Inhibitory effect of doxycycline against dengue virus replication in vitro
Doxycycline is an antibiotic derived from tetracycline that possesses antimicrobial and anti-inflammatory activities. Antiviral activity of doxycycline against dengue virus has been reported previously; however, its anti-dengue properties need further investigation. This study was conducted to deter...
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| Veröffentlicht in: | Archives of virology 2014-04, Vol.159 (4), p.711-718 |
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| creator | Rothan, Hussin A Mohamed, Zulqarnain Paydar, Mohammadjavad Rahman, Noorsaadah Abd Yusof, Rohana |
| description | Doxycycline is an antibiotic derived from tetracycline that possesses antimicrobial and anti-inflammatory activities. Antiviral activity of doxycycline against dengue virus has been reported previously; however, its anti-dengue properties need further investigation. This study was conducted to determine the potential activity of doxycycline against dengue virus replication in vitro. Doxycycline inhibited the dengue virus serine protease (DENV2 NS2B-NS3pro) with an IC₅₀ value of 52.3 ± 6.2 μM at 37 °C (normal human temperature) and 26.7 ± 5.3 μM at 40 °C (high fever temperature). The antiviral activity of doxycycline was first tested at different concentrations against DENV2 using a plaque-formation assay. The virus titter decreased significantly after applying doxycycline at levels lower than its 50 % cytotoxic concentration (CC₅₀, 100 μM), showing concentration-dependent inhibition with a 50 % effective concentration (EC₅₀) of approximately 50 μM. Doxycycline significantly inhibited viral entry and post-infection replication of the four dengue serotypes, with serotype-specific inhibition (high activity against DENV2 and DENV4 compared to DENV1 and DENV3). Collectively, these findings underline the need for further experimental and clinical studies on doxycycline, utilizing its anti-dengue and anti-inflammatory activities to attenuate the clinical symptoms of dengue virus infection. |
| doi_str_mv | 10.1007/s00705-013-1880-7 |
| format | Article |
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Antiviral activity of doxycycline against dengue virus has been reported previously; however, its anti-dengue properties need further investigation. This study was conducted to determine the potential activity of doxycycline against dengue virus replication in vitro. Doxycycline inhibited the dengue virus serine protease (DENV2 NS2B-NS3pro) with an IC₅₀ value of 52.3 ± 6.2 μM at 37 °C (normal human temperature) and 26.7 ± 5.3 μM at 40 °C (high fever temperature). The antiviral activity of doxycycline was first tested at different concentrations against DENV2 using a plaque-formation assay. The virus titter decreased significantly after applying doxycycline at levels lower than its 50 % cytotoxic concentration (CC₅₀, 100 μM), showing concentration-dependent inhibition with a 50 % effective concentration (EC₅₀) of approximately 50 μM. Doxycycline significantly inhibited viral entry and post-infection replication of the four dengue serotypes, with serotype-specific inhibition (high activity against DENV2 and DENV4 compared to DENV1 and DENV3). Collectively, these findings underline the need for further experimental and clinical studies on doxycycline, utilizing its anti-dengue and anti-inflammatory activities to attenuate the clinical symptoms of dengue virus infection.