I-Molnupiravir: Ipilisi eTshintshwayo yoMlomo yoNyango lwe-COVID-19

I-Molnupiravir, i-nucleoside analog ye-cytidine, ichiza elibonise ukufumaneka komlomo okugqwesileyo kunye neziphumo ezithembisayo kwiSigaba soku-1 kunye neSigaba sesi-2 solingo, sinokungqina ukuba yimbumbulu yomlingo esebenza njenge-arhente echasene nentsholongwane ye-virus ngokuchasene ne-SARS-CoV2 ebantwini. Izibonelelo eziphambili ze-molnupiravir vis a vis asele ekhona amayeza achasene nentsholongwane egazini kukuba anokuthathwa ngomlomo kwaye abonise ukuyiphelisa intsholongwane ye-SARS-CoV2 kwiiyure ezingama-24 kwizifundo zangaphambili kwi-ferrets..

Ubhubhani we-COVID-19 ubonakala unenkohliso kwaye awuqikeleleki kwihlabathi liphela. Ngelixa amazwe anje nge-United Kingdom evula kancinci kwaye ephumla ukuvalwa ngenxa yezehlo ezincitshisiweyo, i-France elandelayo ijonge i-wave lesithathu kwaye amazwe anje nge-Indiya ngoku ajongene nelona nqanaba libi lobhubhane ngaphandle kwawo onke amalungiselelo kunye nokwakhiwa kwamandla ngaphambili. Unyaka omnye. Nangona ungenelelo oluninzi lwezonyango luye lwazanywa ngokuchasene ne-COVID-19 olufana nokusetyenziswa kwe-dexamethasone kunye nokusetyenziswa kwamachiza alwa nentsholongwane egazini anjenge-favipravir kunye ne-remdesivir ukulwa esi sifo, ukuzingela kusaqhubeka kunyango olusebenzayo oluneekhompawundi ezingama-239 ezilwa nentsholongwane eziphantsi kophuhliso. kujoliswe kwizigaba ezahlukeneyo zomjikelo wobomi bentsholongwane¹. Ukongeza, ezinye iindlela ziyavavanywa ukuthintela ukungena kwentsholongwane kwiiseli ngokuphazamisana nokubophelela kwayo kwiseli yomkhosi. Oku kwenziwa nokuba kuphuhliswe iiproteni ezibophelela kwiiproteni ze-viral spike ngaloo ndlela zithintele ukusebenzisana kwayo I-ACE 2 i-receptor kwiseli yomkhosi okanye ukuphuhlisa i-ACE 2 receptor decoys ebophelela kwiprotein ye-spike yentsholongwane kwaye inqanda ukungena kwayo kwinginginya.  

Amanye amachiza aliqela enzelwe ukujolisa kwiiproteni zentsholongwane eziye zenziwa nje ukuba intsholongwane ingene kwiseli yomkhosi, ithathe oomatshini beselula kwaye iqalise ukwenza iiproteni zayo ukuze izisebenzisele uphindaphindo lwe-genome kwaye ekugqibeleni yenze amasuntswana entsholongwane amaninzi. Kwiiprotheyini ezininzi, eyona nto iphambili ekujoliswe kuyo yiprotheyini ixhomekeke kwi-RNA Iipolymera zeRNAe (RdRp) ekhuphela i-RNA. Izazinzulu zisebenzise ii-nucleoside ezininzi kunye ne-nucleotide analogs ukuqhatha i-RdRp ukuba izibandakanye kwi-RNA yentsholongwane ethi ekugqibeleni ijame i-RdRp kwaye iyeke ukuphindaphinda kwentsholongwane. Iianalogu ezininzi ezinjalo zisetyenzisiwe ezifana ne-favipiravir kunye ne-triazavirin, zombini eziyilelwe ukulwa iintsholongwane zomkhuhlane; i-ribavirin, esetyenziselwa ukuphefumla intsholongwane ye-syncytial kunye ne-hepatitis C; galidesivir, yokuthintela ukuphindaphinda kwe-Ebola, iZika, kunye neentsholongwane ze-yellow fever; kunye ne-remdesivir, ekuqaleni yayisetyenziswa ngokuchasene nentsholongwane ye-Ebola. 

Nangona ugonyo lunika ithemba elithile ngendlela yokunciphisa ubuqatha besifo ekufumaneni usulelo, oko akukuthinteli ukusasazeka kosulelo. Abantu basenokufumana usulelo nasemva kogonyo olusebenzayo esona sizathu esaneleyo sokukhawulezisa ukukhangela ii-anti-viral agents.¹, zombini i-spectrum ebanzi kunye neyodwa (ngendlela nje esinayo i-arsenal ye-antibiotics ngokumelene nebhaktheriya). Ukukhankanywa mva nje lichiza elibizwa ngokuba yi-Molnupiravir, i-nucleoside analog ye-cytidine, enokuthi ithathwe ngomlomo kwaye ibonakaliswe ukulwa usulelo lwe-coronavirus. UDenison kunye noogxa bakhe baxele ukuba i-molnupiravir inciphise ukuphindaphindwa kwee-coronavirus ezininzi, kubandakanya i-SARS-CoV-2, kwiimpuku.². Kubonakaliswe ukunciphisa ukuphindaphinda kwentsholongwane ka-100,000-kwiimpuku ezenziwe ukuba zibe nezicubu zemiphunga yomntu.³. Kwimeko yeeferrets, i-molnupiravir ayinciphisi nje kuphela iimpawu, kodwa ikhokelele ekosulelekeni yintsholongwane iqanda kwiiyure ezingama-24.⁴. Ababhali bolu phononongo babanga ukuba luphawu lokuqala lwechiza elifumaneka ngomlomo elivimba ngokukhawuleza usulelo lwe-SARS-CoV-2. Okubaluleke ngakumbi yayikukuba unyango lwe-molnupiravir luthintele usulelo lwentsholongwane kubafowunelwa ngokuthe ngqo abanganyangwanga ngaphandle kokuba kufutshane okuthe ngqo komthombo kunye nezilwanyana eziqhagamshelwayo. Le block epheleleyo inokunceda ekuthinteleni ukusasazeka ngempumelelo kwe SARS-CoV-2 intsholongwane. Kolunye uphononongo lwangaphambili kwi-hamsters, i-molnupiravir, idityaniswe ne-favipiravir ibonise amandla adityanisiweyo ekunciphiseni umthamo wentsholongwane egazini kunonyango nge-molnupiravir kunye ne-favipiravir yodwa.⁵.  

