Talk:Ebola virus disease treatment research/Archive 1

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Split Article[edit]

To all the editors that contributed to this page. Accept my humble apologies for copying and pasting when i did the split. The main article Ebola virus epidemic in West Africa was move protected so i had to copy and paste... I do realize that i have compromised the hard working contributions of others.. Regards BrianGroen (talk) 04:28, 5 January 2015 (UTC)[reply]

I'm puzzled. I also copied and pasted when I split off the Responses to the Ebola virus epidemic in West Africa article. I followed the recommended procedure at WP:PROPERSPLIT, where step 3 is to copy, and step 4 is to paste. I think you're confusing splitting with moving. Never copy and paste when MOVING an article; see Wikipedia:How to fix cut-and-paste moves for details. But splitting is different. You're moving part of an article, not all of it. I can't imagine splitting without copying and pasting the portion of the article that you are splitting off. Art LaPella (talk) 05:19, 5 January 2015 (UTC)[reply]
The confusion is partly my fault. I thought the the article had been entirely constructed at Draft:Ebola virus disease treatment and then copy-pasted from there instead of moving. See the conversation on the user's talk page. SpinningSpark 15:21, 5 January 2015 (UTC)[reply]

OK, let's work these over - copied from article - 1st bit[edit]

All of these are inappropriately described as being actual possible treatments. A single experiment on a few cells or rodents means nothing. Drugs have to trialled, found safe enough, not too toxic, and actually make some kind of commercial sense to be actual treatments These sections were built by grabbing primary sources and news reports about them, which is not a responsible way to write about anything health-related in WP. And yes, people care about these "pssoible treatments" for health reasons.

Existing drugs with possible anti-Ebola activit
text/reference

A study led by researchers at the Icahn School of Medicine and the National Institutes of Health in December 2014 identified 53 existing drugs that may be effective at preventing the Ebola virus from entering human cells. The research effort will continue in order to investigate the safety and potential effectiveness of these compounds.[1][2]

Two selective estrogen receptor modulators usually used to treat infertility and breast cancer (clomiphene and toremifene) have been found to inhibit the progress of Ebola virus in vitro as well as in infected mice. Ninety percent of the mice treated with clomiphene and 50 percent of those treated with toremifene survived the tests.[3] The study authors conclude that given their oral availability and history of human use, these drugs would be candidates for treating Ebola virus infection in remote geographical locations, either on their own or together with other antiviral drugs.

A 2014 study found that three ion channel blockers used in the treatment of irregular heart rhythms, amiodarone, dronedarone and verapamil, block the entry of Ebola virus into cells in vitro.[4] Unapproved use of amiodarone in human Ebola patients at one clinic in Sierra Leone, was however described as "reckless" and may have actually contributed to an increased likelihood of death.[5]

Lamivudine, usually used to treat HIV/AIDS, was reported by a doctor in Liberia to have been used successfully to treat 13 out of 15 Ebola-infected patients.[6] Dr Benjamin Neuman, a virologist at the University of Reading, said he would need to see the results of a larger test before drawing conclusions about any treatment.[7] An in-vitro study found no evidence of Ebola virus inhibition by lamivudine.[8]

Patients with suspected Ebola virus disease are also regularly treated for malaria in endemic areas. During a shortage of artemether–lumefantrine in Liberia, physicians used artesunate–amodiaquine as an alternative and found significantly reduced risk of death (hazard ratio 0.69) in patients without malaria but who did have Ebola.[9] However it is unclear whether the effect was due to increased risk of death from artemether-lumafantrine or decreased risk from artesunate-amodiaquine.[10]

Lack of available treatment options has spurred research into a number of other possible antivirals targeted against Ebola,[11][12] including natural products such as scytovirin and griffithsin,[13][14] as well as synthetic drugs including DZNep,[15] FGI-103, FGI-104, FGI-106, dUY11 and LJ-001,[16] and other newer agents.[17][18][19][20][21][22][23]

Researchers in Thailand claim to have developed an antibody-based treatment for Ebola using synthesized fragments of the virus. It has not been tested against Ebola itself. Scientists from the WHO and NIH have offered to test the treatment against live Ebola virus, but there is still a great deal of development needed before human trials.[24]

The Russian Academy of Sciences has developed an anti-viral drug called Triazavirin, which is said to be effective against influenza and Lassa fever as well as Ebola and Marburg filoviruses, and might be available for clinical trials in 2015.[25][26][27]

The compound Tetrandrine derived from a Chinese medicinal herb has been shown in vitro to inhibit release of Ebola virus from the macropinosomes in which they enter the host cells, thereby trapping them and preventing replication. The compound also showed therapeutic efficacy against Ebola virus in preliminary studies on mice.[28][29]

