Indibaniselwano yebhayoloji kunye nendlela yokubala yokufunda ukusebenzisana kweeprotheyini (iiPPIs) phakathi kwentsholongwane kunye neeproteni ezibamba iiproteni ukuze kuchongwe kwaye kusetyenziswe amachiza kwakhona kunyango olusebenzayo lwe-COVID-19 kwaye kunokwenzeka nolunye usulelo ngokunjalo..
Amacebo aqhelekileyo okujongana nosulelo lwentsholongwane egazini lubandakanya ukuyila amachiza okulwa nentsholongwane kunye nophuhliso lwezitofu zokugonya. Kwingxaki engazange ibonwe ngoku, ihlabathi lijongene nalo ngenxa Covid-19 ebangelwa yi-SARS-CoV-2 intsholongwane, iziphumo eziphuma kuzo zombini ezi ndlela zingasentla zibonakala zikude kakhulu ukuzisa naziphi na iziphumo ezinethemba.
Iqela labaphandi bamazwe ngamazwe kutsha nje (1) baye bamkela indlela entsha (esekwe kwindlela iintsholongwane ezinxibelelana ngayo nabamkeli-zindwendwe) “zokwenza injongo kwakhona” yamachiza asele ekhona okuchonga amachiza amatsha asaphuhliswayo, anokunceda ukulwa usulelo lwe-COVID-19 ngokufanelekileyo. Ukuze uqonde ukuba i-SARS-CoV-2 inxibelelana njani nabantu, abaphandi basebenzise indibaniselwano yebhayoloji kunye neendlela zokubala ukwenza "imephu" yeeproteni zabantu ezithi iiproteni zentsholongwane zinxibelelane nazo kwaye zisebenzise ukubangela usulelo ebantwini. Abaphandi baye bakwazi ukuchonga ngaphezu kweeprotheyini ze-300 zabantu ezisebenzisana neeprotheni zentsholongwane ze-26 ezisetyenziswe kwisifundo (2). Inyathelo elilandelayo ibikukuchonga ukuba ngawaphi amachiza akhoyo kunye nalawo asaphuhliswayo anokuba “ibuyiselwe kwakhona” ukunyanga usulelo lwe-COVID-19 ngokujolisa kwezo proteni zabantu.
Uphando lukhokelele ekuchongweni kweendidi ezimbini zamachiza ezinokunyanga ngempumelelo kunye nokunciphisa isifo se-COVID-19: ii-protein inhibitors zokuguqulela ezibandakanya i-zotatifin kunye ne-ternatin-4/plitidepsin, kunye namachiza anoxanduva lokumodareyitha iproteni ye-Sigma1 kunye ne-Sigma 2 receptors ngaphakathi iseli kuquka iprogesterone, PB28, PD-144418, hydroxychloroquine, iziyobisi antipsychotic haloperidol kunye cloperazine, siramesine, ichiza lokudakumba kunye anti-anxiety, kunye antihistamines clemastine kunye cloperastine.
Kwiprotheyini yokuguqulela inhibitors, eyona mpembelelo inamandla ye-antiviral kwi-vitro ngokuchasene ne-COVID-19 yabonwa nge-zotatifin, ekungokunje kulingo lwezonyango lomhlaza, kunye ne-ternatin-4/plitidepsin, eyamkelwe yi-FDA kunyango lwe-myeloma eninzi.
Phakathi kwamachiza amodareyitha i-Sigma1 kunye ne-Sigma2 receptors, i-antipsychotic haloperidol, esetyenziselwa ukunyanga i-schizophrenia, ibonise umsebenzi we-antiviral ngokuchasene ne-SARS-CoV-2. Ii-antihistamines ezimbini ezinamandla, i-clemastine kunye ne-cloperastine, nazo zibonise umsebenzi we-antiviral, njengoko yenza i-PB28. Isiphumo sokulwa nentsholongwane egazini esiboniswe yi-PB28 sasimalunga namaxesha angama-20 amakhulu kune-hydroxychloroquine. I-Hydroxychloroquine, kwelinye icala, ibonise ukuba, ngaphezu kokujolisa kwi-Sigma1 kunye ne-2 receptors, iphinda ibophe kwiprotheni eyaziwa ngokuba yi-hERG, eyaziwa ngokulawula umsebenzi wombane entliziyweni. Ezi ziphumo zinokunceda ukuchaza imingcipheko enokubakho enxulumene nokusebenzisa i-hydroxychloroquine kunye nezinto eziphuma kuyo njengonyango olunokubakho lwe-COVID-19.
Nangona uphononongo lwe-in vitro lukhankanywe ngasentla luvelise iziphumo ezithembisayo, 'ubungqina bepudding' buya kuxhomekeka kwindlela ezi molekyuli zamachiza ezinokubakho ziqhuba njani kulingo lwezonyango kwaye zikhokelele kunyango oluvunyiweyo lwe-COVID-19 kungekudala. Ukwahluka kolu phando kukuba kwandisa ulwazi lwethu ekuqondeni kwethu okusisiseko malunga nendlela intsholongwane enxibelelana ngayo nomntu okhokelela ekuchongeni iiproteni zabantu ezinxibelelana neeproteni zentsholongwane kunye nokutyhila iikhompawundi ezinokuthi ngenye indlela zingabonakali ukuba zifundelwa kwimeko yentsholongwane.
Olu lwazi lutyhilwe kolu phononongo aluzange luncede izazinzulu kuphela ukuba zichonge abaviwa amayeza athembisayo ngokukhawuleza ukuba balandele ulingo lwezonyango, kodwa lunokusetyenziselwa ukuqonda kunye nokulindela isiphumo sonyango esele lusenzeka ekliniki kwaye lunokwandiswa ukuze kufunyanwe ichiza ngokuchasene nezinye. izifo zentsholongwane kunye ne-non-virus.
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Iingxelo:
1. I-Institut Pasteur, 2020. Ityhila indlela iSARS-COV-2 eziqweqwedisa ngayo iiseli zaBantu; Isalatha kumachiza anamandla okulwa i-COVID-19 kunye nechiza elinceda ukukhula okosulelayo. I-PRESS RELEASE ithunyelwe nge-30 ku-Epreli 2020. Iyafumaneka kwi-intanethi https://www.pasteur.fr/en/research-journal/press-documents/revealing-how-sars-cov-2-hijacks-human-cells-points-drugs-potential-fight-covid-19-and-drug-aids-its Ifikeleleke nge-06 Meyi 2020.
2. UGordon, uDE et al. 2020. Imephu ye-SARS-CoV-2 yeprotheyini yokunxibelelana ityhila ekujoliswe kuko ekuthengiseni kwakhona ichiza. Indalo (2020). DOI: https://doi.org/10.1038/s41586-020-2286-9
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