Hinokitiol: Versiyalar orasidagi farq

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3-Iyul 2020, 04:40 dagi koʻrinishi

Andoza:Infobox chemische stof Xinokitiol (β-tuaplisin) - Kiparis oilasidagi daraxtlar yog'ochidan topilgan tabiiy monoterpenoiddir. Bu tropolonning hosilasi va tuyaplitsinlardan biridir. Xinokitiol og'izni parvarish qilish mahsulotlarida keng qo'llaniladi va keng spektrli antimikrobiyal va yallig'lanishga qarshi faollikka ega. Bundan tashqari, Yaponiyada oziq-ovqat mahsulotlarini saqlashga yordam beruvchi oziq-ovqat qo'shimchasi sifatida tasdiqlangan.[1][2][3][4][5]

"Xinokitiol" nomi 1936-yilda dastlab Tayvan xinokisidan ajratib olinganligi bilan bog'liqdir. U yapon xinokilarida deyarli yo'q bo’lib, anyi vaqtda mojjevelnik (archa) yog’ochida, xiba kedr (sadr) yog’ochi va gigant tuya yog’ochlarida yuqori kansentratsiyani o’z ichiga oladi (yog'och massasining yadrosining o’g’irligi 0,04% atrofida).[6] Uni kedr (sadr) yog'ochidan erituvchi va ultratovush yordamida osongina olish mumkin.[7]

Xinokitiol tizimli ravishda tropolon bilan bog'liq bo'lib, unda izopropil o'rinbosari yo'qdir. Tropolonlar xelatlash agentlari (vositalari) sifatida tanilgan.

Mikroblarga qarshi faolliklari

Xinokitiol biologik faollikning keng doirasiga ega bo’lib, ularning aksariyati adabiyotlarda o'rganilgan va tasvirlangan. Birinchi va eng yaxshi ma'lum bo'lgani, bu uning antibiotiklarga chidamliligidan qaramasdan ko'plab bakteriyalar va zamburug'larga qarshi hamda kuchli mikroblarga qarshi faollik ko'rsatishidir. Xususan, xinokitiol Streptococcus pneumoniae, Streptococcus mutans va Staphylococcus Aureus, umumiy inson patogenlariga qarshi samaradorlikni namoyish etadi. Bundan tashqari, xinokitiolning Chlamydia trachomatisga qarshi kamaytirish ta'siriga ega ekanligi va mahalliy dori vositasi sifatida klinik jihatdan foydali bo'lishi mumkinligi isbotlangan. Keyinchalik tadqiqotlar shuni ko'rsatdiki, xinokitiol shuningdek, rinovirus, koksaki virusi va mengovirus virusini o'z ichiga olgan bir nechta inson viruslariga qarshi sink (rux) birikmasi bilan birgalikda ishlatilganda antiviral faollikni namoyish etadi.[8][9] [10] [11] [12] [13]

Antiviral faollik

So'nggi yillarda o'tkazilgan tadqiqotlar shuni ko'rsatadiki, Hinokitiol odamning turli viruslariga, shu jumladan rinovirus, koksakskievirus va mengovirusga qarshi rux aralashmasi bilan birgalikda ishlatilganda antiviral ta'sir ko'rsatadi. [14] Virusli infektsiyalarni davolash katta iqtisodiy foyda keltirishi mumkin va Jahon sog'liqni saqlash tashkiloti kabi global institutlar uchun katta ahamiyatga ega bo'lishi kerak. Virusli qayta ishlash cheklash poliproteini, Hinokitiol inhibe Virusli ko'payish - Hinokitiol bir chunki Biroq, bu qobiliyati, ikki, qimmatbaho metall ionlarining mavjudligi bog'liq tuzining uning. [15] Sinkning Xinokitiol bilan birgalikda mavjudligi ushbu variantlarni qo'llab-quvvatlaydi va quyida muhokama qilinadi.

