Favipiravir: Perbedaan antara revisi

'''Favipiravir''', atau yang dikenal dengan nama '''Avigan''' dan '''favilavir''' adalah [[obat antivirus]] yang dikembangkan oleh [[ FUJIFILM Toyama Chemical Co, Ltd |Toyama Chemical]] (anak perusahaan [[Fujifilm]]). Obat ini memiliki aktivitas melawan berbagai [[virus RNA]]. Senyawa antivirus ini merupakan turunan dari [[Pirazinamid|pirazinkarboksamida]]. Dalam percobaan yang dilakukan pada hewan, Favipiravirfavipiravir menunjukkan adanya aktivitas melawan [[Orthomyxoviridae|virus influenza]], [[virus West Nile]], [[Demam kuning|virus demam kuning]], [[Virus penyakit mulut dan kuku|virus penyakit mulut dan kuku,]], [[flavivirus]], [[ Arenavirus |arenavirus]], [[ Bunyavirus |bunyavirus]], dan [[ Alphavirus |alphavirus]].<ref name="Furuta">{{Cite journal|date=Juni 2009|title=T-705 (favipiravir) and related compounds: Novel broad-spectrum inhibitors of RNA viral infections|journal=Antiviral Research|volume=82|issue=3|pages=95–102|doi=10.1016/j.antiviral.2009.02.198|pmc=|pmid=19428599|vauthors=Furuta Y, Takahashi K, Shiraki K, Sakamoto K, Smee DF, Barnard DL, Gowen BB, Julander JG, Morrey JD}}</ref> Selain itu, Favipiravirfavipiravir juga menunjukkan adanya aktivitas melawan [[ Enterovirus |enterovirus]]<ref name="Furuta2013">{{Cite journal|date=November 2013|title=Favipiravir (T-705), a novel viral RNA polymerase inhibitor|journal=Antiviral Research|volume=100|issue=2|pages=446–54|doi=10.1016/j.antiviral.2013.09.015|pmc=3880838|pmid=24084488|vauthors=Furuta Y, Gowen BB, Takahashi K, Shiraki K, Smee DF, Barnard DL}}</ref> dan virus [[demam lembah rift]].<ref>{{Cite journal|date=April 2014|title=Broad spectrum antiviral activity of favipiravir (T-705): protection from highly lethal inhalational Rift Valley Fever|journal=PLoS Neglected Tropical Diseases|volume=8|issue=4|pages=e2790|doi=10.1371/journal.pntd.0002790|pmc=3983105|pmid=24722586|vauthors=Caroline AL, Powell DS, Bethel LM, Oury TD, Reed DS, Hartman AL}}</ref> Favipiravir juga memiliki efektivitas yang terbatas terhadap [[virus Zika]] dalam penelitian pada hewan.<ref>{{Cite journal|year=2016|title=Zika Virus: Where Is the Treatment?|journal=Current Treatment Options in Infectious Diseases|volume=8|issue=3|pages=208–11|doi=10.1007/s40506-016-0083-7|pmc=4969322|pmid=27547128|vauthors=Mumtaz N, van Kampen JJ, Reusken CB, Boucher CA, Koopmans MP}}</ref> Obat ini juga menunjukkan efektivitas melawan [[rabies]].<ref>{{Cite journal|date=April 2016|title=Efficacy of Favipiravir (T-705) in Rabies Postexposure Prophylaxis|journal=The Journal of Infectious Diseases|volume=213|issue=8|pages=1253–61|doi=10.1093/infdis/jiv586|pmc=4799667|pmid=26655300|vauthors=Yamada K, Noguchi K, Komeno T, Furuta Y, Nishizono A}}</ref> Favipiravir telah digunakan secara eksperimental pada beberapa pasien yang terinfeksi virus.<ref>{{Cite journal|date=Januari 2019|title=Human Rabies - Virginia, 2017|journal=MMWR. Morbidity and Mortality Weekly Report|language=en-us|volume=67|issue=5152|pages=1410–14|doi=10.15585/mmwr.mm675152a2|pmc=6334827|pmid=30605446|vauthors=Murphy J, Sifri CD, Pruitt R, Hornberger M, Bonds D, Blanton J, Ellison J, Cagnina RE, Enfield KB, Shiferaw M, Gigante C, Condori E, Gruszynski K, Wallace RM}}</ref>

