E mafaiPapain-pei o le protease inhibitor e faasaga ile COVID-19? I se suʻesuʻega talu ai nei na lafoina i le bioRxiv* preprint server, na iloa ai e le au suʻesuʻe se faʻamaʻi papaini e pei o le protease inhibitor mo le togafitia o faʻamaʻi pipisi o le coronavirus 2 (SARS-CoV-2) ogaoga.
SARS-CoV-2 main protease (Mpro) inhibitors o le auala muamua lea i le atinaʻeina o togafitiga o le coronavirus faʻamaʻi 2019 (COVID-19) lea na mafua ai le faʻatagaina o le nirmatrelvir (Paxlovid) mo faʻalavelave faʻafuaseʻi.O le Mpro ua avea ma faʻamoemoega faʻamoemoe mo vailaʻau fou ona o lona le tutusa ma tagata protease ma lona taua i taimi o faʻamaʻi.Ae, o le tele o suʻesuʻega e naʻo le taulaʻi atu i le atinaʻeina o le au taʻitoʻatasi Mpro.
O lepapainimotusia le peptide bonds mechanism lea e aofia ai le fa'aogaina o se catalytic dyad ma se cysteine deprotonated.O se Asn-175 lata ane e fesoasoani i le faʻaogaina o le mama imidazole o Lana-159 e faʻatagaina ai ona faʻaumatia le catalytic Cys-25.Ona faia lea e le cysteine lea se osofa'iga nucleophilic i le carbonyl carbon o se peptide backbone.O lenei mea e fausia ai se covalent acyl-enzyme intermediate ma faʻasaʻoloto le amino pito o le peptide.O le enzyme e fa'apalapala e se mole vai ma fa'asa'oloto le vaega fa'amau o le peptide.I le immunology, ua iloa le papain e vavae le vaega Fc (crystallisable) o immunoglobulins (antibodies) mai le vaega Fab (antigen-binding).
E uiga i leSa'oga
mo su'esu'ega i le taimi nei, na fa'ailoa mai e le au su'esu'e se protease pei o papain (PLpro) e mafai ona fa'aoga fa'atasi ma se fa'atosina Mpro i totonu o se fa'amalama fa'atosina protease mo togafitiga SARS-CoV-2.
Na fa'apipi'iina le tele o mea fa'avae naphthalene (Ata Fa'aopoopo 2) ma fa'ata'ita'iina mo le fa'asaina o le gaioiga o le SARS-CoV-2 PLpro (Fa'aopoopo Ata 3).O se tasi o nei tuufaatasiga (1/GRL0617) na faailoa muamua o se fa'ama'i fa'apitoa SARS-CoV PLpro, ma fa'aalia ai le malosi lelei ma le maualalo o le cytotoxicity i le SARS-CoV-a'afia Vero E6 sela33.Matou te tuʻuina atu i lenei tusitusiga taunuʻuga o biochemical, cell atoa, ma suʻesuʻega tioata maualuga maualuga o faʻalapotopotoga e fitu, ono o loʻo i ai le methyl-N- [(1R) -1-naphthalen-1-ylethyl] benzamide scaffold ma le tasi o se analog faʻafaigofie o a tatou lava mamanu.O mea uma nei e taofia ai le SARS-CoV-2 PLpro protease ma o loʻo taʻua i lalo: 1 o le 5-amino-2-methyl-N-[(1R)-1-naphthalen-1-ylethyl]benzamide (GRL0617), 2 o le. 5-carbamylurea-2-methyl-N-[(1R) -1-naphthalen-1-ylethyl]benzamide, 3 o le 5-acrylamide-2-methyl-N-[(1R) -1-naphthalen-1-ylethyl] benzamide, 4 o le 3-amino-N-(naphthalene-1-yl) -5-trifluoromethyl)benzamide, 5 o le 5-(butylcarbamoylamino) -2-methyl-N-[(1R) -1-naphthalen-1-ylethyl ]benzamide, 6 o le 5-(((4-nitrophenoxy)carbonyl)amino)-2-methyl-N-[(1R)-1-naphthalen-1-ylethyl]benzamide, ma le 7 o le 5-pentanoylamino-2-methyl -N-[(1R)-1-naphthalen-1-ylethyl]benzamide (Ata 2 ma Ata Faaopoopo 2A).
I'uga
O suʻesuʻega suʻesuʻega na faʻaalia ai o le suʻesuʻeina o laʻititi laʻititi na maua ai faʻailoga e fa na faʻaalia ai le PLpro inhibitory activity o le sili atu i le 80%, e taʻua o le eltrombopag (DDL-701), o le cysteinyl leukotriene antagonist e taʻua o zafirlukast (DDL-715), thrombopoietin receptor agonist-1 (TPO-1 agonist, DDL-713), ma le GRL-0617.E le gata i lea, o se vailaʻau antipsychotic e taʻua o le fluspirilene ma le leukotriene receptor antagonist e taʻua o le montelukast faʻateleina le gaioiga PLpro.
Fa'ai'uga
Ae ui i lea, o loʻo i ai naʻo ni lipoti i le taimi nei, ma e tatau ona tatou faʻatali mo le malo e faʻasalalau le faʻamatalaga Pe sili atu le faʻatagaina o lipoti.
Taimi meli: Aukuso-24-2022