Boshqa faolliklari

Keng spektrli antimikrobiyal faoliyatdan tashqari, xinokitiol in vitro hujayra tadqiqotlari va in vivo jonli hayvonlarni tadqiq qilishda tasvirlangan yallig'lanishga qarshi va antikanser faoliyatga ega. Kinokitiol TNF-a va NF-kB kabi asosiy belgilar va yallig'lanish yo'llarini kamaytiradi. Surunkali yallig'lanish yoki autoimmun sharoitlarda davolash uchun uning salohiyati ham o'rganilmoqda. Aniqlandiki, xinokitiol bir necha ma'lum saraton hujayralariga sitotoksik ta'sir ko'rsatadi, bu esa autofagik jarayonlarga olib keladi.[16] [17]

Koronavirus tadqiqotlari

Hinokitiolning viruslarga qarshi ta'siri uning sink (rux) ionofori ta'siridan kelib chiqadi. Xinokitiol RNK viruslarining replikatsiya mexanizmini kamaytiruvchi va buning oqibatida, virus replikatsiyasini kamaytiruvchi hujayralarga sink (rux) ionlari oqimini ta'minlaydi.  Ma'lum bo'lgan RNK viruslariga inson grippi virusi, SARS va yangi paydo bo'lgan koronavirus kiradi. Tadqiqot yangi paydo bo'lgan koronavirus bilan juda ko'p o'xshash bo'lgan yana bir koronavirus bo'lgan SARS ning replikatsiyasini inhibe qilishda sink ionofor bilan sink (rux) ionlarining samaradorligini tasdiqladi. Sink (rux) ionlari virusning hujayralar ichidagi replikatsiyasini sezilarli darajada kamaytirishi mumkinligi aniqlandi va faolligi sink oqimiga bog'liq ekanligi isbotlandi. Ushbu tadqiqot sink (rux) ionafor pirition bilan amalga oshirildi, uning ishlashi xinokitiolning ishlashiga juda o'xshashdir. [14] [18]

Hujayra kulturalarida hinokitiol inson rinovirusi, koksakskievirus va mengovirusning ko'payishini inhibe qiladi. Hinokitiol pikornavirusning ko'payishini inhibe qiladigan virusli polipoteinlarni qayta ishlashga xalaqit beradi. Xinokitiol pikornaviruslarning replikatsiyasini virusli polipoteinlarni qayta ishlashini susaytiradi va hinokitiolning antiviral faolligi sink ionlarining mavjudligiga bog'liq. [19]

Temir ionofori

Xinokitiol kemiruvchilarda gemoglobin ishlab chiqarishni tiklash uchun ko'rsatildi. Xinokitiol hujayra ichidagi temir darajasini oshirib, temirni hujayralarga yo'naltirish uchun temir ionofori vazifasini bajaradi. Odamlarda temirning taxminan 70% qizil qon hujayralari va xususan gemoglobin oqsili tarkibida bo'ladi. Temir deyarli barcha tirik organizmlar uchun juda muhimdir va kislorod transport tizimi, deoksiribonuklein kislotasi (DNK) sintezi va elektron transport va temir tanqisligi kabi bir nechta anatomik funktsiyalarning muhim elementi anemiya kabi qon kasalliklariga olib kelishi mumkin, bu ham jismoniy, ham aqliy ishlashga sezilarli darajada zarar yetkazishi mumkin.[20] [21] [22]

Rux sinergizmi

Xinokitiol sink ionoforidir va bu qobiliyat viruslarning replikatsiyasini kamaytiradi. Qisqacha aytganda, sink (rux) ionofori kabi, xinokitiol molekulalarni hujayralarga plazma membranasi yoki hujayra ichidagi membrana orqali tashishda yordam beradi va shu bilan belgilangan molekulaning hujayra ichidagi kontsentratsiyasini oshiradi. Binobarin, sink (rux)ning antivirus xususiyatlarini Xinokitiol bilan birgalikda qo'llash orqali sinkning yemilishini tezlashtirish mumkin.[23]

Saraton tadqiqotlari

Hujayra madaniyati va hayvon tadqiqotlarida kinokitiolning metatezni kamaytirganligi [24] [25] va saraton hujayralariga antiproliferativ ta'sir ko'rsatganligi ko'rsatildi.[26] [27] [28] [29] [30] [31]

Sink (rux) yetishmasligi

Sink (rux) yetishmovchiligi ba'zi saraton hujayralarida namoyon bo'ldi va optimal hujayra ichidagi sink (rux) darajasini qaytarish o'simta o'sishini bostirishga olib kelishi mumkin. Xinokitiol hujjatlashtirilgan sink ruh ionoforidir, ammo hozirgi vaqtda Xinokitiol va sink (rux)ni yetkazib berish usullarining samarali kontsentratsiyasini aniqlash uchun qo'shimcha tadqiqotlar talab etiladi.