References

  1. ^ Kouznetsova, Jennifer; Sun, Wei; Martínez-Romero, Carles; Tawa, Gregory; Shinn, Paul; Chen, Catherine Z; Schimmer, Aaron; Sanderson, Philip; McKew, John C; Zheng, Wei; García-Sastre, Adolfo (17 December 2014). "Identification of 53 compounds that block Ebola virus-like particle entry via a repurposing screen of approved drugs". Emerging Microbes & Infections. 3 (12): e84. doi:10.1038/emi.2014.88.
  2. ^ "53 Ebola-blocking drugs identified among existing medications". Retrieved 7 January 2015.
  3. ^ Johansen LM, Brannan JM, Delos SE, Shoemaker CJ, Stossel A, Lear C, Hoffstrom BG, Dewald LE, Schornberg KL, Scully C, Lehár J, Hensley LE, White JM, Olinger GG; Brannan; Delos; Shoemaker; Stossel; Lear; Hoffstrom; Dewald; Schornberg; Scully; Lehár; Hensley; White; Olinger (June 2013). "FDA-approved selective estrogen receptor modulators inhibit Ebola virus infection". Sci Transl Med. 5 (190): 190ra79. doi:10.1126/scitranslmed.3005471. PMC 3955358. PMID 23785035. {{cite journal}}: Unknown parameter |laysource= ignored (help); Unknown parameter |laysummary= ignored (help)CS1 maint: multiple names: authors list (link)
  4. ^ Gehring G, Rohrmann K, Atenchong N, Mittler E, Becker S, Dahlmann F, Pöhlmann S, Vondran FW, David S, Manns MP, Ciesek S, von Hahn T; Rohrmann; Atenchong; Mittler; Becker; Dahlmann; Pöhlmann; Vondran; David; Manns; Ciesek; von Hahn (2014). "The clinically approved drugs amiodarone, dronedarone and verapamil inhibit filovirus cell entry". J. Antimicrob. Chemother. 69 (8): 2123–31. doi:10.1093/jac/dku091. PMID 24710028.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  5. ^ Untested Ebola drug given to patients in Sierra Leone causes UK walkout. Sarah Boseley, The Guardian, 22 December 2014
  6. ^ "Doctor treats Ebola with HIV drug in Liberia – seemingly successfully. Elizabeth Cohen, CNN news. 29 September 2014". CNN. 27 September 2014. Retrieved 7 October 2014.
  7. ^ "Ebola virus outbreak: Liberia doctor treating patients with HIV drugs reports success". The Independent. Retrieved 7 January 2015.
  8. ^ Hensley, Lisa E.; Dyall, Julie; Olinger, Gene G.; Jahrling, Peter B. "Lack of Effect of Lamivudine on Ebola Virus Replication". Emerging Infectious Diseases. 21 (3): 550–552. doi:10.3201/eid2103.141862. PMC 4344292. PMID 25695153.
  9. ^ Gignoux, Etienne; Azman, Andrew S.; de Smet, Martin; Azuma, Philippe; Massaquoi, Moses; Job, Dorian; Tiffany, Amanda; Petrucci, Roberta; Sterk, Esther (2016-01-07). "Effect of Artesunate–Amodiaquine on Mortality Related to Ebola Virus Disease". New England Journal of Medicine. 374 (1): 23–32. doi:10.1056/NEJMoa1504605. ISSN 0028-4793. PMID 26735991.
  10. ^ "Could a Second-Line Antimalarial Treatment Benefit Patients with Ebola Virus Disease?". www.jwatch.org. 2016-01-06. doi:10.1056/nejm-jw.NA40055. Retrieved 2016-01-11.
  11. ^ Bray M, Paragas J (2002). "Experimental therapy of filovirus infections". Antiviral Res. 54 (1): 1–17. doi:10.1016/S0166-3542(02)00005-0. PMID 11888653.
  12. ^ Bray M (2003). "Defense against filoviruses used as biological weapons". Antiviral Res. 57 (1–2): 53–60. doi:10.1016/S0166-3542(02)00200-0. PMID 12615303.
  13. ^ Garrison AR, Giomarelli BG, Lear-Rooney CM, Saucedo CJ, Yellayi S, Krumpe LR, Rose M, Paragas J, Bray M, Olinger GG, McMahon JB, Huggins J, O'Keefe BR (2014). "The cyanobacterial lectin scytovirin displays potent in vitro and in vivo activity against Zaire Ebola virus". Antiviral Research. 112C: 1–7. doi:10.1016/j.antiviral.2014.09.012. PMID 25265598.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  14. ^ Barton C, Kouokam JC, Lasnik AB, Foreman O, Cambon A, Brock G, Montefiori DC, Vojdani F, McCormick AA, O'Keefe BR, Palmer KE (2014). "Activity of and effect of subcutaneous treatment with the broad-spectrum antiviral lectin griffithsin in two laboratory rodent models". Antimicrobial Agents and Chemotherapy. 58 (1): 120–7. doi:10.1128/AAC.01407-13. PMC 3910741. PMID 24145548.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  15. ^ Huggins J, Zhang ZX, Bray M (1999). "Antiviral drug therapy of filovirus infections: S-adenosylhomocysteine hydrolase inhibitors inhibit Ebola virus in vitro and in a lethal mouse model". J. Infect. Dis. 179 Suppl 1: S240–7. doi:10.1086/514316. PMID 9988190.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  16. ^ De Clercq E (2013). "A Cutting-Edge View on the Current State of Antiviral Drug Development". Medicinal Research Reviews: n/a. doi:10.1002/med.21281. PMID 23495004.
