Njira Yatsopano Yothandizira 'Kukonzanso' Mankhwala Omwe Alipo a COVID-19

Kuphatikiza kwa biological and computational njira yophunzirira ma protein-protein interactions (PPIs) pakati pa ma virus ndi ma protein omwe amakhala nawo kuti azindikire ndikugwiritsanso ntchito mankhwala ochizira COVID-19 komanso matenda enanso..

Njira zanthawi zonse zothana ndi matenda obwera chifukwa cha ma virus zimaphatikizapo kupanga mankhwala oletsa ma virus komanso kupanga katemera. Muvuto lomwe silinachitikepo, dziko likukumana ndi chifukwa Covid 19 chifukwa cha SARS-CoV-2 virus, zotsatira za njira zonse zomwe zili pamwambazi zikuwoneka zakutali kwambiri kuti zipereke zotsatira zabwino zilizonse.

Gulu la ofufuza apadziko lonse lapansi posachedwapa (1) atengera njira yatsopano (kutengera momwe ma virus amalumikizirana ndi omwe amalandila) kuti "akonzenso" mankhwala omwe alipo ozindikiritsa mankhwala atsopano omwe akupangidwa, omwe angathandize kuthana ndi matenda a COVID-19 moyenera. Kuti amvetsetse momwe SARS-CoV-2 imagwirira ntchito ndi anthu, ofufuzawo adagwiritsa ntchito njira zophatikizira zachilengedwe komanso zama computa kuti apange "mapu" a mapuloteni amunthu omwe ma virus amalumikizana ndikugwiritsa ntchito kuyambitsa matenda mwa anthu. Ofufuzawo adatha kuzindikira mapuloteni aumunthu opitilira 300 omwe amalumikizana ndi mapuloteni a 26 omwe amagwiritsidwa ntchito mu kafukufukuyu (2). Chotsatira chinali kudziwa kuti ndi mankhwala ati omwe alipo komanso omwe akupangidwa omwe angakhale "kuwomboledwa” kuchiza matenda a COVID-19 poyang'ana mapuloteni a anthuwo.

Kafukufukuyu adatsogolera kuzindikirika kwa magulu awiri amankhwala omwe amatha kuchiza ndikuchepetsa matenda a COVID-19: zoletsa zotanthawuza mapuloteni kuphatikiza zotatifin ndi ternatin-4/plitidepsin, ndi mankhwala omwe amayang'anira kusintha kwa mapuloteni a Sigma1 ndi Sigma 2 receptors mkati mwa cell kuphatikiza progesterone, PB28, PD-144418, hydroxychloroquine, antipsychotic mankhwala haloperidol ndi cloperazine, siramesine, antidepressant ndi anti-anxiety mankhwala, ndi antihistamines clemastine ndi cloperastine.

Mwa zoletsa kumasulira kwa mapuloteni, mphamvu yamphamvu kwambiri ya antiviral mu vitro motsutsana ndi COVID-19 idawonedwa ndi zotatifin, yomwe pano ili m'mayesero azachipatala a khansa, ndi ternatin-4/plitidepsin, yomwe yavomerezedwa ndi FDA kuti ichite ma myeloma angapo.

Mwa mankhwala omwe amawongolera Sigma1 ndi Sigma2 zolandilira, antipsychotic haloperidol, yomwe imagwiritsidwa ntchito pochiza schizophrenia, imawonetsa antivayirasi yolimbana ndi SARS-CoV-2. Ma antihistamines awiri amphamvu, clemastine ndi cloperastine, adawonetsanso ntchito yoletsa ma virus, monga PB28. Mphamvu ya antivayirasi yowonetsedwa ndi PB28 inali yayikulu nthawi pafupifupi 20 kuposa hydroxychloroquine. Komano, Hydroxychloroquine, inasonyeza kuti, kuwonjezera pa kulunjika kwa Sigma1 ndi -2 receptors, imamangirizanso ku mapuloteni omwe amadziwika kuti hERG, omwe amadziwika kuti amayendetsa ntchito zamagetsi pamtima. Zotsatirazi zitha kuthandiza kufotokozera zoopsa zomwe zingachitike pogwiritsa ntchito hydroxychloroquine ndi zotumphukira zake ngati chithandizo cha COVID-19.

Ngakhale maphunziro a mu vitro omwe tawatchulawa atulutsa zotsatira zabwino, 'umboni wa pudding' udzadalira momwe mamolekyu amankhwala omwe angakhalepo akuyendera pamayesero azachipatala ndikupangitsa chithandizo chovomerezeka cha COVID-19 posachedwa. Kupadera kwa kafukufukuyu ndikuti kumakulitsa chidziwitso chathu pakumvetsetsa kwathu momwe kachilomboka kamalumikizirana ndi wolandirayo zomwe zimapangitsa kuzindikira mapuloteni amunthu omwe amalumikizana ndi ma virus komanso kuvumbulutsa mankhwala omwe mwina sakanatha kuwonekeratu kuti aphunzire mu ma virus.

Zomwe zavumbulutsidwa kuchokera mu kafukufukuyu sizinangothandiza asayansi kuzindikira omwe akuyembekezeredwa kumwa mankhwala mwachangu kuti akayezetse mayeso azachipatala, koma zitha kugwiritsidwa ntchito kumvetsetsa ndi kuyembekezera zotsatira zamankhwala omwe akuchitika kale kuchipatala komanso zitha kuonjezedwa kuti apeze mankhwala motsutsana ndi ena. ma virus ndi omwe si ma virus.

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Zothandizira:

1. The Institut Pasteur, 2020. Kuwulula momwe SARS-COV-2 imabera ma cell a Anthu; Amalozera ku mankhwala omwe angathe kulimbana ndi COVID-19 ndi mankhwala omwe amathandizira kukula kwake. PRESS RELEASE Yolembedwa pa 30 April 2020. Ipezeka pa intaneti pa 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 Adafikira pa 06 Meyi 2020.

2. Gordon, DE et al. 2020. Mapu olumikizana ndi mapuloteni a SARS-CoV-2 amawulula zomwe akufuna kugulitsanso mankhwala. Chilengedwe (2020). DOI: https://doi.org/10.1038/s41586-020-2286-9

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