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Coxsackie B virus
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==Antivirals and immunomodulators for coxsackievirus B == === Interferon === Treatment of enterovirus-associated ME/CFS with a course of [[Interferon]] (or interferon plus the antiviral [[Ribavirin]]) over a few months results in dramatic improvements, allowing many severe bedbound ME/CFS patients being able to return to work. However, these improvements achieved with interferon typically only last for a short period of a few months to a year, after which relapse usually occurs.<ref name="Chia2005">{{Cite journal | last = Chia | first = J.K.S. | date = 2005-11-01 | title = The role of enterovirus in chronic fatigue syndrome | url =https://jcp.bmj.com/content/58/11/1126|journal=Journal of Clinical Pathology|language=en|volume=58|issue=11 | pages = 1126â1132|doi=10.1136/jcp.2004.020255|issn=0021-9746|pmid=16254097|quote=The results of antiviral treatment provided supportive evidence for the pathogenic role of RNA in patients with CFS.|via=}}</ref> Repeated treatment with interferon is usually not feasible, as patients typically eventually develop antibodies against recombinant interferon, which disables this drug. Thus interferon clearly demonstrates that inhibiting the enteroviruses associated with ME/CFS results in large improvements in symptoms; but interferon type 1 and 2 is not effective as a cure or long-term treatment of ME/CFS. Dr John Chia finds interferon type 1 and 2 works for ME/CFS associated with coxsackievirus B3 and B5, but is not effective against coxsackievirus B4.<ref name="conf">{{Cite web | url = http://www.investinme.org/IIMEC4.shtml | title = Diagnosis and Treatment of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome Associated with Chronic Enterovirus Infection. Presentation at the Invest in ME International ME Conference, London 2009 (available on DVD). Timecode: 42:31. | last = Chia | first = John | date = 2009 | website = | archive-url = | archive-date = |url-status = | access-date=|quote=Interestingly enough, my son also has coxsackie B4, and for coxsackie B4, the antibody titer did not change at all, which is what I usually see using ribavirin and interferon; it is ineffective against coxsackie B4.}}</ref> === Oxymatrine === The mainstay of Dr Chia's treatment of enterovirus-associated ME/CFS is the immunomodulator [[oxymatrine]], which Chia found in an [http://forums.phoenixrising.me/index.php?threads/i-start-to-relapse-every-time-i-come-off-equilibrant.40479/#post-650624 informal study] leads to 30% of ME/CFS patients making a major improvement, and another 20% will make more minor improvements. Dr Chia often adds the immunomodulator inosine to oxymatrine. He also uses the antiviral Epivir (lamivudine) to treat enterovirus ME/CFS.<ref>{{Cite web | url = https://www.healthrising.org/blog/2014/02/18/this-really-happening-one-year-dr-chia-chronic-fatigue-syndrome-patient-reports/ | title = âCould This Really Be Happeningâ? One Year With Dr. Chia â A Chronic Fatigue Syndrome Patient Reports | last = McLaughlin | first = Christine | authorlink = | date = Feb 18, 2014 | website = | archive-url = | archive-date = |url-status = | access-date=}}</ref> === Ampligen === The immunomodulatory drug [[Ampligen]] (rintatolimod) is a treatment that has proven effective for ME/CFS in clinical trials, and in mouse models, Ampligen was found to be protective of coxsackievirus B3 [[myocarditis]].<ref>{{Cite journal | url = https://www.ncbi.nlm.nih.gov/pubmed/14693549 | title = The interferon inducer ampligen [poly(I)-poly(C12U)] markedly protects mice against coxsackie B3 virus-induced myocarditis | last = Padalko|first = E | date = January 2004|journal=Antimicrobial Agents and Chemotherapy|volume=48 | pages = 267-74|via=}}</ref> === Pleconaril === One ME/CFS patient with [[Coxsackievirus B4|coxsackievirus B4]] experienced moderate improvement on the antiviral drug [[Pleconaril]] for one month, along with a fourfold decrease of antibody titers for CVB4 and echoviruses 7 and 11. However on discontinuation of the drug the patient relapsed about one month later, and did not respond to a further month of treatment. Pleconaril is no longer available for investigational use.