Matches in SemOpenAlex for { <https://semopenalex.org/work/W4366607162> ?p ?o ?g. }
- W4366607162 endingPage "105607" @default.
- W4366607162 startingPage "105607" @default.
- W4366607162 abstract "Zika virus (ZIKV) infection is associated with the birth defect microcephaly and Guillain–Barré syndrome in adults. There is no approved vaccine or specific antiviral agent against ZIKV. ZFD-10, a novel structural skeleton of 1H-pyridazino[4,5-b]indol-4(5H)-one, was firstly synthesized and discovered to be a potent anti-ZIKV inhibitor with very low cytotoxicity. ZFD-10's anti-ZIKV potency is independent of cell lines and ZFD-10 mainly targets the post-entry stages of ZIKV life cycle. Time-of-addition and time-of-withdrawal assays showed that 10 μM ZFD-10 displayed the ability to decrease mainly at the RNA level and weakly the viral progeny particle load. Furthermore, ZFD-10 could protect ZIKV NS5 from thermal unfolding and aggregation and increase the Tagg value of ZIKV NS5 protein from 44.6 to 49.3 °C, while ZFD-10 dose-dependently inhibits ZIKV NS5 RdRp activity using in vitro RNA polymerase assays. Molecular docking study suggests that ZFD-10 affects RdRp enzymatic function through interfering with the fingers and thumb subdomains. These results supported that ZFD-10's cell-based anti-ZIKV activity is related to its anti-RdRp activity of ZIKV NS5. The in vivo anti-ZIKV study shows that the middle-dose (4.77 mg/kg/d) of ZFD-10 protected mice from ZIKV infection and the viral loads of the blood, liver, kidney and brain in the middle-dose and high-dose (9.54 mg/kg/d) were significantly reduced compared to those of the ZIKV control. These results confirm that ZFD-10 has a certain antiviral effect against ZIKV infection in vivo." @default.
- W4366607162 created "2023-04-23" @default.
- W4366607162 creator A5002431613 @default.
- W4366607162 creator A5006094386 @default.
- W4366607162 creator A5007108734 @default.
- W4366607162 creator A5009277330 @default.
- W4366607162 creator A5038143691 @default.
- W4366607162 creator A5051959933 @default.
- W4366607162 creator A5056788729 @default.
- W4366607162 creator A5070942311 @default.
- W4366607162 creator A5076498328 @default.
- W4366607162 creator A5079598561 @default.
- W4366607162 creator A5081844561 @default.
- W4366607162 creator A5089048021 @default.
- W4366607162 creator A5090728786 @default.
- W4366607162 date "2023-06-01" @default.
- W4366607162 modified "2023-09-30" @default.
- W4366607162 title "Discovery of ZFD-10 of a pyridazino[4,5-b]indol-4(5H)-one derivative as an anti-ZIKV agent and a ZIKV NS5 RdRp inhibitor" @default.
- W4366607162 cites W1932632320 @default.
- W4366607162 cites W1973619678 @default.
- W4366607162 cites W2011252618 @default.
- W4366607162 cites W2019512434 @default.
- W4366607162 cites W2027598863 @default.
- W4366607162 cites W2042530028 @default.
- W4366607162 cites W2045861647 @default.
- W4366607162 cites W2073049582 @default.
- W4366607162 cites W2117119827 @default.
- W4366607162 cites W2163412375 @default.
- W4366607162 cites W2269179130 @default.
- W4366607162 cites W2281227512 @default.
- W4366607162 cites W2289704315 @default.
- W4366607162 cites W2335029448 @default.
- W4366607162 cites W2389906561 @default.
- W4366607162 cites W2463187558 @default.
- W4366607162 cites W2485464167 @default.
- W4366607162 cites W2523471482 @default.
- W4366607162 cites W2576816878 @default.
- W4366607162 cites W2590495675 @default.
- W4366607162 cites W2599913756 @default.
- W4366607162 cites W2608473018 @default.
- W4366607162 cites W2609300759 @default.
- W4366607162 cites W2615109422 @default.
- W4366607162 cites W2734954484 @default.
- W4366607162 cites W2789872472 @default.
- W4366607162 cites W2807409322 @default.
- W4366607162 cites W2809841748 @default.
- W4366607162 cites W2883302210 @default.
- W4366607162 cites W2886175106 @default.
- W4366607162 cites W2898261182 @default.
- W4366607162 cites W2932731310 @default.
- W4366607162 cites W2954449798 @default.
- W4366607162 cites W2975158828 @default.
- W4366607162 cites W2991620597 @default.
- W4366607162 cites W2994576593 @default.
- W4366607162 cites W3017165458 @default.
- W4366607162 cites W3039744401 @default.
- W4366607162 cites W3041182781 @default.
- W4366607162 cites W3041381429 @default.
- W4366607162 cites W3048560933 @default.
- W4366607162 cites W3048796709 @default.
- W4366607162 cites W3080645386 @default.
- W4366607162 cites W3082228993 @default.
- W4366607162 cites W3088015719 @default.
- W4366607162 cites W3113638129 @default.
- W4366607162 cites W3174052286 @default.
- W4366607162 cites W3180956394 @default.
- W4366607162 cites W3190601417 @default.
- W4366607162 cites W3191826740 @default.
- W4366607162 cites W3193620359 @default.
- W4366607162 cites W3198079965 @default.
- W4366607162 cites W3206931712 @default.
- W4366607162 cites W3212125237 @default.
- W4366607162 cites W3217505830 @default.
- W4366607162 cites W4207074393 @default.
- W4366607162 cites W4214944251 @default.
- W4366607162 cites W4225164043 @default.
- W4366607162 cites W4225666420 @default.
- W4366607162 cites W4226412880 @default.
- W4366607162 cites W4280494781 @default.
- W4366607162 cites W4281680793 @default.
- W4366607162 cites W4313530197 @default.
- W4366607162 cites W4319333871 @default.
- W4366607162 doi "https://doi.org/10.1016/j.antiviral.2023.105607" @default.
- W4366607162 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37088168" @default.
- W4366607162 hasPublicationYear "2023" @default.
- W4366607162 type Work @default.
- W4366607162 citedByCount "2" @default.
- W4366607162 countsByYear W43666071622023 @default.
- W4366607162 crossrefType "journal-article" @default.
- W4366607162 hasAuthorship W4366607162A5002431613 @default.
- W4366607162 hasAuthorship W4366607162A5006094386 @default.
- W4366607162 hasAuthorship W4366607162A5007108734 @default.
- W4366607162 hasAuthorship W4366607162A5009277330 @default.
- W4366607162 hasAuthorship W4366607162A5038143691 @default.
- W4366607162 hasAuthorship W4366607162A5051959933 @default.
- W4366607162 hasAuthorship W4366607162A5056788729 @default.
- W4366607162 hasAuthorship W4366607162A5070942311 @default.
- W4366607162 hasAuthorship W4366607162A5076498328 @default.