Combination therapy including CpG oligodeoxynucleotides and entecavir induces early viral response and enhanced inhibition of viral replication in a woodchuck model of chronic hepadnaviral infection

2016 ◽  
Vol 125 ◽  
pp. 14-24 ◽  
Author(s):  
Zhongji Meng ◽  
Xiaoyong Zhang ◽  
Rongjuan Pei ◽  
Ejuan Zhang ◽  
Thekla Kemper ◽  
...  
2021 ◽  
Vol 9 (2) ◽  
pp. 307
Author(s):  
Evelyn J. Franco ◽  
Xun Tao ◽  
Kaley C. Hanrahan ◽  
Jieqiang Zhou ◽  
Jürgen B. Bulitta ◽  
...  

Chikungunya virus (CHIKV) is an alphavirus associated with a broad tissue tropism for which no antivirals or vaccines are approved. This study evaluated the antiviral potential of favipiravir (FAV), interferon-alpha (IFN), and ribavirin (RBV) against CHIKV as mono- and combination-therapy in cell lines that are clinically relevant to human infection. Cells derived from human connective tissue (HT-1080), neurons (SK-N-MC), and skin (HFF-1) were infected with CHIKV and treated with different concentrations of FAV, IFN, or RBV. Viral supernatant was sampled daily and the burden was quantified by plaque assay on Vero cells. FAV and IFN were the most effective against CHIKV on various cell lines, suppressing the viral burden at clinically achievable concentrations; although the degree of antiviral activity was heavily influenced by cell type. RBV was not effective and demonstrated substantial toxicity, indicating that it is not a feasible candidate for CHIKV. The combination of FAV and IFN was then assessed on all cell lines. Combination therapy enhanced antiviral activity in HT-1080 and SK-N-MC cells, but not in HFF-1 cells. We developed a pharmacokinetic/pharmacodynamic model that described the viral burden and inhibitory antiviral effect. Simulations from this model predicted clinically relevant concentrations of FAV plus IFN completely suppressed CHIKV replication in HT-1080 cells, and considerably slowed down the rate of viral replication in SK-N-MC cells. The model predicted substantial inhibition of viral replication by clinical IFN regimens in HFF-1 cells. Our results highlight the antiviral potential of FAV and IFN combination regimens against CHIKV in clinically relevant cell types.


Kanzo ◽  
2011 ◽  
Vol 52 (1) ◽  
pp. 26-35
Author(s):  
Keisuke Shiina ◽  
Atsushi Naganuma ◽  
Tomofumi Takakusaki ◽  
Masashi Namikawa ◽  
Hiroki Tahara ◽  
...  

2015 ◽  
Vol 99 (10) ◽  
pp. 2124-2131 ◽  
Author(s):  
Nassim Kamar ◽  
Sebastien Lhomme ◽  
Florence Abravanel ◽  
Olivier Cointault ◽  
Laure Esposito ◽  
...  

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