A combination of doxycycline and ribavirin alleviated chikungunya infection
Lack of vaccine and effective antiviral drugs against chikungunya virus (CHIKV) outbreaks have led to significant impact on health care in the developing world. Here, we evaluated the antiviral effects of tetracycline (TETRA) derivatives and other common antiviral agents against CHIKV. Our results s...
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| creator | Rothan, Hussin A Bahrani, Hirbod Mohamed, Zulqarnain Teoh, Teow Chong Shankar, Esaki M Rahman, Noorsaadah A Yusof, Rohana |
| description | Lack of vaccine and effective antiviral drugs against chikungunya virus (CHIKV) outbreaks have led to significant impact on health care in the developing world. Here, we evaluated the antiviral effects of tetracycline (TETRA) derivatives and other common antiviral agents against CHIKV. Our results showed that within the TETRA derivatives group, Doxycycline (DOXY) exhibited the highest inhibitory effect against CHIKV replication in Vero cells. On the other hand, in the antiviral group Ribavirin (RIBA) showed higher inhibitory effects against CHIKV replication compared to Aciclovir (ACIC). Interestingly, RIBA inhibitory effects were also higher than all but DOXY within the TETRA derivatives group. Docking studies of DOXY to viral cysteine protease and E2 envelope protein showed non-competitive interaction with docking energy of -6.6±0.1 and -6.4±0.1 kcal/mol respectively. The 50% effective concentration (EC50) of DOXY and RIBA was determined to be 10.95±2.12 μM and 15.51±1.62 μM respectively, while DOXY+RIBA (1:1 combination) showed an EC50 of 4.52±1.42 μM. When compared, DOXY showed higher inhibition of viral infectivity and entry than RIBA. In contrast however, RIBA showed higher inhibition against viral replication in target cells compared to DOXY. Assays using mice as animal models revealed that DOXY+RIBA effectively inhibited CHIKV replication and attenuated its infectivity in vivo. Further experimental and clinical studies are warranted to investigate their potential application for clinical intervention of CHIKV disease. |
| doi_str_mv | 10.1371/journal.pone.0126360 |
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Here, we evaluated the antiviral effects of tetracycline (TETRA) derivatives and other common antiviral agents against CHIKV. Our results showed that within the TETRA derivatives group, Doxycycline (DOXY) exhibited the highest inhibitory effect against CHIKV replication in Vero cells. On the other hand, in the antiviral group Ribavirin (RIBA) showed higher inhibitory effects against CHIKV replication compared to Aciclovir (ACIC). Interestingly, RIBA inhibitory effects were also higher than all but DOXY within the TETRA derivatives group. Docking studies of DOXY to viral cysteine protease and E2 envelope protein showed non-competitive interaction with docking energy of -6.6±0.1 and -6.4±0.1 kcal/mol respectively. The 50% effective concentration (EC50) of DOXY and RIBA was determined to be 10.95±2.12 μM and 15.51±1.62 μM respectively, while DOXY+RIBA (1:1 combination) showed an EC50 of 4.52±1.42 μM. When compared, DOXY showed higher inhibition of viral infectivity and entry than RIBA. In contrast however, RIBA showed higher inhibition against viral replication in target cells compared to DOXY. Assays using mice as animal models revealed that DOXY+RIBA effectively inhibited CHIKV replication and attenuated its infectivity in vivo. Further experimental and clinical studies are warranted to investigate their potential application for clinical intervention of CHIKV disease.