Uphononongo lwakutsha nje luphuhlise ichiza elitsha elinokubakho elibanzi lokunyanga usulelo oluvela kwiHerpes Simplex Virus-1 kwaye mhlawumbi nezinye iintsholongwane kuzo zombini izigulana ezitsha kwaye ziye zaxhathisa kumachiza akhoyo.
Indlela yonyango yesiNtu kumayeza ibisoloko ilandela i-paradigm 'ye-bug-one-drug' apho ichiza (okanye ichiza) lijolise kuphela kwinto enye ebangela isifo emzimbeni. Abaphandi bafuna ukwamkela enye indlela yendlela enye iziyobisi enokujolisa kwiibugs ezininzi- uluhlu olubanzi amayeza anokuthi ajolise kwizinto ezininzi ezenza izifo. Amayeza amaninzi okubulala iintsholongwane akhoyo namhlanje asebenza ngokuchasene noluhlu olubanzi lweebhaktheriya ezibangela izifo kunye nomngundo. Olu hlobo lokubulala iintsholongwane olubanzi lunamandla kwaye lubhetyebhetye ngamachiza angenakusetyenziswa kuphela ngokuchasene neendidi ngeendidi zebhaktiriya kodwa anokusetyenziswa ukunyanga ezo ntsholongwane zibangela ibhaktiriya engekachongwa. Esona sithinteli-ntsholongwane sixhaphakileyo si-Ampicillin esinokuhlasela iintlobo ngeentlobo zebhaktiriya.
Ngokufana ne-antibiotics, i-spectrum ebanzi amachiza antiviral iya kuba neqhinga lokujolisa kwiintlobo ezahlukeneyo zeentsholongwane. Ekusebenzisani le ndlela yee-antivirals, abaphandi kufuneka bachonge iimpawu ezahlukeneyo zenginginya leyo iintsholongwane 'zixhomekeke' kumjikelo wabo wobomi. Iintsholongwane zahluke kakhulu kwiibhaktheriya kwaye njengoko iintsholongwane ziqweqwedisa oomatshini bethu beeselula kunzima kakhulu ukuphazamisa ukukhula kwentsholongwane ngaphandle kokubangela ukuphazamiseka ekusebenzeni kweeseli zomntu. Kodwa ekubeni iintlobo ngeentlobo zeentsholongwane zithatha ithuba lomsebenzi omnye womamkeli, ichiza elibanzi lokuthomalalisa iintsholongwane linokuthi 'lithintele' intsholongwane kulo naluphi na ufikelelo kumsebenzi wokusingatha ngaloo ndlela ibulala intsholongwane, nokuba yeyiphi na intsholongwane. Uninzi lwee-antivirals ziye zasilela ekuhambeni kweminyaka kuba iintsholongwane zahlukile kwiibhaktheriya njengoko ziguquka ngokukhawuleza. Ichiza le-antiviral eliphuhliswa emva kweminyaka yokusebenza ngokubanzi linobomi obuncinci beshelufu kwaye amayeza alwa neentsholongwane anomlinganiselo omxinwa wokuhlasela ukuqala ngawo kuba ahlasela kuphela uhlobo oluthile. intsholongwane. Ukusukela ngo-2018, amayeza akakafumaneki kwiintsholongwane ezininzi, umzekelo, i-Ebola. Isithinteli-ntsholongwane esinamandla, esikhuselekileyo nesisebenzayo esinobubanzi obubanzi sinokujolisa kwindlela yokusingatha iintsholongwane kwaye sibulale iintlobo ngeentlobo zeentsholongwane.
Ngokutsho kwe-WHO, kuqikelelwa ukuba i-3.7 yezigidigidi zabantu emhlabeni jikelele abangaphantsi kweminyaka engama-50 ubudala bosulelwe yi-herpes simplex virus 1 (HSV-1). I-HSV-1 lusulelo lwentsholongwane oluxhaphakileyo oluxhaphakileyo oluqhubeka ubomi bonke nokuba lufunyenwe ngexesha lobuntwana okanye ukufikisa. Le ntsholongwane yosulela ikakhulu emlonyeni kunye namehlo kodwa ngamanye amaxesha ikwachaphazela namalungu obuni. Njengoninzi losulelo lwentsholongwane lunwenwa lula kwaye kulucelomngeni olunzima ukuluthintela. Amachiza ambalwa onyango akhoyo kolu sulelo aphumelele kakhulu, nangona kunjalo intsholongwane iye yavela kwiintlobo ezixhathisa amachiza ingakumbi emva kokusetyenziswa kwexesha elide kuba uninzi lwala machiza lulandela indlela eqhelekileyo yonyango.
