Phakathi nalolu bhubhane, odokotela basebenzisa amasosha omzimba ampontshelwa igazi (amasosha omzimba akhiqizwe elabhorethri) ukusiza iziguli ukulwa nokutheleleka nge-COVID-19. Manje abacwaningi be-UC Davis bazama ukwakha amasosha omzimba e-monoclonal angasiza ukulwa nobuhlungu obungapheli. Umgomo uwukuthuthukisa isidambisi sobuhlungu sanyanga zonke esingaluthisi esingangena esikhundleni se-opioid.
Le phrojekthi iholwa nguVladimir Yarov-Yarovoi noJames Trimmer, oprofesa eMnyangweni wePhysiology and Biology of Membrane eNyuvesi yaseCalifornia, eDavis School of Medicine. Bahlanganisa ithimba lezinhlaka eziningi elihlanganisa abacwaningi abaningi abafanayo ababezama ukuguqula ubuthi be-tarantula babe amaphilisi ezinhlungu.
Ngasekuqaleni kwalo nyaka, u-Yarov-Yarovoy kanye no-Trimmer bathola isibonelelo sika-$1.5 million ohlelweni lwe-HEAL lweNational Institutes of Health, okuwumzamo onolaka wokusheshisa izixazululo zesayensi zokuqukatha inkinga ye-opioid yezwe.
Ngenxa yobuhlungu obungapheli, abantu bangaba imilutha ye-opioid. ICenters for Disease Control's National Center for Health Statistics ilinganisela ukuthi kuzoba nabantu abangu-107,622 abashonile besebenzisa izidakamizwa e-United States ngo-2021, cishe ngama-15% ngaphezu kwabantu abalinganiselwa ku-93,655 abafa ngo-2020.
"Ukuphumelela kwakamuva kwe-biology yesakhiwo kanye ne-computational - ukusetshenziswa kwamakhompiyutha ukuze kuqondwe futhi kufane nezinhlelo zezinto eziphilayo - kuye kwabeka isisekelo sokusetshenziswa kwezindlela ezintsha zokudala amasosha omzimba njengabaqokelwe izidakamizwa ezinhle kakhulu zokwelapha ubuhlungu obungapheli," kusho u-Yarov. U-Yarovoy, umculi oyinhloko womklomelo we-Sai.
"Amasosha omzimba angama-Monoclonal ayindawo ekhula ngokushesha embonini yezemithi futhi anikeza izinzuzo eziningi kunezidakamizwa ze-molecule ezincane zakudala," kusho u-Trimmer. Izidakamizwa ze-molecule ezincane ziyizidakamizwa ezingena kalula kumaseli. Zisetshenziswa kakhulu kwezokwelapha.
Ngokuhamba kweminyaka, ilebhu ye-Trimmer idale izinkulungwane zamasosha omzimba ahlukene e-monoclonal ngezinjongo ezihlukahlukene, kodwa lona umzamo wokuqala wokwenza i-antibody eklanyelwe ukukhulula ubuhlungu.
Nakuba kubukeka kungokwekusasa, i-US Food and Drug Administration igunyaze amasosha omzimba e-monoclonal ekwelapheni nasekuvimbeleni i-migraine. Imithi emisha isebenza kuphrotheni ehambisana nemigraine ebizwa ngokuthi i-calcitonin peptide ehlobene nofuzo.
Iphrojekthi ye-UC Davis inomgomo ohlukile - iziteshi ze-ion eziqondile kumaseli ezinzwa ezibizwa ngokuthi iziteshi ze-sodium ezine-voltage-gated. Lezi ziteshi zifana “nezimbotshana” kumangqamuzana ezinzwa.
“Amangqamuzana emizwa anesibopho sokudlulisa izimpawu zobuhlungu emzimbeni. Iziteshi ze-sodium ion ezingase zibe khona emangqamuzaneni ezinzwa zingabadlulisi abakhulu bobuhlungu,” kuchaza u-Yarov-Yarovoy. "Umgomo wethu uwukwenza amasosha omzimba abopha lezi zindawo zokudlulisela okuthile ezingeni lamangqamuzana, avimbele umsebenzi wawo futhi avimbele ukudluliswa kwezimpawu zobuhlungu."
Abacwaningi bagxile eziteshini ezintathu ze-sodium ezihlotshaniswa nobuhlungu: i-NaV1.7, i-NaV1.8, ne-NaV1.9.
Umgomo wabo uwukwakha amasosha omzimba afana nalawa mashaneli, njengokhiye ovula ingidi. Le ndlela ehlosiwe iklanyelwe ukuvimba ukudluliswa kwezimpawu zobuhlungu ngesiteshi ngaphandle kokuphazamisa ezinye izimpawu ezidluliselwa ngamangqamuzana ezinzwa.
Inkinga ukuthi ukwakheka kweziteshi ezintathu abazama ukuzivimba kuyinkimbinkimbi kakhulu.
Ukuxazulula le nkinga, baphendukela ezinhlelweni ze-Rosetta ne-AlphaFold. Nge-Rosetta, abacwaningi bakha amamodeli amaprotheni abonakalayo ayinkimbinkimbi futhi bahlaziya ukuthi imaphi amamodeli afaneleka kangcono iziteshi ze-neural ze-NaV1.7, NaV1.8, ne-NaV1.9. Nge-AlphaFold, abacwaningi bangahlola ngokuzimela amaprotheni akhiwe yi-Rosetta.
Lapho sebehlonze amaprotheni ambalwa athembisayo, bakha amasosha omzimba ayengase ahlolwe ezicutshini ze-neural ezakhiwe elebhu. Izilingo zabantu zizothatha iminyaka.
Kodwa abacwaningi bajabule ngamandla ale ndlela entsha. Izidakamizwa ezingekho-steroidal eziqeda ukuvuvukala (ama-NSAID), njenge-ibuprofen ne-acetaminophen, kufanele ziphuzwe izikhathi eziningana ngosuku ukuze kudambise ubuhlungu. Amaphilisi ezinhlungu e-opioid ngokuvamile athathwa nsuku zonke futhi anengozi yokulutheka.
Kodwa-ke, amasosha omzimba angama-monoclonal angajikeleza egazini isikhathi esingaphezu kwenyanga ngaphambi kokuba ahlukaniswe umzimba ekugcineni. Abacwaningi babelindele ukuthi iziguli zizinikeze ngokwazo i-analgesic monoclonal antibody kanye ngenyanga.
"Ezigulini ezinobuhlungu obungapheli, yilokhu kanye okudingayo," kusho u-Yarov-Yarovoy. “Abazwa izinhlungu izinsuku, kodwa amasonto nezinyanga. Kulindeleke ukuthi amasosha omzimba ajikelezayo akwazi ukuhlinzeka ngokukhululeka kobuhlungu okuhlala amasonto ambalwa.”
Amanye amalungu eqembu ahlanganisa uBruno Correia we-EPFL, uSteven Waxman we-Yale, uWilliam Schmidt we-EicOsis noHeike Wolf, uBruce Hammock, uTeanne Griffith, uKaren Wagner, uJohn T. Sack, uDavid J. Copenhaver, uScott Fishman, uDaniel J. Tancredi, u-Hai Nguyen, Phuong Tran Nguyen, Diego Lopez Mateos, noRobert Stewart we-UC Davis.
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Isikhathi sokuthumela: Sep-29-2022