scholarly journals A direct-acting antiviral drug abrogates viremia in Zika virus–infected rhesus macaques

2020 ◽  
Vol 12 (547) ◽  
pp. eaau9135 ◽  
Author(s):  
So-Yon Lim ◽  
Christa E. Osuna ◽  
Katharine Best ◽  
Ray Taylor ◽  
Elsa Chen ◽  
...  
Keyword(s):  
Virus Infection ◽  
Zika Virus ◽  
Rhesus Macaques ◽  
Antiviral Drug ◽  
Neurological Complications ◽  
Direct Acting Antiviral ◽  
Antiviral Efficacy ◽  
Zika Virus Infection ◽  
Dosing Strategies ◽  
Direct Acting

Zika virus infection in humans has been associated with serious reproductive and neurological complications. At present, no protective antiviral drug treatment is available. Here, we describe the testing and evaluation of the antiviral drug, galidesivir, against Zika virus infection in rhesus macaques. We conducted four preclinical studies in rhesus macaques to assess the safety, antiviral efficacy, and dosing strategies for galidesivir (BCX4430) against Zika virus infection. We treated 70 rhesus macaques infected by various routes with the Puerto Rico or Thai Zika virus isolates. We evaluated galidesivir administered as early as 90 min and as late as 72 hours after subcutaneous Zika virus infection and as late as 5 days after intravaginal infection. We evaluated the efficacy of a range of galidesivir doses with endpoints including Zika virus RNA in plasma, saliva, urine, and cerebrospinal fluid. Galidesivir dosing in rhesus macaques was safe and offered postexposure protection against Zika virus infection. Galidesivir exhibited favorable pharmacokinetics with no observed teratogenic effects in rats or rabbits at any dose tested. The antiviral efficacy of galidesivir observed in the blood and central nervous system of infected animals warrants continued evaluation of this compound for the treatment of flaviviral infections.

scholarly journals BCX4430, a Broad-Spectrum Adenosine Analog Direct-Acting Antiviral Drug, Abrogates Viremia in Rhesus Macaques Challenged With Zika Virus

2016 ◽  
Vol 3 (suppl_1) ◽  
Author(s):  
So-Yon Lim ◽  
Christa Osuna ◽  
Ray Taylor ◽  
Amanda Mathis ◽  
Vivek Kamath ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Zika Virus ◽  
Rhesus Macaques ◽  
Antiviral Drug ◽  
Direct Acting Antiviral ◽  
Direct Acting ◽  
Adenosine Analog

scholarly journals Galidesivir, a Direct-Acting Antiviral Drug, Abrogates Viremia in Rhesus Macaques Challenged with Zika Virus

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S55-S55 ◽  
Author(s):  
So-Yon Lim ◽  
Christa Osuna ◽  
Jessica Lakritz ◽  
Elsa Chen ◽  
Gyeol Yoon ◽  
...  
Keyword(s):  
Zika Virus ◽  
Rhesus Macaques ◽  
Antiviral Drug ◽  
Plasma Viremia ◽  
Zikv Infection ◽  
Multiple Endpoints ◽  
Direct Acting Antiviral ◽  
Dosing Strategies ◽  
Complete Blood Counts ◽  
High Level

Abstract Background Zika virus (ZIKV) was first isolated from a sentinel rhesus monkey in 1947. ZIKV infection in humans is associated with serious neurological and reproductive complications. No antiviral or protective vaccine is yet available. Galidesivir an adenosine analog is a potent viral RNA-dependent RNA polymerase inhibitor with demonstrated broad-spectrum antiviral activity. Methods We have conducted four pre-clinical studies in rhesus macaques to assess the safety, antiviral efficacy and dosing strategies of galidesivir against ZIKV infection. Collectively, we have challenged 70 rhesus macaques by various routes using 1x105 TCID50of a Puerto Rican ZIKV isolate. We have evaluated galidesivir therapy administered via IM injection as early as 90 minutes and up to 72 hours after subcutaneous (SC) ZIKV challenge, and as late as 5 days after intravaginal (IVAG) challenge. In these studies, we evaluated the efficacy of a range of loading and maintence doses of galidesivir. The highest dose evaluated has been a loading dose of 100mg/kg BID followed by a maintenance dose of 25mg/kg BID for nine days. We followed multiple endpoints, including ZIKV RNA levels in plasma, urine, saliva, and cerebrospinal fluid. Immune activation, complete blood counts, chemistries and galidesivir pharmacokinetics were also monitored. Results Galidesivir was well-tolerated in all studies. All untreated controls developed high-level plasma viremia, and had readily detectable ZIKV RNA in CSF, saliva and urine post-infection. Animals treated in the first 24 hours after SC ZIKV challenge did not develop plasma viremia and were either negative or had significantly reduced ZIKV RNA in bodily fluids. Animals treated with galidesivir later (up to 72 hours) were partially protected; they had detectable plasma ZIKV RNA, but the onset was delayed and/or magnitude significantly reduced compared with controls. Animals infected IVAG were protected by galidesivir treatment up until day 5 after infection, with no blood viremia and significant reductions in ZIKV RNA in the CSF as compared with controls. Conclusion Galidesivir dosing in rhesus macaques was well-tolerated and offered significant protection against ZIKV infection. These results warrant continued study and clinical evaluation. Disclosures R. Taylor, BioCryst Pharmaceuticals: Employee, Salary; S. MacLennan, BioCryst: Employee, Salary; M. Leonard, BioCryst: Employee, Salary; E. Giuliano, BioCryst: Employee, Salary; A. Mathis, BioCryst Pharmaceuticals: Employee, Salary; E. Berger, BioCryst: Employee, Salary; Y. Babu, BioCryst: Employee, Salary; W. Sheridan, BioCryst Pharmaceuticals: Employee, Salary