Pada Februari 2020, Favipiravirfavipiravir sedang diteliti di Tiongkok sebagai pengobatan terhadap [[penyakit koronavirus 2019]].<ref>Li G, De Clercq E. Therapeutic options for the 2019 novel coronavirus (2019-nCoV). ''Nature Reviews Drug Discovery'' 2020 Feb {{Doi|10.1038/d41573-020-00016-0}}</ref><ref>[https://www.reuters.com/article/brief-corrected-zhejiang-hisun-pharma-ge/brief-corrected-zhejiang-hisun-pharma-gets-approval-for-clinical-trial-to-test-flu-drug-favipiravir-for-pneumonia-caused-by-new-coronavirus-idUSL4N2AH0C8 BRIEF-Corrected-Zhejiang Hisun Pharma gets approval for clinical trial to test flu drug Favipiravir for pneumonia caused by new coronavirus] {{Webarchive|url=https://web.archive.org/web/20200313121919/https://www.reuters.com/article/brief-corrected-zhejiang-hisun-pharma-ge/brief-corrected-zhejiang-hisun-pharma-gets-approval-for-clinical-trial-to-test-flu-drug-favipiravir-for-pneumonia-caused-by-new-coronavirus-idUSL4N2AH0C8 |date=2020-03-13 }}. Reuters Healthcare, 20 Maret 2020.</ref> Pada 17 Maret, pejabat pemerintah Tiongkok mengatakan bahwa Favipiravirfavipiravir efektif dalam mengobati penyakit koronavirus di Wuhan dan Shenzhen.<ref>[{{Cite web |url=https://www3.nhk.or.jp/nhkworld/en/news/20200317_48/ |title=NHK World News ‘China: Avigan effective in tackling coronavirus’] |access-date=2020-03-20 |archive-date=2020-03-18 |archive-url=https://web.archive.org/web/20200318153606/https://www3.nhk.or.jp/nhkworld/en/news/20200317_48/ |dead-url=yes }}</ref><ref>[{{Cite web |url=http://www.xinhuanet.com/english/2020-03/17/c_138887971.htm |title=Huaxia. "Favipiravir shows good clinical efficacy in treating COVID-19: official." Xinhuanet.com, 17 Maret 2020] |access-date=2020-03-20 |archive-date=2020-03-18 |archive-url=https://web.archive.org/web/20200318203201/http://www.xinhuanet.com/english/2020-03/17/c_138887971.htm |dead-url=yes }}</ref>

Dugaan mekanismeMekanisme kerja obat ini adalahdiduga dengan penghambatanmenghambat secara selektif polimerase RNA dependen RNA dari virus.<ref>{{Cite journal|year=2013|title=The ambiguous base-pairing and high substrate efficiency of T-705 (Favipiravir) Ribofuranosyl 5'-triphosphate towards influenza A virus polymerase|journal=PLOS ONE|volume=8|issue=7|pages=e68347|bibcode=2013PLoSO...868347J|doi=10.1371/journal.pone.0068347|pmc=3707847|pmid=23874596|vauthors=Jin Z, Smith LK, Rajwanshi VK, Kim B, Deval J}}</ref> Penelitian lain menunjukkan bahwa favipiravir menrangsangmerangsang mutasi transversi RNA yang mematikan bagi virus.<ref>{{Cite journal|date=April 2013|title=T-705 (favipiravir) induces lethal mutagenesis in influenza A H1N1 viruses in vitro|journal=Journal of Virology|volume=87|issue=7|pages=3741–51|doi=10.1128/JVI.02346-12|pmc=3624194|pmid=23325689|vauthors=Baranovich T, Wong SS, Armstrong J, Marjuki H, Webby RJ, Webster RG, Govorkova EA}}</ref> Favipiravir merupakan [[bakal obat]] yang harus melewati proses metabolisme sebelum dapat memberikan efek antivirus. Metabolit tersebut adalah favipiravir-ribofuranosil-5'-trifosfat (favipiravir-RTP). Favipiravir tersedia dalam bentuk tablet dan injeksi intravena.