  • "Melanoma o'sishi va eksperimental metastaz oziq-ovqat rux ta'siri..." [32]
  • "Rux parhez taqchilligi qizilo'ngach saratoni rivojlanishini oziqlantirib, alohida yallig'lanish belgisini sabablari..." [33]
  • Sarum sink darajasi va o'pka saratoni o'rtasidagi bog'liqlik: kuzatish ishlarining meta-tahlillari..."[34]
  • "Rux tanqisligi bilan bog'liq microRNAs s va qizilo'ngach saratoni o'rtasidagi munosabatlarni o'rganish taraqqiyot..."[35]

Xinokitiolni o'z ichiga olgan mahsulotlar

EWG balli shkalasi

Xinokitiol kosmetika, tish pastasi, og'iz spreyi, quyosh kremi va soch o'sishi mahsulotlarini o'z ichiga olgan bir qator iste'mol mahsulotlarida keng qo'llaniladi. Xinokitiol iste'mol mahsulotlarini sotishda yetakchi brendlardan biri Hinoki Clinical hisoblanadi. Hinoki Clinical (1956) 1955da birinchi "kinokitiolni sanoat ishlab chiqarish"boshlanganidan ko'p o'tmay tashkil etilgan[36]. Boshqa bir brend, ya'ni "Relief Life",[37] xinokitiolni o'z ichiga olgan "Dental Series" tish pastasida milliondan ortiq sotuvlar bilan faxrlanadi.[38] Boshqa mashhur kinokitiol mahsulotlari ishlab chiqaruvchilari orasida Otsuka Pharmaceuticals, Kobayashi Pharmaceuticals, Taisho Pharmaceuticals, SS Pharmaceuticals mavjud. Osiyodan tashqari, Swanson Vitamins ® kabi kompaniyalar AQSh[39] va Avstraliya [40] kabi bozorlarda antioksidant zardob va boshqa harakatlarda iste'mol mahsulotlarida xinokitioldan foydalanishni boshlaydilar. 2006 yilda xinokitiol Kanadadagi moddalarning milliy ro'yxatiga ko'ra suv organizmlari uchun beqaror, bioakkumulyatsiyalanmagan va toksik bo'lmagan deb tasniflangan.[41]

Ekologik ishchi guruhi (EWG), Amerika faollar guruhi, sahifani xinokitiol tarkibiga bag'ishladi, bu "allergiya va immunotoksiklik", "saraton" va "rivojlanish va reproduktiv toksiklik" kabi sohalarda "past xavfli" ekanligini ko'rsatib, Xinokitiolga 1-2 bahosini berdi. Propilparaben (xinokitiolni baholashdan farqli o'laroq) turli xil og'iz yuvish vositalarida hali ham sotiladigan tarkibiy qism katta toksiklik va xavfli muammolarni keltirib chiqaradi. Propilparaben Evropa gormonlarni buzish komissiyasi tomonidan boshqa muammolar qatorida insonning endokrin buzuvchisi sifatida e'tirof etildi va uni EWG veb-saytida 4-6 bal darajasida qoldirildi. [42] [43]

Dr ZinX

2020-yil 2-aprelda Avstraliyaning Advance Nanotek[44] rux oksidi ishlab chiqaruvchi korxonasi muhim tarkibiy qismi sifatida o'z ichiga olgan xinokitiolni turli og'iz parvarishlash mahsulotlari, shu jumladan, virusga qarshi tarkibi uchun AstiVita Limited bilan qo'shma patent ariza topshirdi[45]. Ushbu yangi ixtironi o'z ichiga olgan brend doktor ZinX deb ataladi va ehtimol 2020-yilda sink(rux) + Xinokitiolning kombinatsiyasini chiqaradi. Doktor ZinX 2020-yil 18-mayda "tibbiy sohadagi virusli faollikni baholash uchun miqdordagi suspenziya sinovi" natijalarini e'lon qildi. Natijada surrogat mushuk koronavirusi COVID-19ga qarshi 5 daqiqa davomida "3,25 log" (99,9%) toza konsentratsiyaga kamaygan. Sink (rux) tananing ajralmas oziq-ovqat mahsuloti va mikroelementidir. Jahon sog'liqni saqlash tashkiloti hisob-kitoblariga ko'ra, aholining 17,3% sink (rux) iste'moli kam. [46] [47] [48] [49] [50] [51] [52] [53]

