Inhibition of furin-like enzymatic activities and SARS-CoV-2 infection by osthole and phenolic compounds with aryl side chains
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), spread as a pandemic and caused damage to people’s lives and countries’ economies. The spike (S) protein of SARS-CoV-2 contains a cleavage motif, Arg-X-X-Arg, for furin and furin-like enzymes...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223017389 |
| _version_ | 1797404607196954624 |
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| author | Yuka Kiba Takashi Tanikawa Tsuyoshi Hayashi Hitoshi Kamauchi Taishi Seki Ryuichiro Suzuki Masashi Kitamura |
| author_facet | Yuka Kiba Takashi Tanikawa Tsuyoshi Hayashi Hitoshi Kamauchi Taishi Seki Ryuichiro Suzuki Masashi Kitamura |
| author_sort | Yuka Kiba |
| collection | DOAJ |
| description | Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), spread as a pandemic and caused damage to people’s lives and countries’ economies. The spike (S) protein of SARS-CoV-2 contains a cleavage motif, Arg-X-X-Arg, for furin and furin-like enzymes at the boundary of the S1/S2 subunits. Given that cleavage plays a crucial role in S protein activation and viral entry, the cleavage motif was selected as the target. Our previous fluorogenic substrate study showed that osthole, a coumarin compound, inhibits furin-like enzyme activity. In this study, we examined the potential activities of 15 compounds with a structure-activity relationship with osthole, and evaluated their protective ability against SARS-CoV-2 infection. Of the 15 compounds tested, compounds C1 and C2 exhibited the inhibitory effects of osthole against furin-like enzymatic activity; however, little or no inhibitory effects against furin activity were observed. We further examined the inhibition of SARS-CoV-2 activity by compounds C1 and C2 using a Vero E6 cell line that expresses the transmembrane protease serine 2 (TMPRSS2). Compounds C1, C2, and osthole effectively inhibited SARS-CoV-2 infection. Therefore, osthole and its derivatives can potentially be used as therapeutic agents against SARS-CoV-2. |
| first_indexed | 2024-03-09T02:57:28Z |
| format | Article |
| id | doaj.art-d6bc43699e844feaa4efbd4b38b07b89 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-09T02:57:28Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-d6bc43699e844feaa4efbd4b38b07b892023-12-05T04:14:51ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-12-01169115940Inhibition of furin-like enzymatic activities and SARS-CoV-2 infection by osthole and phenolic compounds with aryl side chainsYuka Kiba0Takashi Tanikawa1Tsuyoshi Hayashi2Hitoshi Kamauchi3Taishi Seki4Ryuichiro Suzuki5Masashi Kitamura6School of Pharmacy, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University; 1–1, Keyakidai, Sakado, Saitama 350–0295, JapanSchool of Pharmacy, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University; 1–1, Keyakidai, Sakado, Saitama 350–0295, Japan; Corresponding authors.Department of Virology II, National Institute of Infectious Diseases, Tokyo, JapanDepartment of Pharmaceutical Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado City, Saitama 350-0295, JapanSchool of Pharmacy, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University; 1–1, Keyakidai, Sakado, Saitama 350–0295, JapanDepartment of Pharmaceutical Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado City, Saitama 350-0295, JapanSchool of Pharmacy, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University; 1–1, Keyakidai, Sakado, Saitama 350–0295, Japan; Corresponding authors.Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), spread as a pandemic and caused damage to people’s lives and countries’ economies. The spike (S) protein of SARS-CoV-2 contains a cleavage motif, Arg-X-X-Arg, for furin and furin-like enzymes at the boundary of the S1/S2 subunits. Given that cleavage plays a crucial role in S protein activation and viral entry, the cleavage motif was selected as the target. Our previous fluorogenic substrate study showed that osthole, a coumarin compound, inhibits furin-like enzyme activity. In this study, we examined the potential activities of 15 compounds with a structure-activity relationship with osthole, and evaluated their protective ability against SARS-CoV-2 infection. Of the 15 compounds tested, compounds C1 and C2 exhibited the inhibitory effects of osthole against furin-like enzymatic activity; however, little or no inhibitory effects against furin activity were observed. We further examined the inhibition of SARS-CoV-2 activity by compounds C1 and C2 using a Vero E6 cell line that expresses the transmembrane protease serine 2 (TMPRSS2). Compounds C1, C2, and osthole effectively inhibited SARS-CoV-2 infection. Therefore, osthole and its derivatives can potentially be used as therapeutic agents against SARS-CoV-2.http://www.sciencedirect.com/science/article/pii/S0753332223017389FurinSARS-CoV-2OstholeCoumarin |
| spellingShingle | Yuka Kiba Takashi Tanikawa Tsuyoshi Hayashi Hitoshi Kamauchi Taishi Seki Ryuichiro Suzuki Masashi Kitamura Inhibition of furin-like enzymatic activities and SARS-CoV-2 infection by osthole and phenolic compounds with aryl side chains Biomedicine & Pharmacotherapy Furin SARS-CoV-2 Osthole Coumarin |
| title | Inhibition of furin-like enzymatic activities and SARS-CoV-2 infection by osthole and phenolic compounds with aryl side chains |
| title_full | Inhibition of furin-like enzymatic activities and SARS-CoV-2 infection by osthole and phenolic compounds with aryl side chains |
| title_fullStr | Inhibition of furin-like enzymatic activities and SARS-CoV-2 infection by osthole and phenolic compounds with aryl side chains |
| title_full_unstemmed | Inhibition of furin-like enzymatic activities and SARS-CoV-2 infection by osthole and phenolic compounds with aryl side chains |
| title_short | Inhibition of furin-like enzymatic activities and SARS-CoV-2 infection by osthole and phenolic compounds with aryl side chains |
| title_sort | inhibition of furin like enzymatic activities and sars cov 2 infection by osthole and phenolic compounds with aryl side chains |
| topic | Furin SARS-CoV-2 Osthole Coumarin |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223017389 |
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