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'Bradykinin Hypothesis' Inotsanangura Iyo Yakawedzera Kuzvimba Mhinduro muCOVID-19

A novel mechanism yekutsanangura zvakasiyana-siyana zvisina hukama zviratidzo zve Covid-19 yabuda pachena nekushandisa yechipiri inokurumidza Supercomputer munyika inozivikanwa seSummit supercomputer paOak Ridge National Lab muTennessee. Chidzidzo ichi chaisanganisira kuongorora 2.5 bhiriyoni musanganiswa wemajini kubva ku17000 genetic samples uye anopfuura 40,000 majini kuitira kuti tinzwisise zviri nani chiitiko chine njodzi icho. Covid-19 inoshanda pamuviri wemunhu. Zvakatora rinenge vhiki kuongorora izvi genetic musanganiswa uye vaongorori vakauya nedzidziso nyowani inonzi bradykinin hypothesis.1, izvo hazvingotsananguri zvimwe zvezvinoshamisa uye zvakasiyana-siyana zviratidzo zve Covid-19 asi zvakare inopa mazano ekurapa anogona, mazhinji acho akatotenderwa neFDA. 

Iyo SARS-CoV-2 hutachiona hunokonzera Covid-19 kazhinji inopinda mumuviri nekusunga kune ACE2 receptors (iripo mukuwanda mumasero emhino). Zvinozoenderera mberi nekutapurira dzimwe nhengo dzemuviri senge ura, itsvo nemoyo uko ACE2 receptors aripo.  

Ongororo yacho yakawana kuti SARS-CoV-2 yakakonzera kuwedzera kwemazinga eACE2 uku ichidzika mazinga eACE mumasero emapapu.2. Basa rakajairwa reACE2 mumuviri wemunhu nderokudzikisa BP uye rinoshanda rinopesana neimwe enzyme inozivikanwa seACE (iyo ine zvinopesana). Naizvozvo, muviri unofanirwa kuenzanisa mazinga eACE neACE2 kuchengetedza yakajairika BP. Kuwedzera kwemazinga eACE2 uye kudzikira kweACE kwakakonzera kuwedzera kwemazinga emorekuru anozivikanwa sebradykinin mumaseru (inonzi 'Bradykinin Storm'). Bradykinin yakaratidzwa kuti inokonzera marwadzo uye inoita kuti tsinga dzeropa dziwedzere uye dzive dzakasviba izvo zvinogona kutungamirira mukuzvimba uye kuzvimba kwenyama yakapoteredza. 

Bradykinin mis-regulation inodzorwa neyakakura sisitimu inonzi Renin Angiotensin System (RAS) iyo inodzora akawanda maficha eiyo circulatory system uye inosanganisira enzymes ACE2 uye ACE. Iyo SARS-CoV-2 hutachiona pahutachiona inonyengedza maseru emuviri kuti awedzere ACE receptors nekudaro achiwedzera ACE2 uye kutapukirwa kwemamwe masero. Bradykinin receptors zvakare inokurudzirwa zvakare, uye muviri unomirawo zvinobudirira kuputsa bradykinin nekuda kwekuderera kweACE sezvataurwa pamusoro. ACE inowanzodiwa pakusvibisa bradykinin. 

Pamusoro pebradykinin dutu, kuongororwa kwekombuta kwakawanawo kuti kugadzira hyaluronic acid yakawedzera uye ma enzymes anoisvibisa akadzikira zvakanyanya. Izvi zvinokonzeresa kukwira kwakanyanya kwehyaluronic acid iyo inotora mvura kuita hydrogel3. Kubuda kwemvura mumapapu kunokonzerwa nedutu rebradykinin pamwe neakawandisa hyaluronic acid mhedzisiro inodzivirira kukwira kweokisijeni yakakwana uye kuburitswa kwecarbon dioxide mumapapu eakakanganisika zvakanyanya. Covid-19 varwere. Izvi zvinotsanangura chikonzero nei maventilator akaratidzwa kuti haashande muvarwere vakadai sezvo zvisinei kuti ndeipi mwero weokisijeni yaunopa, mapapu haakwanise kuipedza nekuda kwekuvapo kwehydrogel mumapapu zvichitungamira mukudzipwa uye kufa muvarwere. 

Iyo bradykinin hypothesis inogona zvakare kutsanangura iyo yemoyo uye neurological mhedzisiro inoonekwa mukati Covid-19 varwere. Madutu eBradykinin anogona kutungamira kune arrhythmias uye kuderera kweropa, izvo zvinowanzoonekwa muvarwere veCovid-19. Kuwedzera bradykinin mazinga anogona zvakare kutungamirira mukuparara kweropa-brain barriers zvichikonzera kuzvimba uye kukuvara kwehuropi. 