  17. ^ Kolokoltsov A; et al. (2012). "Inhibition of Lassa virus and Ebola virus infection in host cells treated with the kinase inhibitors genistein and tyrphostin". Archives of Virology. 157 (1): 121–127. doi:10.1007/s00705-011-1115-8.
  18. ^ Panchal RG, Reid SP, Tran JP, Bergeron AA, Wells J, Kota KP, Aman J, Bavari S (January 2012). "Identification of an antioxidant small-molecule with broad-spectrum antiviral activity". Antiviral Res. 93 (1): 23–9. doi:10.1016/j.antiviral.2011.10.011. PMID 22027648.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  19. ^ Qiu X, Wong G, Fernando L, Ennis J, Turner JD, Alimonti JB, Yao X, Kobinger GP (July 2013). "Monoclonal antibodies combined with adenovirus-vectored interferon significantly extend the treatment window in Ebola virus-infected guinea pigs". J. Virol. 87 (13): 7754–7. doi:10.1128/JVI.00173-13. PMC 3700280. PMID 23616649.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  20. ^ Elshabrawy HA, Fan J, Haddad CS, Ratia K, Broder CC, Caffrey M, Prabhakar BS (April 2014). "Identification of a broad-spectrum antiviral small molecule against severe acute respiratory syndrome coronavirus and Ebola, Hendra, and Nipah viruses by using a novel high-throughput screening assay". Journal of Virology. 88 (8): 4353–65. doi:10.1128/JVI.03050-13. PMC 3993759. PMID 24501399.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  21. ^ Mudhasani R, Kota KP, Retterer C, Tran JP, Whitehouse CA, Bavari S (August 2014). "High content image-based screening of a protease inhibitor library reveals compounds broadly active against Rift Valley fever virus and other highly pathogenic RNA viruses". PLoS Neglected Tropical Diseases. 8 (8): e3095. doi:10.1371/journal.pntd.0003095. PMC 4140764. PMID 25144302.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  22. ^ Johnson JC, Martinez O, Honko AN, Hensley LE, Olinger GG, Basler CF (June 2014). "Pyridinyl imidazole inhibitors of p38 MAP kinase impair viral entry and reduce cytokine induction by Zaire ebolavirus in human dendritic cells". Antiviral Research. 107: 102–9. doi:10.1016/j.antiviral.2014.04.014. PMC 4103912. PMID 24815087.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  23. ^ Madrid, PB; Chopra, S; Manger, ID; Gilfillan, L; Keepers, TR; Shurtleff, AC; Green, CE; Iyer, LV; Dilks, HH; Davey, RA; Kolokoltsov, AA; Carrion R, Jr; Patterson, JL; Bavari, S; Panchal, RG; Warren, TK; Wells, JB; Moos, WH; Burke, RL; Tanga, MJ (2013). "A systematic screen of FDA-approved drugs for inhibitors of biological threat agents". PLOS ONE. 8 (4): e60579. doi:10.1371/journal.pone.0060579. PMID 23577127.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  24. ^ "Thai researchers claim breakthrough in Ebola treatment. Ron Corben, Voice of America News, 3 October 2014". VOA.
  25. ^ "Target: Ebola". Pravda. Retrieved 18 January 2015.
  26. ^ "Yekaterinburg pharmacies to sell domestic antiviral drug". Retrieved 18 January 2015.
  27. ^ "Ebola crisis: Vaccine 'too late' for outbreak. BBC News, 17 October 2014". BBC News.
  28. ^ Dunham, Will (26 February 2015). "Compound from Chinese medicinal herb shows promise for Ebola". Reuters. Retrieved 27 Feb 2015.
  29. ^ Sakurai Y; et al. (27 February 2015). "Two-pore channels control Ebola virus host cell entry and are drug targets for disease treatment". Science. 347 (6225): 995–8. doi:10.1126/science.1258758.