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0126360</identifier><identifier>PMID: 25970853</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animal models ; Animals ; Antibiotics ; Antiviral agents ; Antiviral Agents - pharmacology ; Antiviral Agents - therapeutic use ; Antiviral drugs ; Arthritis ; Bacterial infections ; Chikungunya Fever - drug therapy ; Chikungunya Fever - virology ; Chikungunya virus ; Chikungunya virus - drug effects ; Chlorocebus aethiops ; Cysteine ; Cysteine proteinase ; Dengue fever ; Derivatives ; Docking ; Doxycycline ; Doxycycline - pharmacology ; Doxycycline - therapeutic use ; Drug Evaluation, Preclinical ; Drug Therapy, Combination ; Drugs ; Encephalitis ; Epidemics ; Health care ; Hepatitis ; In vivo methods and tests ; Infections ; Infectivity ; Inhibition ; Ligands ; Medicine ; Mice, Inbred ICR ; Outbreaks ; Proteases ; Proteins ; Replication ; Ribavirin ; Ribavirin - pharmacology ; Ribavirin - therapeutic use ; Science ; Studies ; Vaccines ; Vector-borne diseases ; Vero Cells ; Viral envelope proteins ; Virus Attachment - drug effects ; Virus Replication - drug effects ; Viruses</subject><ispartof>PloS one, 2015-05, Vol.10 (5), p.e0126360-e0126360</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Rothan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Rothan et al 2015 Rothan et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-513ec33adcbb02d8ce012be3434ab765460a0650e93455fee0b80b411c04477a3</citedby><cites>FETCH-LOGICAL-c692t-513ec33adcbb02d8ce012be3434ab765460a0650e93455fee0b80b411c04477a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4430285/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4430285/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25970853$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rothan, Hussin A</creatorcontrib><creatorcontrib>Bahrani, Hirbod</creatorcontrib><creatorcontrib>Mohamed, Zulqarnain</creatorcontrib><creatorcontrib>Teoh, Teow Chong</creatorcontrib><creatorcontrib>Shankar, Esaki M</creatorcontrib><creatorcontrib>Rahman, Noorsaadah A</creatorcontrib><creatorcontrib>Yusof, Rohana</creatorcontrib><title>A combination of doxycycline and ribavirin alleviated chikungunya infection</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Lack of vaccine and effective antiviral drugs against chikungunya virus (CHIKV) outbreaks have led to significant impact on health care in the developing world. Here, we evaluated the antiviral effects of tetracycline (TETRA) derivatives and other common antiviral agents against CHIKV. Our results showed that within the TETRA derivatives group, Doxycycline (DOXY) exhibited the highest inhibitory effect against CHIKV replication in Vero cells. On the other hand, in the antiviral group Ribavirin (RIBA) showed higher inhibitory effects against CHIKV replication compared to Aciclovir (ACIC). Interestingly, RIBA inhibitory effects were also higher than all but DOXY within the TETRA derivatives group. Docking studies of DOXY to viral cysteine protease and E2 envelope protein showed non-competitive interaction with docking energy of -6.6±0.1 and -6.4±0.1 kcal/mol respectively. The 50% effective concentration (EC50) of DOXY and RIBA was determined to be 10.95±2.12 μM and 15.51±1.62 μM respectively, while DOXY+RIBA (1:1 combination) showed an EC50 of 4.52±1.42 μM. When compared, DOXY showed higher inhibition of viral infectivity and entry than RIBA. In contrast however, RIBA showed higher inhibition against viral replication in target cells compared to DOXY. Assays using mice as animal models revealed that DOXY+RIBA effectively inhibited CHIKV replication and attenuated its infectivity in vivo. Further experimental and clinical studies are warranted to investigate their potential application for clinical intervention of CHIKV disease.