</description><identifier>ISSN: 0304-8608</identifier><identifier>EISSN: 1432-8798</identifier><identifier>DOI: 10.1007/s00705-013-1880-7</identifier><identifier>PMID: 24142271</identifier><language>eng</language><publisher>Vienna: Springer-Verlag</publisher><subject>Amino acids ; anti-inflammatory activity ; Antiviral Agents - pharmacology ; antiviral properties ; Biomedical and Life Sciences ; Biomedicine ; clinical trials ; dengue ; Dengue fever ; Dengue virus ; Dengue Virus - drug effects ; Dengue Virus - physiology ; doxycycline ; Doxycycline - pharmacology ; Encephalitis ; fever ; Humans ; Infections ; Infectious Diseases ; Inhibitory Concentration 50 ; Medical Microbiology ; Original Article ; Peptides ; serine proteinases ; serotypes ; tetracycline ; Tropical diseases ; Viral Nonstructural Proteins - antagonists & inhibitors ; Viral Plaque Assay ; Virology ; Virus Internalization - drug effects ; virus replication ; Virus Replication - drug effects ; viruses ; West Nile virus</subject><ispartof>Archives of virology, 2014-04, Vol.159 (4), p.711-718</ispartof><rights>Springer-Verlag Wien 2013</rights><rights>Springer-Verlag Wien 2014</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c429t-a642b7bce409fdb66ac9fd81ddd79f75da53e7cb85b1b3af13d8c9e05aa5cf2b3</citedby><cites>FETCH-LOGICAL-c429t-a642b7bce409fdb66ac9fd81ddd79f75da53e7cb85b1b3af13d8c9e05aa5cf2b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00705-013-1880-7$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00705-013-1880-7$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24142271$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rothan, Hussin A</creatorcontrib><creatorcontrib>Mohamed, Zulqarnain</creatorcontrib><creatorcontrib>Paydar, Mohammadjavad</creatorcontrib><creatorcontrib>Rahman, Noorsaadah Abd</creatorcontrib><creatorcontrib>Yusof, Rohana</creatorcontrib><title>Inhibitory effect of doxycycline against dengue virus replication in vitro</title><title>Archives of virology</title><addtitle>Arch Virol</addtitle><addtitle>Arch Virol</addtitle><description>Doxycycline is an antibiotic derived from tetracycline that possesses antimicrobial and anti-inflammatory activities. Antiviral activity of doxycycline against dengue virus has been reported previously; however, its anti-dengue properties need further investigation. This study was conducted to determine the potential activity of doxycycline against dengue virus replication in vitro. Doxycycline inhibited the dengue virus serine protease (DENV2 NS2B-NS3pro) with an IC₅₀ value of 52.3 ± 6.2 μM at 37 °C (normal human temperature) and 26.7 ± 5.3 μM at 40 °C (high fever temperature). The antiviral activity of doxycycline was first tested at different concentrations against DENV2 using a plaque-formation assay. The virus titter decreased significantly after applying doxycycline at levels lower than its 50 % cytotoxic concentration (CC₅₀, 100 μM), showing concentration-dependent inhibition with a 50 % effective concentration (EC₅₀) of approximately 50 μM. Doxycycline significantly inhibited viral entry and post-infection replication of the four dengue serotypes, with serotype-specific inhibition (high activity against DENV2 and DENV4 compared to DENV1 and DENV3). Collectively, these findings underline the need for further experimental and clinical studies on doxycycline, utilizing its anti-dengue and anti-inflammatory activities to attenuate the clinical symptoms of dengue virus infection.</description><subject>Amino acids</subject><subject>anti-inflammatory activity</subject><subject>Antiviral Agents - pharmacology</subject><subject>antiviral properties</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>clinical trials</subject><subject>dengue</subject><subject>Dengue fever</subject><subject>Dengue virus</subject><subject>Dengue Virus - drug effects</subject><subject>Dengue Virus - physiology</subject><subject>doxycycline</subject><subject>Doxycycline - pharmacology</subject><subject>Encephalitis</subject><subject>fever</subject><subject>Humans</subject><subject>Infections</subject><subject>Infectious Diseases</subject><subject>Inhibitory Concentration 50</subject><subject>Medical Microbiology</subject><subject>Original Article</subject><subject>Peptides</subject><subject>serine proteinases</subject><subject>serotypes</subject><subject>tetracycline</subject><subject>Tropical diseases</subject><subject>Viral Nonstructural Proteins - antagonists & inhibitors</subject><subject>Viral Plaque Assay</subject><subject>Virology</subject><subject>Virus Internalization - drug effects</subject><subject>virus replication</subject><subject>Virus