Ngexesha lo bhubhani, oogqirha basebenzisa ii-antibodies ze-monoclonal (i-laboratory-produced antibodies) ukunceda abaguli ukulwa usulelo lwe-COVID-19. Ngoku abaphandi be-UC Davis bazama ukwenza ii-antibodies ze-monoclonal ezinokunceda ukulwa nentlungu engapheliyo. Injongo kukuphuhlisa isithomalalisi seentlungu zenyanga esingakhobokiyo esinokuthatha indawo ye-opioids.
Le projekthi ikhokelwa nguVladimir Yarov-Yarovoi kunye noJames Trimmer, oonjingalwazi kwiSebe lePhysiology kunye neBiology yeMembrane kwiYunivesithi yaseCalifornia, iDavis School of Medicine. Bahlanganisa iqela lezinto ezininzi ezibandakanya abaninzi abaphandi abafanayo ababezama ukuguqula i-tarantula venom ibe yi-painkillers.
Ekuqaleni kwalo nyaka, u-Yarov-Yarovoy kunye no-Trimmer bafumana isibonelelo se-1.5 yezigidi zeedola kwiNkqubo yeSizwe yezeMpilo ye-HEAL, inzame enobudlova yokukhawulezisa izisombululo zenzululwazi ukuze ziqulethe ingxaki ye-opioid yelizwe.
Ngenxa yeentlungu ezingapheliyo, abantu banokuba likhoboka le-opioids. Iziko leSizwe loLawulo lweSifo leZiko leSizwe leNkcazo yezeMpilo liqikelela ukuba kuya kubakho ukusweleka kweziyobisi ezingama-107,622 e-United States ngo-2021, phantse i-15% ngaphezulu kokusweleka okuqikelelwa kwe-93,655 ngo-2020.
"Ukuphumelela kwangoku kwi-biology ye-structural and computational biology - ukusetyenziswa kweekhomputha ukuqonda kunye nomzekelo weenkqubo ze-biological - ubeke isiseko sokusetyenziswa kweendlela ezintsha zokudala ama-antibodies njengabaviwa abagqwesileyo beziyobisi ukunyanga ubuhlungu obungapheliyo," kusho uYarov. UYarovoy, oyena mdlali uphambili wembasa yeSai.
"Ii-antibodies ze-Monoclonal yeyona ndawo ikhula ngokukhawuleza kwishishini lamayeza kwaye ibonelela ngeenzuzo ezininzi kumachiza amancinci aqhelekileyo," utshilo u-Trimmer. Amachiza emolekyuli amancinci ngamachiza angena lula kwiiseli. Zisetyenziswa kakhulu kwezamayeza.
Ukutyhubela iminyaka, ilebhu ye-Trimmer yenze amawaka ee-antibodies ezahlukeneyo ze-monoclonal ngeenjongo ezahlukeneyo, kodwa lo ngumzamo wokuqala wokudala i-antibody eyenzelwe ukuthomalalisa iintlungu.
Nangona kubonakala ngathi i-futuristic, i-US Food and Drug Administration ivume ii-antibodies ze-monoclonal kunyango kunye nokuthintela i-migraine. Amachiza amatsha asebenza kwiprotheyini ehambelana ne-migraine ebizwa ngokuba yi-calcitonin ye-peptide enxulumene nofuzo.
Iprojekthi ye-UC Davis inenjongo eyahlukileyo - iziteshi ze-ion ezithile kwiiseli ze-nerve ezibizwa ngokuba yi-voltage-gated sodium channels. Le mijelo ifana “nemingxuma” kwiiseli zemithambo-luvo.
“Iiseli zemithambo-luvo zinoxanduva lokuhambisa iimpawu zentlungu emzimbeni. Iziteshi ze-ion ze-sodium ezinokubakho kwiiseli zemithambo-luvo zizona zithutha iintlungu eziphambili, utshilo uYarov-Yarovoy. "Injongo yethu kukudala i-antibodies ebophelela kwezi ndawo zokudluliselwa kwinqanaba le-molecular, inqanda umsebenzi wabo kwaye ivimbele ukuhanjiswa kweempawu zentlungu."
Abaphandi bagxininise kwiitshaneli ezintathu ze-sodium ezihambelana nentlungu: i-NaV1.7, i-NaV1.8, kunye ne-NaV1.9.
Injongo yabo kukwenza amajoni omzimba ahambelana nezi jelo, njengesitshixo esivula isitshixo. Le ndlela ekujoliswe kuyo yenzelwe ukuthintela ukuhanjiswa kweempawu zentlungu ngokusebenzisa umjelo ngaphandle kokuphazamisana nezinye iimpawu ezithunyelwa ngeeseli ze-nerve.
Ingxaki kukuba isakhiwo semijelo emithathu abazama ukuyivimba sinzima kakhulu.
Ukusombulula le ngxaki, baphendukela kwiinkqubo zeRosetta kunye neAlphaFold. NgeRosetta, abaphandi baphuhlisa iimodeli ezintsonkothileyo zeprotheyini kunye nokuhlalutya ukuba yeyiphi imodeli efanelekileyo kakhulu kwi-NaV1.7, NaV1.8, kunye ne-NaV1.9 ye-neural channels. Nge-AlphaFold, abaphandi banokuvavanya ngokuzimeleyo iiprotheni eziphuhliswe nguRosetta.
Nje ukuba bachonge iiproteni ezimbalwa ezithembisayo, baye benza ii-antibodies ezinokuthi emva koko zivavanywe kwii-neural tissue ezenziwe kwilebhu. Ulingo lwabantu luya kuthatha iminyaka.
Kodwa abaphandi banochulumanco ngokubakho kwale ndlela intsha. Iziyobisi ezingekho steroidal ezichasene nokudumba (NSAIDs), ezifana ne-ibuprofen kunye ne-acetaminophen, kufuneka zithathwe amaxesha amaninzi ngemini ukukhulula iintlungu. I-opioid painkillers idla ngokuthathwa yonke imihla kwaye inomngcipheko wokuba likhoboka.
Nangona kunjalo, ii-antibodies ze-monoclonal zinokujikeleza egazini ixesha elingaphezu kwenyanga ngaphambi kokuba ekugqibeleni ziphulwe ngumzimba. Abaphandi balindele ukuba izigulana zizenzele ngokwazo i-analgesic monoclonal antibody kanye ngenyanga.
"Kubaguli abaneentlungu ezingapheliyo, yile nto kanye oyifunayo," utshilo uYarov-Yarovoy. Baziva iintlungu kungekhona iintsuku, kodwa iiveki neenyanga. Kulindeleke ukuba amajoni omzimba ajikelezayo akwazi ukunika isiqabu kwiintlungu ezihlala iiveki ezininzi. ”
Amanye amalungu eqela aquka i-EPFL kaBruno Correia, uSteven Waxman kaYale, u-EicOsis 'uWilliam Schmidt noHeike Wolf, uBruce Hammock, uTeanne Griffith, uKaren Wagner, uJohn T. Sack, uDavid J. Copenhaver, uScott Fishman, uDaniel J. Tancredi, uHai Nguyen, Phuong Tran Nguyen, Diego Lopez Mateos, kunye noRobert Stewart we-UC Davis.
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Ixesha lokuposa: Sep-29-2022