Jytdog (talk) 07:09, 17 March 2016 (UTC)[reply]

Well...triazavirin at least is certainly an actual possible treatment for Ebola, it is a broad-spectrum antiviral drug which is well advanced through trials in Russia against various viral diseases. Media reports at the time suggested it was being distributed to Russian healthcare workers helping out with the Ebola crisis (though I'll concede Russian media reports are probably not RS), but it is certainly a notable potential treatment, the fact most of the sources are in Russian doesn't make it any less notable. The rest of this content, well it certainly needs to be trimmed a bit, and much of it is sourced inadequately. However I do object to deleting all content that is sourced from reputable journals, this is useful encyclopedic content that many people will be interested in, and I suppose the key point is that these are experimental treatments, by definition they are not being used medically in humans yet, and indeed may never be, so it is too much of a stretch to say that WP:MEDRS applies here. The whole point of the strict sourcing required by that guideline is to avoid giving inappropriately sourced medical advice, it is not meant to constrain discussion of experimental drugs. Wikipedia has hundreds of articles about compounds used only in research that are not ever intended to be used as medicines in humans, and things like those FGI- series compounds are notable as experimental antiviral compounds in their own right. It is not appropriate to delete this content merely on the grounds that it is not supported by MEDRS compliant reviews. Just because an article has something to do with medicine does not mean that everything in there has to meet MEDRS, this has been discussed quite recently iirc. Meodipt (talk) 07:32, 17 March 2016 (UTC)[reply]

break[edit]

i am happy to work with you on this. let's go paragraph by paragraph. The first paragraph is about results of the use of an in vitro HTS, that measures whether virus-like particles with VP40 on their surface enter cells or not. They also did a counter-screen for cell toxicity. That's it. The content is supported by a primary source and a press release. What do you think about this content? Jytdog (talk) 17:08, 17 March 2016 (UTC)[reply]
Right, well I think most of these paragraphs can be condensed together into one or two lines, and just have a long list of references after them. Now that the Ebola outbreak is over we are looking at it from more of a historical perspective, and I think its important to capture that sense of how since there was no treatment for it, researchers everywhere were scrambling to find anything that might work. Also use of things like lamivudine and amiodarone is worth noting, as again it illustrates the desperation of clinicians working in the area that they were willing to try untested and potentially dangerous treatments in the absence of anything better being available. But yes I totally agree that we shouldn't be overstating the significance of the results or presenting them as actual potential treatments. How about condensing this whole section to;

"A large number of existing drugs have been screened for anti-Ebola activity in vitro, and some of these such as toremiphene and tetrandrine have also shown in vivo activity in tests on mice. However in most cases these results would not be applicable to humans, as the doses required to produce anti-Ebola activity fall well outside the safe dosage range in humans. Unapproved use of amiodarone at one clinic in Sierra Leone was described as "reckless" and may have actually contributed to an increased likelihood of death. Similarly correlations reported on the basis of a small number of case reports have proved to be unreliable when studied in more detail, for instance lamivudine treatment was anecdotally reported to result in an apparent increase in survival in some Ebola patients, but subsequent studies have not shown any evidence for anti-Ebola activity from lamivudine. Lack of available treatment options also renewed interest in a number of broad-spectrum antiviral drugs that had been researched previously, but these are mainly relevant as lead compounds from which future anti-Ebola drugs might be developed, rather than viable treatments in their own right."

I think this would cover pretty much all the references that are worth retaining from this section, except for triazavirin. As I said that one should really be moved up to the "Experimental treatments being researched" section, but finding a suitable reference to support this might be tricky unless we can find someone who can search for it in Russian-language journals, I couldn't find any suitable RS in English when I looked before. Meodipt (talk) 19:52, 17 March 2016 (UTC)[reply]
That is way, WAY better content for this section, to the extent all that can be reliably sourced. Rock on with that. Thanks! Jytdog (talk) 20:21, 17 March 2016 (UTC)[reply]
Ideal sources would be something like a review that discussed all this scrambling. There must be one now.. let me look.... Jytdog (talk) 20:24, 17 March 2016 (UTC)[reply]
PMID 26913314 has some useful stuff, as does PMID 25713700 and PMID 25630412 although the latter is a year old. It would be best to source from these rather than the primary studies.... Jytdog (talk) 20:31, 17 March 2016 (UTC)[reply]
this too Jytdog (talk) 20:36, 17 March 2016 (UTC)[reply]
Great, I'll have a look through those. I shouldn't think it will be too hard to come to a consensus text that summarises all this scramble of research efforts without overstating its significance. Meodipt (talk) 21:11, 17 March 2016 (UTC)[reply]

Potential diagnostic tests[edit]

above section might need expansion--Ozzie10aaaa (talk) 20:51, 18 September 2016 (UTC)[reply]


favipiravir[edit]

treatment?[edit]

[1]--Ozzie10aaaa (talk) 11:25, 14 January 2019 (UTC)[reply]

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