Imwe kirasi yemakomponi inozivikanwa seACE inhibitors ine mhedzisiro yakafanana paRAS system seCOVID-19, ne. kuwedzera bradykinin mazinga. Zvinoita sokuti SARS-CoV-2 inoshanda nenzira yakafanana neACE inhibitors. Iwo maviri ekirasi zviratidzo zveCovid-19, chikosoro chakaoma uye kuneta zvinokonzereswa neACE inhibitors. Uye zvakare, ACE inhibitors zvakare inokonzeresa kurasikirwa nekunhuhwirira, zvakare kunoonekwa muCOVID-19 varwere. 

Kana iyo bardykinin hypothesis ichifanirwa kutendwa, saka kwatove neFDA yakatenderwa mishonga iripo inogona kuderedza bradykinin mazinga uye nekudaro inopa zororo kubva kuCOVID-19. Mishonga iyi inosanganisira danazol, stanozolol, uye ecallantide, iyo inogona kuderedza kugadzirwa kwebradykinin uye inogona kumisa dutu rebradykinin. Chidzidzo ichi zvakare chinonongedza kushandiswa kweVitamin D semushonga nekuti inobatanidzwa muRAS system sezvo ichideredza mazinga emukomboni, unozivikanwa seREN. Izvi zvinogona kumisa madutu anouraya ebradykinin. Vitamin D yakatove yakabatanidzwa muCOVID-19 sezvakatsanangurwa pakutangauko kusakwana Vitamin D kunokonzera zvakakomba COVID-19 zviratidzo. Mimwe mishonga inogona kushandiswa ndiyo inoderedza hyaluronic acid level, eg Hymecromone inogona kushandiswa kumisa mahydrogel kuti asaumbike mumapapu. 

Kunyangwe chidzidzo ichi chichitsanangura fungidziro inotsanangura zvingangoita zvese zveCCIDID-19 zviratidzo kusvika parizvino uye ichipa dzidziso yakabatana inogona kuongororwa uchishandisa mishonga iripo, humbowo chaihwo hwepudding huchabva mukuyedza mishonga iripo chete kana musanganiswa yakanyatso gadzirwa miedzo yekiriniki kuti iuye nerejimendi yekurapa iyo inotungamira kune inogoneka kurapwa kweCOVID-19. 

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References 

  1. Garvin MR, Alvarez C, Miller JI, Prates ET, Walker AM et al. Iyo mechanistic modhi uye yekurapa kupindira kweCCIDID-19 inosanganisira RAS-mediated bradykinin dutu. eLife 2020;9: e59177 DOI: https://doi.org/10.7554/ELIFE.59177  
  1. Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W et al. Pneumonia kubuda kwakabatana neiyo coronavirus nyowani yeanogona bat yakabva. Zvisikwa 2020. 579:270–273. DOI: https://doi.org/10.1038/S41586-020-2012-7 
  1. Necas J, Bartosikova L, Brauner P, Kolar J. Hyaluronic acid (hyaluronan): wongororoVeterinární Medicína (2008). 53:397–411. DOI: https://doi.org/10.17221/1930-VETMED 
  1. Soni R., 2020. Vitamin D Kusakwana (VDI) Kunotungamira kune Zvakakomba COVID-19 Zviratidzo. Scientific European. Inowanikwa online pa https://www.scientificeuropean.co.uk/covid-19/vitamin-d-insufficiency-vdi-leads-to-severe-covid-19-symptoms/ Inowanikwa pa4th September 2020. 

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Rajeev Soni
Rajeev Sonihttps://web.archive.org/web/20220523060124/https://www.rajeevsoni.org/publications/
Dr. Rajeev Soni (ORCID ID : 0000-0001-7126-5864) ane Ph.D. muBiotechnology kubva kuYunivhesiti yeCambridge, UK uye ane makore makumi maviri nemashanu echiitiko chekushanda pasi rose muzvikoro zvakasiyana-siyana uye marudzi akawanda akadai seThe Scripps Research Institute, Novartis, Novozymes, Ranbaxy, Biocon, Biomerieux uye semuongorori mukuru neUS Naval Research Lab. mukuwanikwa kwezvinodhaka, kuongororwa kwema molecular, protein expression, biologic kugadzira uye kusimudzira bhizinesi.

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