Unyango olutsha losulelo lwe-HSV-1
Ukosuleleka kwiliso kunokupheliswa okwethutyana kusetyenziswa amachiza athomalalisayo afumanekayo kodwa ukudumba kwicornea – umaleko ongaphandle webhola yamehlo – kubonakala kuqhubeka ngokungapheliyo okukhokelela kwezinye iimeko ezifana neglaucoma kunye nokungaboni ngokusetyenziswa ngokugqithisileyo kwamayeza e-steroids. Amachiza akhoyo emarikeni, abizwa ngokuba zii-nucleoside analogues, athintela intsholongwane ekuveliseni iprotein ebaluleke kakhulu ekuphindaphindeni nasekukhuleni kwentsholongwane. Nangona kunjalo, ukunganyangeki kumachiza ngumba obalulekileyo kwaye izigulane eziphuhla ukuxhathisa ezi analogu zishiywe zinokhetho olulinganiselweyo lokunyanga usulelo lwe-HSV-1. Kuphononongo lwakutsha nje olupapashwe kwi Inzululwazi yokuguqulela isayensi, Abaphandi bachonge imolekyuli encinci yechiza ecoca usulelo lwe-HSV-1 kwiiseli zecornea ngokusebenza ngokwahlukileyo kakhulu kunamachiza akhoyo okwenza ukuba libe lichiza elithembisayo elichasene ne-HSV-1.
Imolekyuli encinci yeziyobisi - ebizwa BX795 - icoca usulelo kwiiseli ze-cornea yabantu (ezikhuliswe elabhoratri) kunye neekhoneya zeempuku ezosulelekileyo. I-BX795 ilandela indlela entsha esebenza ngayo kwiiseli zomkhosi ukucoca usulelo lwentsholongwane. Le molekyuli yi-inhibitor eyaziwayo ye-enzyme TBK1 ebandakanyeka kwi-immunity kwi-host, okanye ngakumbi ngakumbi kwi-innate immunity kunye neuroinflammation. Kuye kwasekwa phambi kokuba ukunqongophala kwe-TBK1 inxalenye ethile kubangele ukuphazamiseka kwe-neuroinflammatory okanye neurodegenerative. Kuphononongo lwangoku, xa le enzyme yayicinezelwe, usulelo lwentsholongwane lwabonwa lukhula. Nangona kunjalo, kwelinye icala, ukugxilwa okuphezulu kwe-BX795 kwabonwa ukucoca usulelo lwe-HSV-1 kwiiseli. I-BX795 isebenza ngokujolisa kwindlela ye-AKT phosphorylation kwiiseli ezosulelekileyo ngaloo ndlela ivalela iprotein yentsholongwane. I-HSV-1 iyaziwa ngokuvula indlela ye-AKT ukuze isebenzise iprotheni synthesis kunye nokuxhasa ukungena kwentsholongwane kunye nokuphindaphinda. Lilonke, ukugxila okusezantsi kwale molekyuli bekufuneka ukucoca usulelo xa kuthelekiswa ne-nucleoside analogues. Akukho tyhefu okanye naziphi na ezinye iziphumo ezazibonakala kwiiseli ezingosulelwanga. Ababhali baxela ukuba inguqulelo yedosi yedosi yasetyenziswa kwizifundo kwaye baphakathi kokuqulunqa idosi yomlomo efanayo.
Ingaba i-BX795 ingasetyenziselwa ukujolisa olunye usulelo lwentsholongwane?
Umbuzo obalulekileyo ekufuneka ucamngce ngawo ngowokuba ingaba indlela yonyango efanayo ingasetyenziswa na kolunye usulelo olubalulekileyo lwentsholongwane egazini njenge-HSV-2 (herpes simplex virus 2) okanye i-HIV (human immunodeficiency virus). Kuba iintsholongwane ezininzi zilandela indlela eqhelekileyo yokuphindaphinda ngaphakathi kwiseli yomkhosi, kwaye iBX795 ijolise kuloo ndlela, oku kunokuba luhlobo olutsha lwe-antiviral ebanzi enokuthi isetyenziswe ukunyanga nolunye usulelo lwentsholongwane. Umzekelo, usulelo lwe-Human Papillomavirus (HPV) lunokujoliswa ngendlela efanayo ngokuthintela i-AKT phosphorylation kwiiseli ze-host eyimfuneko kwi-HPV ukuba isasazeke.
Ukuguqulelwa kwezifundo zaselabhoratri zamayeza abanzi kuvavanyo lwezilwanyana kubalulekile. Umzimba wethu uzaliswe ziintsholongwane eziluncedo nazo (izigidi ngezigidi mhlawumbi) ezinokuba yimfuneko kwimpilo yethu, kubandakanywa iintsholongwane ezosulela iintsholongwane kunye ne-antiviral ebanzi inokuthintela ezi ntsholongwane zilungileyo nazo. Nangona kunjalo, ezinye ii-antivirals ezinobubanzi obubanzi ziyafuneka njengoko ukunganyangeki ngamachiza kuba yingxaki yehlabathi kwaye kwiintsholongwane ezininzi amachiza akafumaneki. Oku kufunyenweyo kukhangeleka kuthembisa izigulane ezitsha ngokunjalo nakwizigulane ezithe zanganyangeki kumachiza akhoyo. Uphando olongezelelweyo lunokuseka amandla achanekileyo ale molekyuli entsha yechiza.
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{Unokufunda iphepha lokuqala lophando ngokunqakraza ikhonkco le-DOI elinikwe ngezantsi kuluhlu lwemithombo ecatshulweyo (s)}
Umthombo (s)
Jaishankar et al. 2018. Umphumo ojoliswe kuyo we-BX795 uvimba uhlobo lwentsholongwane ye-herpes simplex 1 usulelo lweso. Inzululwazi yokuguqulela isayensi. 10(428). https://doi.org/10.1126/scitranslmed.aan5861