<ref name=":0" /> === Rega Compound === Two potent new antiviral drugs for coxsackievirus B code named '''Rega Compound A''' and '''Rega Compound 17''' are expected to become available in around 2021. These two drugs were originally developed by the Rega Institute in Belgium (info [https://forums.phoenixrising.me/threads/rega-compound-17-compound-a-potential-cures-for-chronic-coxsackie-b.52128/ here]). Dr Chia believes these drugs may be effective treatments for enterovirus-associated ME/CFS. === Supplements === [[Selenium]] deficiency increases the virulence of coxsackievirus B3 infections in a mouse model.<ref>http://jn.nutrition.org/content/130/2/485S.full</ref> Drugs and supplements which may have some mild in vivo antiviral effects (at least in murine studies) against coxsackievirus B include: sophoridine (Sophora root extract),<ref>{{Cite journal | last = Zhang|first = Yuanyuan | last2 = Zhu | first2 = Haiyan | last3 = Ye | first3 = Guan | last4 = Huang | first4 = Chenggang | last5 = Yang | first5 = Yingzhen | last6 = Chen | first6 = Ruizhen | last7 = Yu | first7 = Yong | last8 = Cui | first8 = Xiaolan | date = 2006-03-20 | title = Antiviral effects of sophoridine against coxsackievirus B3 and its pharmacokinetics in rats |url =https://www.ncbi.nlm.nih.gov/pubmed/16309710|journal=Life Sciences|volume=78|issue=17 | pages = 1998â2005|doi=10.1016/j.lfs.2005.09.034|issn=0024-3205|pmid=16309710}}</ref> Arbidol (umifenovir),<ref>{{Cite journal | last = Shi|first = L. | last2 = Xiong | first2 = H. | last3 = He | first3 = J. | last4 = Deng | first4 = H. | last5 = Li | first5 = Q. | last6 = Zhong | first6 = Q. | last7 = Hou | first7 = W. | last8 = Cheng | first8 = L. | last9 = Xiao | first9 = H. | date = 2007 | title=Antiviral activity of arbidol against influenza A virus, respiratory syncytial virus, rhinovirus, coxsackie virus and adenovirus in vitro and in vivo | url = https://www.ncbi.nlm.nih.gov/pubmed/17497238|journal=Archives of Virology|volume=152|issue=8 | pages = 1447â1455|doi=10.1007/s00705-007-0974-5|issn=0304-8608|pmid=17497238}}</ref><ref>{{Cite journal | last = Zhong|first = Qiong | last2 = Yang | first2 = Zhanqiu | last3 = Liu | first3 = Yuanyuan | last4 = Deng | first4 = Haiying | last5 = Xiao | first5 = Hong | last6 = Shi | first6 = Liqiao | last7 = He | first7 = Jing | date = 2009 | title = Antiviral activity of Arbidol against Coxsackie virus B5 in vitro and in vivo | url = https://www.ncbi.nlm.nih.gov/pubmed/19291363|journal=Archives of Virology|volume=154|issue=4 | pages = 601â607|doi=10.1007/s00705-009-0346-4|issn=1432-8798|pmid=19291363}}</ref> astragaloside IV (from Astragalus membranous),<ref>{{Cite journal | last = Zhang|first = Yuanyuan | last2 = Zhu | first2 = Haiyan | last3 = Huang | first3 = Chenggang | last4 = Cui | first4 = Xiaolan | last5 = Gao | first5 = Yingjie | last6 = Huang | first6 = Yang | last7 = Gong | first7 = Wenfeng | last8 = Zhao | first8 = Ye | last9 = Guo | first9 = Shanshan | date = Feb 2006 | title = Astragaloside IV exerts antiviral effects against coxsackievirus B3 by upregulating interferon-gamma | url = https://www.ncbi.nlm.nih.gov/pubmed/16495755|journal=Journal of Cardiovascular Pharmacology|volume=47|issue=2 | pages = 190â195|doi=10.1097/01.fjc.0000199683.43448.64|issn=0160-2446|pmid=16495755}}</ref> cinnamic acid (a metabolite of cinnamon spice),<ref>{{Cite journal | last = Ding|first = YuanYuan | last2 = Qiu | first2 = Lin | last3 = Zhao | first3 = GangTao | last4 = Xu | first4 = Jingfeng | last5 = Wang | first5 = Siwang | date = Aug 2010 | title = Influence of cinnamaldehyde on viral myocarditis in mice | url =https://www.ncbi.nlm.nih.gov/pubmed/20460981|journal=The American Journal of the Medical Sciences|volume=340|issue=2 | pages = 114â120|doi=10.1097/MAJ.0b013e3181dd3b43|issn=1538-2990|pmid=20460981}}</ref> emodin (from Rheum palmatum),<ref>{{Cite journal | last = Liu|first = Zhao | last2 = Wei | first2 = Fei | last3 = Chen | first3 = Liang-Jun | last4 = Xiong | first4 = Hai-Rong | last5 = Liu | first5 = Yuan-Yuan | last6 = Luo | first6 = Fan | last7 = Hou | first7 = Wei | last8 = Xiao | first8 = Hong | last9 = Yang | first9 = Zhan-Qiu | date = 2013-09-25 | title = In vitro and in vivo studies of the inhibitory effects of emodin isolated from Polygonum cuspidatum on Coxsakievirus Bâ | url = https://www.ncbi.nlm.nih.gov/pubmed/24071990|journal=Molecules (Basel, Switzerland)|volume=18|issue=10 | pages = 11842â11858|doi=10.3390/molecules181011842|issn=1420-3049|pmc=|pmid=24071990}}</ref> dihydroquercetin (DHQ),<ref>{{Cite journal | last = Galochkina | first = Anastasia V. | last2 = Anikin | first2 = Vadim B. | last3 = Babkin | first3 = Vasily A. | last4 = Ostrouhova | first4 = Liudmila A. | last5 = Zarubaev | first5 = Vladimir V. | date = Apr 2016 | title = Virus-inhibiting activity of dihydroquercetin, a flavonoid from Larix sibirica, against coxsackievirus B4 in a model of viral pancreatitis |url =https://www.ncbi.nlm.nih.gov/pubmed/26780775|journal=Archives of Virology|volume=161|issue=4 | pages = 929â938|doi=10.1007/s00705-016-2749-3|issn=1432-8798|pmid=26780775}}</ref> arsenic trioxide,<ref>{{Cite journal | last = Molin | first = Ylva | last2 = Frisk | first2 = Peter | last3 = Hjelm | first3 = Eva | last4 = Blomberg | first4 = Jonas | last5 = Friman | first5 = GĂśran | last6 = Ilbäck | first6 = Nils-Gunnar | date = Nov 2010 | title = Arsenic trioxide influences viral replication in target organs of coxsackievirus B3-infected mice | url =https://www.ncbi.nlm.nih.gov/pubmed/20638482|journal=Microbes and Infection|volume=12|issue=12-13 | pages = 1027â1034|doi=10.1016/j.micinf.2010.07.003|issn=1769-714X|pmid=20638482}}</ref> Spatholobus suberectus (Ji Xue Teng),<ref>{{Cite journal | last = Pang|first = Ji | last2 = Guo | first2 = Jin-peng | last3 = Jin | first3 = Min | last4 = Chen | first4 = Zhi-qiang | last5 = Wang | first5 = Xin-wei | last6 = Li | first6 = Jun-Wen | date = Oct 2011 | title = Antiviral effects of aqueous extract from Spatholobus suberectus Dunn. against coxsackievirus B3 in mice | url =https://www.ncbi.nlm.nih.gov/pubmed/21717161|journal=Chinese Journal of Integrative Medicine|volume=17|issue=10 | pages = 764â769|doi=10.1007/s11655-011-0642-1|issn=1672-0415|pmid=21717161}}</ref> salidroside (from Rhodiola rosea),<ref>{{Cite journal | last = Wang|first = Haibo | last2 = Ding | first2 = Yuanyuan | last3 = Zhou | first3 = Jun | last4 = Sun | first4 = Xiaoli | last5 = Wang | first5 = Siwang | date = Mar 2009 | title = The in vitro and in vivo antiviral effects of salidroside from Rhodiola rosea L. against coxsackievirus B3 | url = https://www.ncbi.nlm.nih.gov/pubmed/18818064|journal=Phytomedicine: International Journal of Phytotherapy and Phytopharmacology|volume=16|issue=2-3 | pages = 146â155|doi=10.1016/j.phymed.2008.07.013|issn=1618-095X|pmid=18818064}}</ref> and quercetin.<ref>{{Cite journal | last = Colunga Biancatelli|first = Ruben Manuel Luciano | last2 = Berrill | first2 = Max | last3 = Catravas | first3 = John D. | last4 = Marik | first4 = Paul E. | date = 2020 | title=Quercetin and Vitamin C: An Experimental, Synergistic Therapy for the Prevention and Treatment of SARS-CoV-2 Related Disease (COVID-19) | url = https://www.frontiersin.org/articles/10.3389/fimmu.2020.01451/full|journal=Frontiers in Immunology|language=English|volume=11|doi=10.3389/fimmu.2020.01451|issn=1664-3224}}</ref> Drugs and supplements which have in vitro antiviral effects against coxsackievirus B are listed [https://forums.phoenixrising.me/threads/enteroviruses-revisted.14478/#post-238690 here] (but typically in vitro antiviral activity does not translate to in vivo efficacy when the compound is taken orally, so these compounds are likely to have no therapeutic effect, but may be of interest as lead compounds in the development of new antiviral drugs). [[N-acetylcysteine|N-acetyl cysteine (NAC)]] has been proven to effectively treat Coxsackivirus B3 in vivo.<ref>{{Cite journal | last = Wang|first = Yao | last2 = Zhao | first2 = Shuoxuan | last3 = Chen | first3 = Yang | last4 = Wang | first4 = Ying | last5 = Wang | first5 = Tianying | last6 = Wo | first6 = Xiaoman | last7 = Dong | first7 = Yanyan | last8 = Zhang | first8 = Jian | last9 = Xu | first9 = Weizhen | date = 2020-07-01 | title = N-Acetyl cysteine effectively alleviates Coxsackievirus B-Induced myocarditis through suppressing viral replication and inflammatory response | url =http://www.sciencedirect.com/science/article/pii/S0166354219304735|journal=Antiviral Research|language=en|volume=179 | pages = 104699|doi=10.1016/j.antiviral.2019.104699|issn=0166-3542}}</ref>
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