<ref>{{Cite journal|displayauthors=6|date=Maret 2018|title=Antiviral efficacy of favipiravir against Ebola virus: A translational study in cynomolgus macaques|journal=PLoS Medicine|volume=15|issue=3|pages=e1002535|doi=10.1371/journal.pmed.1002535|pmc=5870946|pmid=29584730|vauthors=Guedj J, Piorkowski G, Jacquot F, Madelain V, Nguyen TH, Rodallec A, Gunther S, Carbonnelle C, Mentré F, Raoul H, de Lamballerie X}}</ref><ref>{{Cite journal|date=Oktober 2009|title=Intracellular metabolism of favipiravir (T-705) in uninfected and influenza A (H5N1) virus-infected cells|journal=The Journal of Antimicrobial Chemotherapy|volume=64|issue=4|pages=741–46|doi=10.1093/jac/dkp274|pmc=2740635|pmid=19643775|vauthors=Smee DF, Hurst BL, Egawa H, Takahashi K, Kadota T, Furuta Y}}</ref> ''Hipoxantin guanin fosforibosiltransferase'' (HGPRT) diyakini memegang peran utama dalam proses metabolisme.<ref>{{Cite journal|date=Oktober 2013|title=Role of human hypoxanthine guanine phosphoribosyltransferase in activation of the antiviral agent T-705 (favipiravir)|journal=Molecular Pharmacology|volume=84|issue=4|pages=615–29|doi=10.1124/mol.113.087247|pmid=23907213|vauthors=Naesens L, Guddat LW, Keough DT, van Kuilenburg AB, Meijer J, Vande Voorde J, Balzarini J}}</ref> Favipiravir tidak menghambat sintesis RNA atau DNA dalam sel mamalia, sehingga tidak berbahaya bagi manusia.<ref name="Furuta">{{Cite journal|date=Juni 2009|title=T-705 (favipiravir) and related compounds: Novel broad-spectrum inhibitors of RNA viral infections|journal=Antiviral Research|volume=82|issue=3|pages=95–102|doi=10.1016/j.antiviral.2009.02.198|pmc=|pmid=19428599|vauthors=Furuta Y, Takahashi K, Shiraki K, Sakamoto K, Smee DF, Barnard DL, Gowen BB, Julander JG, Morrey JD}}</ref> Pada tahun 2014, favipiravir mendapat izin edar di Jepang untuk persediaan obat jika terjadi [[pandemi influenza]].<ref>{{Cite news|url=https://www.bloomberg.com/news/2014-08-07/ebola-drug-from-japan-may-emerge-among-key-candidates.html|title=Ebola Drug From Japan May Emerge Among Key Candidates|date=7 Agustus 2014|publisher=Bloomberg.com|first=Cynthia|last=Koons|access-date=2020-03-20|archive-date=2015-01-07|archive-url=https://web.archive.org/web/20150107180643/http://www.bloomberg.com/news/2014-08-07/ebola-drug-from-japan-may-emerge-among-key-candidates.html|dead-url=no}}</ref> Namun, favipiravir belum terbukti efektif pada sel di saluran pernapasan, sehingga terdapat keraguan mengenai efektivitas dalam pengobatan influenza.<ref>{{Cite journal|displayauthors=6|date=Agustus 2018|title=Orally Efficacious Broad-Spectrum Ribonucleoside Analog Inhibitor of Influenza and Respiratory Syncytial Viruses|journal=Antimicrobial Agents and Chemotherapy|volume=62|issue=8|pages=e00766–18|doi=10.1128/AAC.00766-18|pmc=6105843|pmid=29891600|vauthors=Yoon JJ, Toots M, Lee S, Lee ME, Ludeke B, Luczo JM, Ganti K, Cox RM, Sticher ZM, Edpuganti V, Mitchell DG, Lockwood MA, Kolykhalov AA, Greninger AL, Moore ML, Painter GR, Lowen AC, Tompkins SM, Fearns R, Natchus MG, Plemper RK}}</ref>