The P-MAPA immunomodulator partially prevents apoptosis induced by Zika virus infection in THP-1 cells

2020 ◽  
Vol 21 ◽  
Author(s):  
Morganna C. Lima ◽  
Elisa A. N. Azevedo ◽  
Clarice N. L. de Morais ◽  
Larissa I. O. de Sousa ◽  
Bruno M. Carvalho ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Death ◽  
Virus Infection ◽  
Virus Replication ◽  
Zika Virus ◽  
Mammalian Cells ◽  
Caspase 3 ◽  
Neurological Complications ◽  
Zika Virus Infection

Background: Zika virus is an emerging arbovirus of global importance. ZIKV infection is associated with a range of neurological complications such as the Congenital Zika Syndrome and Guillain Barré Syndrome. Despite the magnitude of recent outbreaks, there is no specific therapy to prevent or to alleviate disease pathology. Objective: To investigate the role of P-MAPA immunomodulator in Zika-infected THP-1 cells. Methods: THP-1 cells were subjected at Zika virus infection (Multiplicity of Infection = 0.5) followed by treatment with P-MAPA for until 96 hours post-infection. After that, the cell death was analyzed by annexin+/ PI+ and caspase 3/ 7+ staining by flow cytometry. In addition, the virus replication and cell proliferation were accessed by RT-qPCR and Ki67 staining, respectively. Results: We demonstrate that P-MAPA in vitro treatment significantly reduces Zika virus-induced cell death and caspase-3/7 activation on THP-1 infected cells, albeit it has no role in virus replication and cell proliferation. Conclusions: Our study reveals that P-MAPA seems to be a satisfactory alternative to inhibits the effects of Zika virus infection in mammalian cells.

Neurological Complications of Congenital Zika Virus Infection

2019 ◽  
Vol 91 ◽  
pp. 3-10 ◽  
Author(s):  
Vinícius de Melo Marques ◽  
Camilla Sousa Santos ◽  
Isabella Godinho Santiago ◽  
Solomar Martins Marques ◽  
Maria das Graças Nunes Brasil ◽  
...  
Keyword(s):  
Virus Infection ◽  
Zika Virus ◽  
Neurological Complications ◽  
Zika Virus Infection

scholarly journals Zika virus infection in pregnant rhesus macaques causes placental dysfunction and immunopathology

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Alec J. Hirsch ◽  
Victoria H. J. Roberts ◽  
Peta L. Grigsby ◽  
Nicole Haese ◽  
Matthias C. Schabel ◽  
...  
Keyword(s):  
Virus Infection ◽  
Zika Virus ◽  
Rhesus Macaques ◽  
Placental Dysfunction ◽  
Zika Virus Infection

Seroprevalence of Zika virus in selected regions in Kenya

2019 ◽  
Vol 113 (12) ◽  
pp. 735-739 ◽  
Author(s):  
Bramuel Kisuya ◽  
Moses M Masika ◽  
Esto Bahizire ◽  
Julius O Oyugi
Keyword(s):  
Virus Infection ◽  
Zika Virus ◽  
Healthy Adult ◽  
Neurological Complications ◽  
Previous Exposure ◽  
Limited Data ◽  
Zika Virus Infection ◽  
Human Sera ◽  
Study Population ◽  
The University

Abstract Background The Zika virus pandemic in South America in 2015–2016 and the association of Zika virus infection with neurological complications such as microcephaly in newborns distressed the global community. There is limited data on the prevalence of Zika virus in Kenya despite evidence of its circulation in East Africa. This study aimed at assessing the seroprevalence of Zika virus in selected areas in Kenya. Methods Healthy adult human sera originally collected from Nairobi, Eldoret and Kisumu from 2009 to 2014 and archived at the University of Nairobi laboratories were examined for Zika virus antibodies. An IgG-based ELISA was used to screen 577 sera. Any serum tested positive by ELISA was confirmed for Zika virus infection by plaque reduction neutralization test (PRNT). Results The seroprevalence of Zika virus in the study population was about 0.2 % (1/577) as confirmed by PRNT. Additionally, three sera that were false positive by ELISA for Zika virus were confirmed as positive for dengue virus by PRNT. Conclusion There was evidence of low previous exposure to Zika virus in the study population. Of the three regions in Kenya where sera for this study were obtained, only Kisumu County had one case of previous exposure to Zika virus.

scholarly journals Impact of prior flavivirus immunity on Zika virus infection in rhesus macaques

2017 ◽  
Vol 13 (8) ◽  
pp. e1006487 ◽  
Author(s):  
Michael K. McCracken ◽  
Gregory D. Gromowski ◽  
Heather L. Friberg ◽  
Xiaoxu Lin ◽  
Peter Abbink ◽  
...  
Keyword(s):  
Virus Infection ◽  
Zika Virus ◽  
Rhesus Macaques ◽  
Zika Virus Infection

scholarly journals Zika Virus infection of rhesus macaques leads to viral persistence in multiple tissues

2017 ◽  
Vol 13 (3) ◽  
pp. e1006219 ◽  
Author(s):  
Alec J. Hirsch ◽  
Jessica L. Smith ◽  
Nicole N. Haese ◽  
Rebecca M. Broeckel ◽  
Christopher J. Parkins ◽  
...  
Keyword(s):  
Virus Infection ◽  
Zika Virus ◽  
Rhesus Macaques ◽  
Viral Persistence ◽  
Zika Virus Infection
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