Uphononongo olungacwangciswanga, olungaboniyo oluphindwe kabini, olulawulwa yi-placebo, lokuQala kuMntu oluyilelwe ukuvavanya ukhuseleko, ukunyamezela, kunye ne-pharmacokinetics ye-molnupiravir elandela ukulawulwa komlomo kumavolontiya asempilweni kwizifundo ze-130 zizonke zibonisa ukuba i-molnupiravir yanyanyezelwa kakuhle kungekho nto ibalulekileyo. iziganeko ezimbi^6,7. Ngokusekwe kwezi ziphumo, uphononongo lweSigaba se-2 lwenziwa kwizigulana ezingama-202 ezingalaliswanga esibhedlele kwaye lwabonisa ukwehla okukhawulezileyo kwintsholongwane eyosulelayo phakathi kwabantu abaqale kwangoko. Covid-19 unyango nge-molnupiravir. Ezi ziphumo ziyathembisa kwaye ukuba zixhaswa ngezifundo ezongezelelweyo zesigaba se-2/3⁸ eziqhubekayo kunye nezifundo zesigaba sesi-3 eziye zaqhubekeka zinokuba neziphumo ezibalulekileyo kunyango kunye nokuthintela usulelo lwentsholongwane ye-SARS-CoV-2, eqhubeka ukusasazeka kwaye nokuvela kuninzi lwamazwe kwihlabathi liphela. Ukuba i-molnupiravir ibonisa iziphumo ezithembisayo kulingo olukhankanywe ngasentla, ingaqinisekisa isikali esikhulu kunye neendlela ezisebenzayo zemveliso ukuyivelisa ngobuninzi. Uphononongo lwakutsha nje olwenziwe ngu-Jamison kunye noogxa bakhe bachaze inkqubo ye-chromatography yasimahla ye-enzymatic enamanyathelo amabini okwenza i-molnupiravir esuka kwi-cytidine, inyathelo lokuqala libandakanya i-enzymatic acylation elandelwa kukudluliselwa kwemveliso yeyeza lokugqibela.⁹. Oku kuya kuba luncedo ngakumbi ngelixa kunyuswa imveliso yechiza ukuze kusetyenziswe urhwebo ukuphuhlisa inkqubo enexabiso eliphantsi ukwenza ukuba kufumaneke ichiza ngexabiso elifikelelekayo kumazwe achaphazelekayo ingakumbi amazwe asakhasayo nasaphuhlayo. 

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Ucaphulo  

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4. I-Cox, RM, Wolf, JD & Plemper, RK I-analogue ye-ribonucleoside elawulwa ngonyango i-MK-4482/EIDD-2801 iibhloko zokudluliselwa kwe-SARS-CoV-2 kwii-ferrets. Nat IMicrobiol 6, 11-18 (2021). https://doi.org/10.1038/s41564-020-00835-2  

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7. I-ClinicalTrial.gov 2021. I-Randomized, i-Double-Blind, i-Placebo-Controlled, i-First-in-Human Study eyenzelwe ukuHlola uKhuseleko, ukunyamezela, kunye ne-Pharmacokinetics ye-EIDD-2801 elandela uLawulo loMlomo kumaVolontiya aphilileyo. Umxhasi: Ridgeback Biotherapeutics, LP. Isazisi seClinicalTrials.gov: NCT04392219. Iyafumaneka kwi-intanethi https://clinicaltrials.gov/ct2/show/NCT04392219?term=NCT04392219&draw=2&rank=1 Ifikeleleke nge-20 ka-Epreli 2021.  

8. I-ClinicalTrial.gov 2021. ISigaba sesi-2/3, eRandomized, i-Placebo-Lawulwe, iSifundo seKlinikhi esingaboniyo kabini ukuVavanya ukuSebenza, uKhuseleko, kunye ne-Pharmacokinetics ye-MK-4482 kuBantu abadala abangaGwanga esibhedlele abane-COVID-19. Umxhasi: Merck Sharp & Dohme Corp. Isazisi seClinicalTrials.gov: NCT04575597. Iyafumaneka kwi-intanethi https://clinicaltrials.gov/ct2/show/NCT04575597?term=Molnupiravir&cond=Covid19&draw=2&rank=2 . Kufumaneka kwi-05 Meyi 2021. 

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