Pada tahun 2014, Jepang memberikan izin edar pada Favipiravir untuk mengobati virus yang tidak mempan terhadap antivirus yang ada saat ini.<ref>{{Cite journal|last=Hayden|first=Frederick|last2=|first2=|date=|title=Influenza virus polymerase inhibitors in clinical development|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6416007/|journal=[[Current Opinion in Infectious Diseases]]|volume=|issue=|pages=|doi=10.1097/QCO.0000000000000532|access-date=|archive-date=2023-04-29|archive-url=https://web.archive.org/web/20230429115155/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6416007/|dead-url=no}}</ref> Awalnya Toyama Chemical berharap bahwa Avigan akan menjadi obat influenza pengganti [[Tamiflu]]. Namun, percobaan pada hewan menunjukkan adanya efek [[teratogenik]] pada janin. Hal tersebut membuat pemberian izin edar oleh Kementerian Kesehatan Jepang tertunda lama. Selain itu, produksi obat ini hanya terbatas ketika terjadi keadaan darurat di Jepang. <ref>{{Cite web|url=https://diamond.jp/articles/-/49229|script-title=ja:条件付き承認で普及に足かせ 富山化学インフル薬の"無念"|access-date=20 Maret 2020|archive-date=2020-04-09|archive-url=https://web.archive.org/web/20200409095818/https://diamond.jp/articles/-/49229|dead-url=no}}</ref>

Pada Maret 2015, [[Badan Pengawas Obat dan Makanan Amerika Serikat|Badan Pengawas Obat dan Makanan AS]] telah meninjau hasil dari [[uji klinis]] fase III yang meneliti keamanan dan efektivitas Favipiravir dalam pengobatan influenza.<ref>{{Cite web|url=https://clinicaltrials.gov/ct2/show/results/NCT02026349|title=Phase 3 Efficacy and Safety Study of Favipiravir for Treatment of Uncomplicated Influenza in Adults - T705US316|last=|first=|date=|website=|publisher=[[FDA]]|access-date=20 Maret 2020|quote=|archive-date=2022-12-11|archive-url=https://web.archive.org/web/20221211124846/http://clinicaltrials.gov/ct2/show/results/NCT02026349|dead-url=no}}</ref>

Beberapa penelitian [[Organisme model|pada mencit]] menunjukkan bahwa Favipiravir mungkin efektif mwlawanmelawan [[Penyakit virus ebola|Ebola]]. Namun, obat ini tidak terbukti efektif melawan Ebola pada manusia.<ref name="Gatherer 2014">{{Cite journal|date=Agustus 2014|title=The 2014 Ebola virus disease outbreak in West Africa|journal=The Journal of General Virology|volume=95|issue=Pt 8|pages=1619–24|doi=10.1099/vir.0.067199-0|pmid=24795448|vauthors=Gatherer D}}</ref><ref>{{Cite journal|date=Mei 2014|title=Successful treatment of advanced Ebola virus infection with T-705 (favipiravir) in a small animal model|journal=Antiviral Research|volume=105|issue=|pages=17–21|doi=10.1016/j.antiviral.2014.02.014|pmid=24583123|vauthors=Oestereich L, Lüdtke A, Wurr S, Rieger T, Muñoz-Fontela C, Günther S}}</ref><ref>{{Cite journal|date=April 2014|title=Post-exposure efficacy of oral T-705 (Favipiravir) against inhalational Ebola virus infection in a mouse model|journal=Antiviral Research|volume=104|pages=153–55|doi=10.1016/j.antiviral.2014.01.012|pmid=24462697|vauthors=Smither SJ, Eastaugh LS, Steward JA, Nelson M, Lenk RP, Lever MS}}</ref> Selama [[Wabah virus Ebola di Afrika Barat|wabah virus Ebola di Afrika Barat tahun 2014]], terdapat laporan yang menyatakan seorang perawat [[Dokter Lintas Batas|MSF]] dari Prancis yang terkena Ebola di Liberia pulih setelah mendapat pengobatan dengan favipiravir.