Tarix

Kashf etilishi

Xinokitiol - 1936-yilda Tetsuo Nozoe tomonidan Tayvan kiparisi efir moyidan doktor kashf etilgan. Tabiatda mavjud emasligi aytilgan geptagonal molekulyar tuzilishga ega bo'lgan bu birikmaning kashf etilishi global miqyosda kimyo tarixida katta yutuq sifatida e'tirof etildi. [54]

Nozoe Tetsuo

Nozoe Tetsuo 16-may 1902-yil Yaponiya Sendai shahrida tug'ilgan. U 21 yoshida Tohoku Imperial universitetining kimyo fakultetiga o'qishga kirdi.1926 yil mart oyida universitetni tugatgach, Nozoe ilmiy xodim bo'lib qoldi. Lekin tez orada Sendai shahrini tark etdi va 1926 yil iyun oyining oxirida Formoz (hozirgi Tayvan nomi bilan tanilgan) ga ko'chib o'tdi.[55] [56]

Nozoening asosiy ilmiy manfaatlari tabiiy mahsulotlarni, ayniqsa Formozda mavjud bo'lganlarini o'rganish bilan bog'liq. Nozoening Formozdagi hujjatlashtirilgan ishi tog'li hududlarda o'sadigan mahalliy ignabargli tosh Tayvanxinokaning kimyoviy tarkibiy qismlari bilan bog'liq. Nozoe bu turning tarkibiy qismlaridan yangi birikma, xinokitiolni aniqladi va bu haqda birinchi marta 1936-yilda Yaponiyaning kimyoviy jamiyati byulletenining maxsus sonida ma'lum qildi.

[57] [58]

1950 yil noyabr oyida London kimyoviy jamiyati tomonidan "Tropolon va ittifoqdosh birikmalar" simpoziumi tashkil etilganda, Nozoe-ning hinokitiol bo'yicha faoliyati tropolon kimyosining kashshof hissasi sifatida tilga olinadi va shu bilan Nozoe tadqiqotlari G'arbda tan olinishiga yordam beradi.[59] Nozoe 1951 yilda J.W. tufayli hinokitiol va uning hosilalarini tabiatda nashr etishga muvaffaq bo'ldi. Kuk, simpozium raisi. Tayvanda tabiiy mahsulotlarni tadqiq qilish bilan boshlangan va 1950 va 60-yillarda Yaponiyada to'liq ishlab chiqilgan Nozoe ishi organik kimyoning yangi sohasini, ya'ni benzenoid bo'lmagan aromatik birikmalar kimyosini joriy qildi. [60] Uning ishi Yaponiyada yaxshi qabul qilindi va shu sababli Nozoe 1958 yilda 56 yoshida tadqiqotchilar va rassomlarga qo'shgan hissasi uchun eng yuqori sharaf bo'lgan Madaniyat ordeni bilan taqdirlandi. [61]

Istiqbolli Kelajak

2000-yillardan boshlab (xususan Chlamydia trachomatis bakteriyasini kamaytirish uchun) tadqiqotchilar xinokitiolni farmatsevtika sifatida qadrlashlari mumkinligini tan olishdi.

Kimyogar Martin Burke va Urbana-Champaigndagi Illinoys universitetidagi hamkasblar xinokitiolning muhim tibbiy maqsadlarini aniqladilar. Burkning maqsadi temirni hayvonlar tomonidan muntazam ravishda olib o'tishni yengish edi. Bir nechta oqsil etishmasligi hujayralardagi temir tanqisligiga (anemiya) yoki teskari ta'sir - gemoxromatozga olib kelishi mumkin edi. Genropatiyasi pasaygan xamirturush kultivatsiyasidan surrogat sifatida foydalanib, tadqiqotchilar temir transporti va shuning uchun hujayra o'sishi belgilari uchun kichik biomolekulalar kutubxonasini tekshirdilar. Xinokitiol hujayralarning funksionalligini tiklaydigan vosita sifatida paydo bo'ldi. Jamoa tomonidan olib borilgan keyingi ishlarda xinokitiol hujayra temirini tiklaydigan yoki kamaytiradigan mexanizm yaratildi. Keyin ular tadqiqotlarini sutemizuvchilarga o'tkazishdi va kemiruvchilar "temir oqsillari" etishmasligi uchun xinokitiol olganlarida, ichakdagi temirning so'rilishini tikladilar. Zebra balig'idagi shunga o'xshash tadqiqotda molekula gemoglobin ishlab chiqarishni tikladi. Burke ishiga berilgan sharh "Temir odam molekulasi" deb nom oldi. Bu to’g’ri va o’rinli edi, chunki Nozoe kashfiyotchisining ismi ingliz tiliga "Temir odam" deb tarjima qilinishi mumkin. [62] [63] [64]