</description><subject>Animal models</subject><subject>Animals</subject><subject>Antibiotics</subject><subject>Antiviral agents</subject><subject>Antiviral Agents - pharmacology</subject><subject>Antiviral Agents - therapeutic use</subject><subject>Antiviral drugs</subject><subject>Arthritis</subject><subject>Bacterial infections</subject><subject>Chikungunya Fever - drug therapy</subject><subject>Chikungunya Fever - virology</subject><subject>Chikungunya virus</subject><subject>Chikungunya virus - drug effects</subject><subject>Chlorocebus aethiops</subject><subject>Cysteine</subject><subject>Cysteine proteinase</subject><subject>Dengue fever</subject><subject>Derivatives</subject><subject>Docking</subject><subject>Doxycycline</subject><subject>Doxycycline - pharmacology</subject><subject>Doxycycline - therapeutic use</subject><subject>Drug Evaluation, Preclinical</subject><subject>Drug Therapy, Combination</subject><subject>Drugs</subject><subject>Encephalitis</subject><subject>Epidemics</subject><subject>Health care</subject><subject>Hepatitis</subject><subject>In vivo methods and tests</subject><subject>Infections</subject><subject>Infectivity</subject><subject>Inhibition</subject><subject>Ligands</subject><subject>Medicine</subject><subject>Mice, Inbred ICR</subject><subject>Outbreaks</subject><subject>Proteases</subject><subject>Proteins</subject><subject>Replication</subject><subject>Ribavirin</subject><subject>Ribavirin - pharmacology</subject><subject>Ribavirin - therapeutic use</subject><subject>Science</subject><subject>Studies</subject><subject>Vaccines</subject><subject>Vector-borne diseases</subject><subject>Vero Cells</subject><subject>Viral envelope proteins</subject><subject>Virus Attachment - drug effects</subject><subject>Virus Replication - drug effects</subject><subject>Viruses</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl1r2zAYhc3YWLtu_2BshsHYLpJJlizbN4NQ9hFWKOzrVryWXyfKFCmV7NL8-8mNW-LRi6ELC_k5R9LRSZKXlMwpK-iHjeu9BTPfOYtzQjPBBHmUnNKKZTOREfb4aH6SPAthQ0jOSiGeJidZXhWkzNlp8m2RKrettYVOO5u6Nm3czV7tldEWU7BN6nUN19prm4IxeK2hwyZVa_2nt6ve7iHVtkU1qJ8nT1owAV-M37Pk1-dPP8-_zi4uvyzPFxczJaqsm-WUoWIMGlXXJGtKhfH0NTLOONSFyLkgQEROsGI8z1tEUpek5pQqwnlRADtLXh98d8YFOeYQJBUlKUhR8SISywPRONjInddb8HvpQMvbBedXEnynlUEpWMnbkmdcVRnPmYCKsbwSlWqbgtcij14fx936eouNQtt5MBPT6R-r13LlriXnjGTlYPBuNPDuqsfQya0OCo0Bi66_PTcdHoQP6Jt_0IdvN1IriBeI8bu4rxpM5YKzjNCYJInU_AEqjga3WsXStDquTwTvJ4LIdHjTraAPQS5_fP9_9vL3lH17xK4RTLcOzvRDZcIU5AdQeReCx_Y-ZErk0Pm7NOTQeTl2PspeHT_Qveiu5Owv42r6OQ</recordid><startdate>20150513</startdate><enddate>20150513</enddate><creator>Rothan, Hussin A</creator><creator>Bahrani, Hirbod</creator><creator>Mohamed, Zulqarnain</creator><creator>Teoh, Teow Chong</creator><creator>Shankar, Esaki M</creator><creator>Rahman, Noorsaadah A</creator><creator>Yusof, Rohana</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</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>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150513</creationdate><title>A combination of doxycycline and ribavirin alleviated chikungunya infection</title><author>Rothan, Hussin A ; Bahrani, Hirbod ; Mohamed, Zulqarnain ; Teoh, Teow Chong ; Shankar, Esaki M ; Rahman, Noorsaadah A ; Yusof, Rohana</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-513ec33adcbb02d8ce012be3434ab765460a0650e93455fee0b80b411c04477a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animal models</topic><topic>Animals</topic><topic>Antibiotics</topic><topic>Antiviral agents</topic><topic>Antiviral Agents - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rothan, Hussin A</au><au>Bahrani, Hirbod</au><au>Mohamed, Zulqarnain</au><au>Teoh, Teow Chong</au><au>Shankar, Esaki M</au><au>Rahman, Noorsaadah A</au><au>Yusof, Rohana</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A combination of doxycycline and ribavirin alleviated chikungunya