<ref>{{Cite news|title=First French Ebola patient leaves hospital|url=https://www.reuters.com/article/us-health-ebola-france-idUSKCN0HT0D720141004|work=Reuters|date=4 Oktober 2016|access-date=2020-03-20|archive-date=2020-02-19|archive-url=https://web.archive.org/web/20200219202526/https://www.reuters.com/article/us-health-ebola-france-idUSKCN0HT0D720141004|dead-url=no}}</ref> Pada Desember 2014, dilakukan uji klinis yang meneliti efektivitas favipiravir terhadap penyakit virus Ebola. Penelitian ini dimulai [[Guéckédougou|Guéckédou]], Guinea.<ref>{{Cite web|url=http://allafrica.com/stories/201412260651.html|title=Guinea: Clinical Trial for Potential Ebola Treatment Started in MSF Clinic in Guinea|publisher=AllAfrica – All the Time|access-date=20 Maret 2020|archive-date=2016-03-23|archive-url=https://web.archive.org/web/20160323201747/http://allafrica.com/stories/201412260651.html|dead-url=no}}</ref> Hasil awal menunjukkan penurunan tingkat kematian pada pasien Ebola dengan jumlah virus yang rendah-sedang dalam darah. Namun, Favipiravir tidak memiliki dampak yang signifikan pada pasien dengan jumlah virus yang tinggi.<ref>{{Cite news|url=https://www.nytimes.com/2015/02/05/science/ebola-drug-has-encouraging-early-results-and-questions-follow.html?smid=tw-share&_r=0|work=The New York Times|first=Sheri|last=Fink|title=Ebola Drug Aids Some in a Study in West Africa|date=4 Februari 2015|access-date=2020-03-20|archive-date=2020-03-18|archive-url=https://web.archive.org/web/20200318200541/https://www.nytimes.com/2015/02/05/science/ebola-drug-has-encouraging-early-results-and-questions-follow.html?smid=tw-share&_r=0|dead-url=no}}</ref> Desain penelitian ini dikritik oleh peneliti lainnya karena hanya menggunakan kontrol historis.<ref>{{Cite journal|last=Cohen|first=Jon|date=26 Februari 2015|title=Results from encouraging Ebola trial scrutinized|url=http://www.sciencemag.org/news/2015/02/results-encouraging-ebola-trial-scrutinized|journal=[[Science (journal)|Science]]|doi=10.1126/science.aaa7912|access-date=20 Maret 2020|archive-date=2020-02-19|archive-url=https://web.archive.org/web/20200219202546/https://www.sciencemag.org/news/2015/02/results-encouraging-ebola-trial-scrutinized|dead-url=no}}</ref>

== PenyakitUji viruscoba SARS-CoVuntuk COVID-219 ==

Pada uji coba dengan sampel subjek sebanyak 80 orang, Favipiravirfavipiravir memiliki aktivitas antivirus yang lebih kuat dibandingkan [[lopinavir/ritonavir]] dalam melawan [[SARS-CoV-2]] <ref>{{Cite journal|last=Dong|first=L|last2=Hu|first2=S|last3=Gao|first3=J|date=2020|title=Discovering drugs to treat coronavirus disease 2019 (COVID-19).|journal=Drug discoveries & therapeutics|volume=14|issue=1|pages=58-60|doi=10.5582/ddt.2020.01012|pmid=32147628}}</ref> Pada Maret 2020, pejabat pemerintah Tiongkok mengatakan bahwa Favipiravirfavipiravir efektif dalam mengobati penyakit koronavirus 2019. <ref name="Guardian 2020">{{Cite news|last=<!--Staff writer(s); no by-line.-->|date=2020-03-18|title=Japanese flu drug 'clearly effective' in treating coronavirus, says China|url=https://www.theguardian.com/world/2020/mar/18/japanese-flu-drug-clearly-effective-in-treating-coronavirus-says-china|work=The Guardian|access-date=20 Maret 2020|archive-date=2020-03-18|archive-url=https://web.archive.org/web/20200318200544/https://www.theguardian.com/world/2020/mar/18/japanese-flu-drug-clearly-effective-in-treating-coronavirus-says-china|dead-url=no}}</ref>