Loperamide Inhibits Replication of Severe Fever with Thrombocytopenia Syndrome Virus
Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease caused by the SFTS virus (SFTSV). SFTS is mainly prevalent in East Asia. It has a mortality rate of up to 30%, and there is no approved treatment against the disease. In this study, we evaluat...
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2021-05-01
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Online Access: | https://www.mdpi.com/1999-4915/13/5/869 |
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author | Shuzo Urata Jiro Yasuda Masaharu Iwasaki |
author_facet | Shuzo Urata Jiro Yasuda Masaharu Iwasaki |
author_sort | Shuzo Urata |
collection | DOAJ |
description | Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease caused by the SFTS virus (SFTSV). SFTS is mainly prevalent in East Asia. It has a mortality rate of up to 30%, and there is no approved treatment against the disease. In this study, we evaluated the effect of loperamide, an antidiarrheal and antihyperalgesic agent, on the propagation of SFTSV in a cell culture system. Methods: SFTSV-infected human cell lines were exposed to loperamide, and viral titers were evaluated. To clarify the mode of action of loperamide, several chemical compounds having shared targets with loperamide were used. Calcium imaging was also performed to understand whether loperamide treatment affected calcium influx. Results: Loperamide inhibited SFTSV propagation in several cell lines. It inhibited SFTSV in the post-entry step and restricted calcium influx into the cell. Furthermore, nifedipine, a calcium channel inhibitor, also blocked post-entry step of SFTSV infection. Conclusions: Loperamide inhibits SFTSV propagation mainly by restraining calcium influx into the cytoplasm. This indicates that loperamide, a Food and Drug Administration (FDA)-approved drug, has the potential for being used as a treatment option against SFTS. |
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id | doaj.art-06c1da712f7c4337af79c795ea3c3d3f |
institution | Directory Open Access Journal |
issn | 1999-4915 |
language | English |
last_indexed | 2024-03-10T11:35:14Z |
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spelling | doaj.art-06c1da712f7c4337af79c795ea3c3d3f2023-11-21T18:55:14ZengMDPI AGViruses1999-49152021-05-0113586910.3390/v13050869Loperamide Inhibits Replication of Severe Fever with Thrombocytopenia Syndrome VirusShuzo Urata0Jiro Yasuda1Masaharu Iwasaki2National Research Center for the Control and Prevention of Infectious Diseases (CCPID), Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, JapanNational Research Center for the Control and Prevention of Infectious Diseases (CCPID), Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, JapanLaboratory of Emerging Viral Diseases, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Osaka 565-0871, JapanBackground: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease caused by the SFTS virus (SFTSV). SFTS is mainly prevalent in East Asia. It has a mortality rate of up to 30%, and there is no approved treatment against the disease. In this study, we evaluated the effect of loperamide, an antidiarrheal and antihyperalgesic agent, on the propagation of SFTSV in a cell culture system. Methods: SFTSV-infected human cell lines were exposed to loperamide, and viral titers were evaluated. To clarify the mode of action of loperamide, several chemical compounds having shared targets with loperamide were used. Calcium imaging was also performed to understand whether loperamide treatment affected calcium influx. Results: Loperamide inhibited SFTSV propagation in several cell lines. It inhibited SFTSV in the post-entry step and restricted calcium influx into the cell. Furthermore, nifedipine, a calcium channel inhibitor, also blocked post-entry step of SFTSV infection. Conclusions: Loperamide inhibits SFTSV propagation mainly by restraining calcium influx into the cytoplasm. This indicates that loperamide, a Food and Drug Administration (FDA)-approved drug, has the potential for being used as a treatment option against SFTS.https://www.mdpi.com/1999-4915/13/5/869severe fever with thrombocytopenia syndrome virusantiviralloperamide |
spellingShingle | Shuzo Urata Jiro Yasuda Masaharu Iwasaki Loperamide Inhibits Replication of Severe Fever with Thrombocytopenia Syndrome Virus Viruses severe fever with thrombocytopenia syndrome virus antiviral loperamide |
title | Loperamide Inhibits Replication of Severe Fever with Thrombocytopenia Syndrome Virus |
title_full | Loperamide Inhibits Replication of Severe Fever with Thrombocytopenia Syndrome Virus |
title_fullStr | Loperamide Inhibits Replication of Severe Fever with Thrombocytopenia Syndrome Virus |
title_full_unstemmed | Loperamide Inhibits Replication of Severe Fever with Thrombocytopenia Syndrome Virus |
title_short | Loperamide Inhibits Replication of Severe Fever with Thrombocytopenia Syndrome Virus |
title_sort | loperamide inhibits replication of severe fever with thrombocytopenia syndrome virus |
topic | severe fever with thrombocytopenia syndrome virus antiviral loperamide |
url | https://www.mdpi.com/1999-4915/13/5/869 |
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