Summary. -Effects of a polysacharide from Chinese herbal plant Astragalus membranaceus (APS) on the expression of Epstein-Barr virus (EBV) immediate early proteins Zta, Rta and EA-D in Raji cells were examined. EBV switch from latent to lytic cycle in Raji cells was induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) and sorbol butyrate (SB) and the effects of APS were examined by immunofluorescence, western blotting and flow cytometry. APS in a non-cytotoxic concentration of 30 μg/ml significantly suppressed the expression of Zta, Rta and EA-D during the EBV lytic cycle. Our observations indicate that APS is potentially useful as an anti-EBV drug.
Africa and in its aftermath, the passive administration of monoclonal antibodies (mAbs) emerged as a promising treatment approach [1][2][3][4][5][6][7] . However, all antibody-based therapeutics currently in advanced development are specific for a single member of the Ebolavirus genus, Ebola virus (EBOV), and ineffective against divergent outbreak-causing ebolaviruses, including Bundibugyo virus (BDBV) and Sudan virus (SUDV) 2,3,5,7 . Here we advance MBP134, a cocktail of two broadly neutralizing human mAbs targeting the filovirus surface glycoprotein, GP, as a candidate pan-ebolavirus therapeutic. One component of this cocktail is a pan-ebolavirus neutralizing mAb, ADI-15878, isolated from a human EVD survivor 8,9 . The second, ADI-23774, was derived by affinity maturation of a human mAb 8,9 via yeast display to enhance its potency against SUDV. MBP134 afforded exceptionally potent pan-ebolavirus neutralization in vitro and demonstrated greater protective efficacy than ADI-15878 alone in the guinea pig model of lethal EBOV challenge.A second-generation cocktail, MBP134 AF , engineered to effectively harness natural killer (NK) cells afforded additional, unprecedented improvements in protective efficacy against EBOV and SUDV in guinea pigs relative to both its precursor and to any mAbs or mAb cocktails tested previously. MBP134 AF is a best-in-class mAb cocktail suitable for evaluation as a pan-ebolavirus therapeutic in nonhuman primates.We previously isolated and characterized 349 GP-specific mAbs from a survivor of the West African EVD epidemic 9 . A systematic analysis of this library for breadth of the neutralizing mAb response against ebolaviruses identified ADI-15878 as a promising candidate therapeutic 8 .ADI-15878 possesses potent pan-ebolavirus neutralizing activity through its recognition of a 2
Filoviruses such as Ebola virus (EBOV), Marburg virus (MARV), and Sudan virus (SUDV) cause deadly viral hemorrhagic fever in humans, with high case-fatality rates; however, no licensed therapeutic agent or vaccine has been clinically approved to treat or prevent infection. T-705 (favipiravir) is a novel antiviral drug that has been approved for the treatment of influenza in Japan. T-705 exhibits broad-spectrum antiviral activity against different viruses, including MARV and EBOV, and here, we are the first to report the in vitro and in vivo antiviral activity of T-705 against SUDV. T-705 treatment reduced SUDV replication in Vero E6 cells. Subcutaneous administration of T-705, beginning 1-4 days after infection and continuing for 7 days, significantly protected SUDV-infected guinea pigs, with a survival rate of 83%-100%. Viral RNA replication and infectious virus production were also significantly reduced in the blood, spleen, liver, lungs, and kidney. Moreover, early administration of low-dose T-705 and late administration (at 5 days after infection) of higher-dose T-705 also showed partial protection. Overall, our study is the first to demonstrate the antiviral activity of T-705 against SUDV, suggesting that T-705 may be a potential drug candidate for use during outbreaks.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.