infection</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-05-13</date><risdate>2015</risdate><volume>10</volume><issue>5</issue><spage>e0126360</spage><epage>e0126360</epage><pages>e0126360-e0126360</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Lack of vaccine and effective antiviral drugs against chikungunya virus (CHIKV) outbreaks have led to significant impact on health care in the developing world. Here, we evaluated the antiviral effects of tetracycline (TETRA) derivatives and other common antiviral agents against CHIKV. Our results showed that within the TETRA derivatives group, Doxycycline (DOXY) exhibited the highest inhibitory effect against CHIKV replication in Vero cells. On the other hand, in the antiviral group Ribavirin (RIBA) showed higher inhibitory effects against CHIKV replication compared to Aciclovir (ACIC). Interestingly, RIBA inhibitory effects were also higher than all but DOXY within the TETRA derivatives group. Docking studies of DOXY to viral cysteine protease and E2 envelope protein showed non-competitive interaction with docking energy of -6.6±0.1 and -6.4±0.1 kcal/mol respectively. The 50% effective concentration (EC50) of DOXY and RIBA was determined to be 10.95±2.12 μM and 15.51±1.62 μM respectively, while DOXY+RIBA (1:1 combination) showed an EC50 of 4.52±1.42 μM. When compared, DOXY showed higher inhibition of viral infectivity and entry than RIBA. In contrast however, RIBA showed higher inhibition against viral replication in target cells compared to DOXY. Assays using mice as animal models revealed that DOXY+RIBA effectively inhibited CHIKV replication and attenuated its infectivity in vivo. Further experimental and clinical studies are warranted to investigate their potential application for clinical intervention of CHIKV disease.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25970853</pmid><doi>10.1371/journal.pone.0126360</doi><tpages>e0126360</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2015-05, Vol.10 (5), p.e0126360-e0126360 |
| issn | 1932-6203 1932-6203 |
| language | eng |
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| subjects | Animal models Animals Antibiotics Antiviral agents Antiviral Agents - pharmacology Antiviral Agents - therapeutic use Antiviral drugs Arthritis Bacterial infections Chikungunya Fever - drug therapy Chikungunya Fever - virology Chikungunya virus Chikungunya virus - drug effects Chlorocebus aethiops Cysteine Cysteine proteinase Dengue fever Derivatives Docking Doxycycline Doxycycline - pharmacology Doxycycline - therapeutic use Drug Evaluation, Preclinical Drug Therapy, Combination Drugs Encephalitis Epidemics Health care Hepatitis In vivo methods and tests Infections Infectivity Inhibition Ligands Medicine Mice, Inbred ICR Outbreaks Proteases Proteins Replication Ribavirin Ribavirin - pharmacology Ribavirin - therapeutic use Science Studies Vaccines Vector-borne diseases Vero Cells Viral envelope proteins Virus Attachment - drug effects Virus Replication - drug effects Viruses |
| title | A combination of doxycycline and ribavirin alleviated chikungunya infection |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-10T00%3A31%3A15IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20combination%20of%20doxycycline%20and%20ribavirin%20alleviated%20chikungunya%20infection&rft.jtitle=PloS%20one&rft.au=Rothan,%20Hussin%20A&rft.date=2015-05-13&rft.volume=10&rft.issue=5&rft.spage=e0126360&rft.epage=e0126360&rft.pages=e0126360-e0126360&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0126360&rft_dat=%3Cgale_plos_%3EA432014340%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1680707947&rft_id=info:pmid/25970853&rft_galeid=A432014340&rft_doaj_id=oai_doaj_org_article_6384f8424c924536a9335969cfd74b65&rfr_iscdi=true |