Amodiaquine derivatives as inhibitors of severe fever with thrombocytopenia syndrome virus (SFTSV) replication
Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved..
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne viral infection caused by a bandavirus in the family of Phenuiviridae, commonly known as SFTS virus (SFTSV). We have previously isolated SFTSV from blood samples of SFTS patients and established an antiviral assay system to identify selective inhibitors of SFTSV in vitro. Using the assay system, the antimalarial agent amodiaquine was identified as a selective inhibitor of SFTSV replication. However, due to its insufficient antiviral activity, 98 amodiaquine derivatives were newly synthesized and examined for their anti-SFTSV activity. Among the derivatives, some compounds showed selective inhibitory effect on SFTSV replication in vitro. The 50% effective concentration (EC50) and cytotoxic concentration (CC50) of the most active compound (C-90) were 2.6 ± 0.6 and >50 μM, respectively. This EC50 value was comparable to or slightly better than that of favipiravir (4.1 ± 0.6 μM). On the other hand, pharmacokinetic studies in vivo revealed that C-90 was poor in its oral bioavailability in mice. Therefore, we further designed and synthesized derivatives and obtained 2 compounds with selective anti-SFTSV activity in vitro and improved pharmacokinetics in vivo.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:210 |
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| Enthalten in: |
Antiviral research - 210(2023) vom: 22. Feb., Seite 105479 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Baba, Masanori [VerfasserIn] |
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| Links: |
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| Themen: |
220236ED28 |
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| Anmerkungen: |
Date Completed 23.01.2023 Date Revised 16.02.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.antiviral.2022.105479 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM35077613X |
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| 520 | |a Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved. | ||
| 520 | |a Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne viral infection caused by a bandavirus in the family of Phenuiviridae, commonly known as SFTS virus (SFTSV). We have previously isolated SFTSV from blood samples of SFTS patients and established an antiviral assay system to identify selective inhibitors of SFTSV in vitro. Using the assay system, the antimalarial agent amodiaquine was identified as a selective inhibitor of SFTSV replication. However, due to its insufficient antiviral activity, 98 amodiaquine derivatives were newly synthesized and examined for their anti-SFTSV activity. Among the derivatives, some compounds showed selective inhibitory effect on SFTSV replication in vitro. The 50% effective concentration (EC50) and cytotoxic concentration (CC50) of the most active compound (C-90) were 2.6 ± 0.6 and >50 μM, respectively. This EC50 value was comparable to or slightly better than that of favipiravir (4.1 ± 0.6 μM). On the other hand, pharmacokinetic studies in vivo revealed that C-90 was poor in its oral bioavailability in mice. Therefore, we further designed and synthesized derivatives and obtained 2 compounds with selective anti-SFTSV activity in vitro and improved pharmacokinetics in vivo | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Amodiaquine derivatives | |
| 650 | 4 | |a Antiviral | |
| 650 | 4 | |a Favipiravir | |
| 650 | 4 | |a Replication | |
| 650 | 4 | |a SFTSV | |
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| 650 | 7 | |a Antiviral Agents |2 NLM | |
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| 700 | 1 | |a Toyama, Masaaki |e verfasserin |4 aut | |
| 700 | 1 | |a Sakakibara, Norikazu |e verfasserin |4 aut | |
| 700 | 1 | |a Shimojima, Masayuki |e verfasserin |4 aut | |
| 700 | 1 | |a Saijo, Masayuki |e verfasserin |4 aut | |
| 700 | 1 | |a Niwa, Takuro |e verfasserin |4 aut | |
| 700 | 1 | |a Yagi, Yoshiki |e verfasserin |4 aut | |
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