Xinokitiolni og'iz orqali yuborish sohasida ham muhim tadqiqotlar olib borilgan, chunki hinokitiol asosidagi og'iz mahsulotlariga talab ortib borgan. Yaponiyadagi 8 ta turli institutlar bilan birgalikda olib borilgan shunday tadqiqotlar: «Hinokitiolning antitakteriyaga chidamli va ular uchun sezgir bo'lgan patogen bakteriyalarga nisbatan og'iz bo'shlig'i va yuqori nafas yo'llarida ustunlik qiladi», degan xulosaga keldi. "xinokitiol turli xil patogen bakteriyalarga qarshi antibakterial ta'sir ko'rsatadi va inson epitelial hujayralariga nisbatan past sitotoksiklikka ega".[11] [64]

Tegishli tadqiqotlar

  • "Zn2 + koronavirus va arterivirus RNK polimeraza faolligini kamaytiradi in vitro va rux ionoforalari bu viruslarning hujayra madaniyatidagi replikatsiyasini to'sadi..." [18]
  • "Pikornavirus infeksiyalariga qarshi rux Ionoforalari Pirition va Xinokitiolning Antiviral faolligi..."[65]
  • "Erta tashxis tomoq yuvish va so'lak SARS bog'liq koronavirus aniqlash..."[66]
  • "Og'iz shilliq qavatining epitelial hujayralari haqida 2019-nCoV ACE2 retseptorlari yuqori ifodasi..."[67]
  • "Antiviral Dori..."
  • "Antiviral vosita va tomoqdan tayyorlangan shakarlama(ledinitsa)lar, tomoq chayish va og'iz yuvish vositasi ..."
  • "Antibakterial va antifungal faoliyat usuli, yuqumli kasalliklarning terapevtik usuli va kosmetika vositalarini konservalash usuli..."[68]
  • "Sinokitiolning sichqonlardagi eksperimental ligaturaga bog'liq periodontitda periodontal suyak yo'qolishiga qarshi himoya ta'siri...”[69]
  • "Yangi antidiyabetik rux (II) - ZN (O4) muvofiqlashtirish rejimiga ega bo'lgan Xinokitiol (β-Tucaplicin) kompleksi ..."[70]
  • "[Zn(hkt)2] (sink & Hinokitiol) insulin qarshiligini amelioratsiyalash yo'li bilan periferik organlarga asosiy ta'sirni kuchaytirilishi..."[71]

