In vitro antiviral activity and underlying molecular mechanisms of dipotassium glycyrrhetate against porcine reproductive and respiratory syndrome virus

2013 ◽  
Vol 18 (8) ◽  
pp. 997-1004 ◽  
Author(s):  
Zhi-Wei Wang ◽  
Na Sun ◽  
Cai-Hong Wu ◽  
Jun-Bing Jiang ◽  
Yuan-Sheng Bai ◽  
...  
2020 ◽  
Author(s):  
Juhee Son ◽  
Shimeng Huang ◽  
Qiru Zeng ◽  
Traci L. Bricker ◽  
James Brett Case ◽  
...  

AbstractPathogenic coronaviruses represent a major threat to global public health. Here, using a recombinant reporter virus-based compound screening approach, we identified several small-molecule inhibitors that potently block the replication of the newly emerged severe acute respiratory syndrome virus 2 (SARS-CoV-2). Two compounds, nitazoxanide and JIB-04 inhibited SARS-CoV-2 replication in Vero E6 cells with an EC50 of 4.90 μM and 0.69 μM, respectively, with specificity indices of greater than 150. Both inhibitors had in vitro antiviral activity in multiple cell types against some DNA and RNA viruses, including porcine transmissible gastroenteritis virus. In an in vivo porcine model of coronavirus infection, administration of JIB-04 reduced virus infection and associated tissue pathology, which resulted in improved body weight gain and survival. These results highlight the potential utility of nitazoxanide and JIB-04 as antiviral agents against SARS-CoV-2 and other viral pathogens.


Virology ◽  
2012 ◽  
Vol 432 (1) ◽  
pp. 73-80 ◽  
Author(s):  
Ke Liu ◽  
Xiuli Feng ◽  
Zhiyong Ma ◽  
Chao Luo ◽  
Bin Zhou ◽  
...  

2016 ◽  
Vol 161 (7) ◽  
pp. 1883-1890 ◽  
Author(s):  
Lan Li ◽  
Qisheng Zheng ◽  
Yuanpeng Zhang ◽  
Pengcheng Li ◽  
Yanfeng Fu ◽  
...  

2003 ◽  
Vol 77 (6) ◽  
pp. 3702-3711 ◽  
Author(s):  
H. S. Nielsen ◽  
G. Liu ◽  
J. Nielsen ◽  
M. B. Oleksiewicz ◽  
A. Bøtner ◽  
...  

ABSTRACT A full-length cDNA clone of the prototypical North American porcine reproductive and respiratory syndrome virus (PRRSV) isolate VR-2332 was assembled in the plasmid vector pOK12. To rescue infectious virus, capped RNA was transcribed in vitro from the pOK12 clone and transfected into BHK-21C cells. The supernatant from transfected monolayers were serially passaged on Marc-145 cells and porcine pulmonary alveolar macrophages. Infectious PRRSV was recovered on Marc-145 cells as well as porcine pulmonary macrophages; thus, the cloned virus exhibited the same cell tropism as the parental VR-2332 strain. However, the cloned virus was clearly distinguishable from the parental VR-2332 strain by an engineered marker, a BstZ17I restriction site. The full-length cDNA clone had 11 nucleotide changes, 2 of which affected coding, compared to the parental VR-2332 strain. Additionally, the transcribed RNA had an extra G at the 5′ end. To examine whether these changes influenced viral replication, we examined the growth kinetics of the cloned virus in vitro. In Marc-145 cells, the growth kinetics of the cloned virus reflected those of the parental isolate, even though the titers of the cloned virus were consistently slightly lower. In experimentally infected 5.5-week-old pigs, the cloned virus produced blue discoloration of the ears, a classical clinical symptom of PRRSV. Also, the seroconversion kinetics of pigs infected with the cloned virus and VR-2332 were very similar. Hence, virus derived from the full-length cDNA clone appeared to recapitulate the biological properties of the highly virulent parental VR-2332 strain. This is the first report of an infectious cDNA clone based on American-type PRRSV. The availability of this cDNA clone will allow examination of the molecular mechanisms behind PRRSV virulence and attenuation, which might in turn allow the production of second-generation, genetically engineered PRRSV vaccines.


2020 ◽  
Vol 16 (1) ◽  
Author(s):  
Chaiwat Arjin ◽  
Kidsadagon Pringproa ◽  
Surat Hongsibsong ◽  
Warintorn Ruksiriwanich ◽  
Mintra Seel-audom ◽  
...  

2016 ◽  
Vol 73 (3) ◽  
pp. 317-323 ◽  
Author(s):  
Jiaping Feng ◽  
Xiaolei Bai ◽  
Tiantian Cui ◽  
Han Zhou ◽  
Yao Chen ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Li Du ◽  
Honglei Wang ◽  
Fang Liu ◽  
Zeyu Wei ◽  
Changjiang Weng ◽  
...  

In 2006, atypical porcine reproductive and respiratory syndrome (PRRS) caused by a highly pathogenic PRRSV (HP-PRRSV) strain broke out in China. Atypical PRRS is characterized by extremely high fever and high mortality in pigs of all ages. Prostaglandin E2 (PGE2) derived from arachidonic acid through the activation of the rate-limiting enzyme cyclooxygenase type 1/2 (COX-1/2) plays an important role in fever. Here, we showed that HP-PRRSV infection increased PGE2 production in microglia via COX-2 up-regulation depending on the activation of MEK1-ERK1/2-C/EBPβ signaling pathways. Then, we screened HP-PRRSV proteins and demonstrated that HP-PRRSV nonstructural protein 2 (NSP2) activated MEK1-ERK1/2-C/EBPβ signaling pathways by interacting with 14-3-3ζ to promote COX-2 expression, leading to PGE2 production. Furthermore, we identified that the amino acid residues 500-596 and 658-777 in HP-PRRSV NSP2 were essential to up-regulate COX-2 expression and PGE2 production. Finally, we made mutant HP-PRRS viruses with the deletion of residues 500-596 and/or 658-777, and found out that these viruses had impaired ability to up-regulate COX-2 and PGE2 production in vitro and in vivo. Importantly, pigs infected with the mutant viruses had relieved fever, clinical symptoms, and mortality. These data might help us understand the molecular mechanisms underlying the high fever and provide clues for the development of HP-PRRSV attenuated vaccines.


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