antiviral Activity of Micafungin and Its Derivatives against SARS-CoV-2 RNA Replication"],"prefix":"10.3390","volume":"15","author":[{"given":"Shogo","family":"Nakajima","sequence":"first","affiliation":[{"name":"Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan"},{"name":"Department of Virology II, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan"},{"name":"Choju Medical Institute, Fukushimura Hospital, 19-14 Yamanaka, Noyoricho, Toyohashi-shi 441-8124, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirofumi","family":"Ohashi","sequence":"additional","affiliation":[{"name":"Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5205-6776","authenticated-orcid":false,"given":"Daisuke","family":"Akazawa","sequence":"additional","affiliation":[{"name":"Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiho","family":"Torii","sequence":"additional","affiliation":[{"name":"Laboratory of Virus Control, Research Institute for Microbial Diseases, Osaka University, Suita 565-0871, Japan"},{"name":"Insect-Virus Interactions Unit, Department of Virology, Institut Pasteur, 75015 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rigel","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Medicine, Hokkaido University, N-15, W-7, Kita-ku, Sapporo 060-8638, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5471-8331","authenticated-orcid":false,"given":"Takasuke","family":"Fukuhara","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Medicine, Hokkaido University, N-15, W-7, Kita-ku, Sapporo 060-8638, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koichi","family":"Watashi","sequence":"additional","affiliation":[{"name":"Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan"},{"name":"Department of Virology II, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan"},{"name":"Department of Applied Biological Sciences, Tokyo University of Science, 2641 Yamazaki, Noda 278-8510, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1021\/acs.jmedchem.6b01594","article-title":"Discovery and Synthesis of a Phosphoramidate Prodrug of a Pyrrolo[2,1-f][triazin-4-amino] Adenine C-Nucleoside (GS-5734) for the Treatment of Ebola and Emerging Viruses","volume":"60","author":"Siegel","year":"2017","journal-title":"J. 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