Adabiyotlar

  1. ↑ "Effects of leaching on fungal growth and decay of western redcedar". Canadian Journal of Microbiology 55 (5): 578–86. May 2009. doi:10.1139/W08-161. PMID 19483786. 
  2. ↑ "Antiviral activity of the zinc ionophores pyrithione and hinokitiol against picornavirus infections". Journal of Virology 83 (1): 58–64. January 2009. doi:10.1128/JVI.01543-08. PMID 18922875. PMC 2612303. https://pubmed.ncbi.nlm.nih.gov/18922875/. 
  3. ↑ "Antimicrobial activity and metalloprotease inhibition of hinokitiol-related compounds, the constituents of Thujopsis dolabrata S. and Z. hondai MAK". Biological & Pharmaceutical Bulletin 22 (9): 990–3. September 1999. doi:10.1248/bpb.22.990. PMID 10513629. https://pubmed.ncbi.nlm.nih.gov/10513629/. 
  4. ↑ "Anti-inflammatory effects of hinokitiol on human corneal epithelial cells: an in vitro study". Eye 29 (7): 964–71. July 2015. doi:10.1038/eye.2015.62. PMID 25952949. PMC 4506343. https://pubmed.ncbi.nlm.nih.gov/25952949/. 
  5. ↑ "Stress Check System". Health evaluation and promotion 43 (2): 299–303. 2016. doi:10.7143/jhep.43.299. ISSN 1347-0086. http://dx.doi.org/10.7143/jhep.43.299. 
  6. ↑ "Tetsuo Nozoe: chemistry and life". Chemical Record 12 (6): 599–607. December 2012. doi:10.1002/tcr.201200024. PMID 23242794. 
  7. ↑ "Screening fungi tolerant to Western red cedar (Thuja plicata Donn) extractives. Part 1. Mild extraction by ultrasonication and quantification of extractives by reverse-phase HPLC". Holzforschung 61 (2): 190–194. 2007. doi:10.1515/HF.2007.033. 
  8. ↑ "In vitro antimicrobial and anticancer potential of hinokitiol against oral pathogens and oral cancer cell lines". Microbiological Research 168 (5): 254–62. June 2013. doi:10.1016/j.micres.2012.12.007. PMID 23312825. 
  9. ↑ "The mechanism of the bactericidal activity of hinokitiol". Biocontrol Science 12 (3): 101–10. September 2007. doi:10.4265/bio.12.101. PMID 17927050. 
  10. ↑ "Evaluation of the Antibacterial Potential of Liquid and Vapor Phase Phenolic Essential Oil Compounds against Oral Microorganisms". PloS One 11 (9): e0163147. 2016-09-28. doi:10.1371/journal.pone.0163147. PMID 27681039. PMC 5040402. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5040402. 
  11. ↑ 11,0 11,1 "Antibacterial activity of hinokitiol against both antibiotic-resistant and -susceptible pathogenic bacteria that predominate in the oral cavity and upper airways". Microbiology and Immunology 63 (6): 213–222. June 2019. doi:10.1111/1348-0421.12688. PMID 31106894. 
  12. ↑ "In vitro inhibitory effects of hinokitiol on proliferation of Chlamydia trachomatis". Antimicrobial Agents and Chemotherapy 49 (6): 2519–21. June 2005. doi:10.1128/AAC.49.6.2519-2521.2005. PMID 15917561. PMC 1140513. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1140513. 
  13. ↑ Chedgy. Secondary metabolites of Western red cedar (Thuja plicata): their biotechnological applications and role in conferring natural durability.. LAP Lambert Academic Publishing, 2010. ISBN 978-3-8383-4661-8. 
  14. ↑ 14,0 14,1 "Antiviral activity of the zinc ionophores pyrithione and hinokitiol against picornavirus infections". Journal of Virology 83 (1): 58–64. January 2009. doi:10.1128/JVI.01543-08. PMID 18922875. PMC 2612303. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2612303. 
  15. ↑ Krenn, B. M. (January 2009). "Antiviral Activity of the Zinc Ionophores Pyrithione and Hinokitiol against Picornavirus Infections". Journal of Virology 83 (1): 58–64. doi:10.1128/JVI.01543-08. ISSN 0022-538X. PMID 18922875. PMC 2612303. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2612303/. 
  16. ↑ "Can Hinokitiol Kill Cancer Cells? Alternative Therapeutic Anticancer Agent via Autophagy and Apoptosis" (en). Korean Journal of Clinical Laboratory Science 51 (2): 221–234. 2019-06-30. doi:10.15324/kjcls.2019.51.2.221. 
  17. ↑ "Hinokitiol Inhibits Migration of A549 Lung Cancer Cells via Suppression of MMPs and Induction of Antioxidant Enzymes and Apoptosis". International Journal of Molecular Sciences 19 (4): 939. March 2018. doi:10.3390/ijms19040939. PMID 29565268. PMC 5979393. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5979393. 
  18. ↑ 18,0 18,1 "Zn(2+) inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture". PLoS Pathogens 6 (11): e1001176. November 2010. doi:10.1371/journal.ppat.1001176. PMID 21079686. PMC 2973827. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2973827. 
  19. ↑ "Antiviral activity of the zinc ionophores pyrithione and hinokitiol against picornavirus infections". Journal of Virology 83 (1): 58–64. January 2009. doi:10.1128/jvi.01543-08. PMID 18922875. PMC 2612303. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2612303. 
  20. ↑ "Restored iron transport by a small molecule promotes absorption and hemoglobinization in animals". Science 356 (6338): 608–616. May 2017. doi:10.1126/science.aah3862. PMID 28495746. PMC 5470741. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5470741. 
  21. ↑ Service, Robert F. (2017-05-11). "Iron Man molecule restores balance to cells". Science (AAAS). doi:10.1126/science.aal1178. 
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