Replication - drug effects</subject><subject>viruses</subject><subject>West Nile virus</subject><issn>0304-8608</issn><issn>1432-8798</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqNkctuFDEQRS1ERIbAB7CBltiw6eDyo-1eoohHUCQWkLXl5-Coxx7s7oj5ezx0QIhFlE2VVHXqWtZB6AXgc8BYvK2tYN5joD1IiXvxCG2AUdJLMcrHaIMpZr0csDxFT2u9wbgNKH-CTgkDRoiADfp8mb5HE-dcDp0Pwdu5y6Fz-efBHuwUk-_0VsdU5875tF18dxvLUrvi91O0eo45dTG14VzyM3QS9FT987t-hq4_vP928am_-vLx8uLdVW8ZGedeD4wYYaxneAzODIO2rUtwzokxCO40p15YI7kBQ3UA6qQdPeZacxuIoWfozZq7L_nH4uusdrFaP006-bxUBRwGwQllw0NQkAQwEQ19_R96k5eS2kd-U1jiUUKjYKVsybUWH9S-xJ0uBwVYHZ2o1YlqTtTRiTomv7xLXszOu78XfyQ0gKxAbau09eWfp-9JfbUeBZ2V3pZY1fVXgoE1ywMbYaC_ANfvoDw</recordid><startdate>20140401</startdate><enddate>20140401</enddate><creator>Rothan, Hussin A</creator><creator>Mohamed, Zulqarnain</creator><creator>Paydar, Mohammadjavad</creator><creator>Rahman, Noorsaadah Abd</creator><creator>Yusof, Rohana</creator><general>Springer-Verlag</general><general>Springer Vienna</general><general>Springer Nature B.V</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><scope>7T2</scope><scope>7U2</scope><scope>C1K</scope><scope>F1W</scope><scope>H95</scope><scope>H97</scope><scope>L.G</scope></search><sort><creationdate>20140401</creationdate><title>Inhibitory effect of doxycycline against dengue virus replication in vitro</title><author>Rothan, Hussin A ; Mohamed, Zulqarnain ; Paydar, Mohammadjavad ; Rahman, Noorsaadah Abd ; Yusof, Rohana</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c429t-a642b7bce409fdb66ac9fd81ddd79f75da53e7cb85b1b3af13d8c9e05aa5cf2b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Amino acids</topic><topic>anti-inflammatory activity</topic><topic>Antiviral Agents - 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Antiviral activity of doxycycline against dengue virus has been reported previously; however, its anti-dengue properties need further investigation. This study was conducted to determine the potential activity of doxycycline against dengue virus replication in vitro. Doxycycline inhibited the dengue virus serine protease (DENV2 NS2B-NS3pro) with an IC₅₀ value of 52.3 ± 6.2 μM at 37 °C (normal human temperature) and 26.7 ± 5.3 μM at 40 °C (high fever temperature). The antiviral activity of doxycycline was first tested at different concentrations against DENV2 using a plaque-formation assay. The virus titter decreased significantly after applying doxycycline at levels lower than its 50 % cytotoxic concentration (CC₅₀, 100 μM), showing concentration-dependent inhibition with a 50 % effective concentration (EC₅₀) of approximately 50 μM. Doxycycline significantly inhibited viral entry and post-infection replication of the four dengue serotypes, with serotype-specific inhibition (high activity against DENV2 and DENV4 compared to DENV1 and DENV3). Collectively, these findings underline the need for further experimental and clinical studies on doxycycline, utilizing its anti-dengue and anti-inflammatory activities to attenuate the clinical symptoms of dengue virus infection.</abstract><cop>Vienna</cop><pub>Springer-Verlag</pub><pmid>24142271</pmid><doi>10.1007/s00705-013-1880-7</doi><tpages>8</tpages></addata></record> |
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| subjects | Amino acids anti-inflammatory activity Antiviral Agents - pharmacology antiviral properties Biomedical and Life Sciences Biomedicine clinical trials dengue Dengue fever Dengue virus Dengue Virus - drug effects Dengue Virus - physiology doxycycline Doxycycline - pharmacology Encephalitis fever Humans Infections Infectious Diseases Inhibitory Concentration 50 Medical Microbiology Original Article Peptides serine proteinases serotypes tetracycline Tropical diseases Viral Nonstructural Proteins - antagonists & inhibitors Viral Plaque Assay Virology Virus Internalization - drug effects virus replication Virus Replication - drug effects viruses West Nile virus |
| title | Inhibitory effect of doxycycline against dengue virus replication in vitro |
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