PubMed artikkelin mainitsema Rocaglamidi , translaatioinhibiittori , kohteena ULK-1, autofagiainitiaattori

Tässä flavagliinien joukosta  saattaa olla jotain koronaviruksen vastaista, koska koronavirus COVID-19 saattaa alkuun autofagia koneiston, mutta vain alkuun eikä loppuun asti, sillä se käyttää sitä koneistoa virioninsa  tehokkaaseen valmistukseen ja sitten lähettää ne eteenpäin  keskeyttäen autofagiatien jonkin ajan päästä.. 

https://en.wikipedia.org/wiki/Rocaglamide
Rocaglamide is a natural product which belongs to a class of molecules called flavaglines.^[1][2] This compound was isolated in 1982 by King and colleagues based on its antileukemic activity.^[3] Like other flavaglines, rocaglamide displays potent insecticidal, antifungal, anti-inflammatory and anticancer activities. Rocaglamide A (RocA) inhibits eukaryotic translation initiation by binding to the translation initiation factor eIF4A and converting it into a translational repressor.^[4]
Rocaglamide was first synthesized by Barry Trost in 1990.^[5] Although other syntheses have been described since, Trost’s remains the only one to afford rocaglamide in an enantio-specific manner.
 See also

• FL3 (flavagline)
• Eukaryotic translation
• eIF4A
• SilvestrolSilvestrol is a natural product from the flavagline family, with a cyclopenta[b]benzofuran core structure and an unusual dioxane ether side chain, which is found in the bark of trees from the genus Aglaia, especially Aglaia silvestris and Aglaia foveolata.^[1]
  BioactivityIt acts as a potent and selective inhibitor of the RNA helicase enzyme eIF4A, and has both broad-spectrum antiviral activity against diseases such as Ebola and coronaviruses,,^[2][3][4][5] and anti-cancer properties,^[6][7] which makes it of considerable interest in medical research. However, as it cannot be extracted from tree bark in commercial amounts and is prohibitively complex to produce synthetically,^[8] practical applications have focused more on structurally simplified analogues such as CR-31-B.^[9]

PubMed tieto:

Autophagy. 2018;14(10):1831-1844. doi: 10.1080/15548627.2018.1489946. Epub 2018 Aug 17.

Rocaglamide enhances NK cell-mediated killing of non-small cell lung cancer cells by inhibiting autophagy.

Yao C^1,2, Ni Z^1,2, Gong C¹, Zhu X¹, Wang L², Xu Z³, Zhou C⁴, Li S⁴, Zhou W⁵, Zou C³, Zhu S^1,2.Abstract

Targeting macroautophagy/autophagy is a novel strategy in cancer immunotherapy. In the present study, we showed that the natural product rocaglamide (RocA) enhanced natural killer (NK) cell-mediated lysis of non-small cell lung cancer (NSCLC) cells in vitro and tumor regression in vivo. Moreover, this effect was not related to the NK cell recognition of target cells or expressions of death receptors. Instead, RocA inhibited autophagy and restored the level of NK cell-derived GZMB (granzyme B) in NSCLC cells, therefore increasing their susceptibility to NK cell-mediated killing. In addition, we further identified that the target of RocA was ULK1 (unc-51 like autophagy activating kinase 1) that is required for autophagy initiation. Using firefly luciferase containing the 5´ untranslated region of ULK1, we found that RocA inhibited the protein translation of ULK1 in a sequence-specific manner. Taken together, RocA could block autophagic immune resistance to NK cell-mediated killing, and our data suggested that RocA was a promising therapeutic candidate in NK cell-based cancer immunotherapy.KEYWORDS:

Autophagy; cancer immunotherapy; immune resistance; natural killer cells; non-small cell lung cancer; rocaglamide

PMID:

29969944

PMCID:

PMC6135631

DOI:

10.1080/15548627.2018.1489946

[Indexed for MEDLINE]

Free PMC Article