A guinea pig model of Zika virus infection

AbstractThe recent outbreaks of the Ebola virus (EBOV) in Africa have brought global visibility to the shortage of available therapeutic options to treat patients infected with this or closely related viruses. We have recently computationally identified three molecules which have all demonstrated statistically significant efficacy in the mouse model of infection with mouse adapted Ebola virus (ma-EBOV). One of these molecules is the antimalarial pyronaridine tetraphosphate (IC50 range of 0.82-1.30 µM against three strains of EBOV and IC50 range of 1.01-2.72 µM against two strains of Marburg virus (MARV)) which is an approved drug in the European Union and used in combination with artesunate. To date, no small molecule drugs have shown statistically significant efficacy in the guinea pig model of EBOV infection. Pharmacokinetics and range-finding studies in guinea pigs directed us to a single 300mg/kg or 600mg/kg oral dose of pyronaridine 1hr after infection. Pyronaridine resulted in statistically significant survival of 40% at 300mg/kg and protected from a lethal challenge with EBOV. In comparison, oral favipiravir (300 mg/kg dosed once a day) had 43.5 % survival. The in vitro metabolism and metabolite identification of pyronaridine and another of our EBOV active molecules, tilorone, which suggests significant species differences which may account for the efficacy or lack thereof, respectively in guinea pig. In summary, our studies with pyronaridine demonstrates its utility for repurposing as an antiviral against EBOV and MARV, providing justification for future testing in non-human primates.ImportanceThere is currently no antiviral small molecule drug approved for treating Ebola Virus infection. We have previously used machine learning models to identify new uses for approved drugs and demonstrated their activity against the Ebola virus in vitro and in vivo. We now describe the pharmacokinetic properties of the antimalarial pyronaridine in the guinea pig. In addition, we show that this drug is effective against multiple strains of EBOV and MARV in vitro and in the guinea pig model of Ebola virus infection. These combined efforts indicate the need to further test this molecule in larger animal efficacy studies prior to clinical use in humans. These findings also may be useful for repurposing this drug for use against other viruses in future.

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Favipiravir (T-705) Inhibits Junín Virus Infection and Reduces Mortality in a Guinea Pig Model of Argentine Hemorrhagic Fever

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0002614 ◽

2013 ◽

Vol 7 (12) ◽

pp. e2614 ◽

Cited By ~ 52

Author(s):

Brian B. Gowen ◽

Terry L. Juelich ◽

Eric J. Sefing ◽

Trevor Brasel ◽

Jennifer K. Smith ◽

...

Keyword(s):

Virus Infection ◽

Guinea Pig ◽

Hemorrhagic Fever ◽

Pig Model ◽

Junin Virus ◽

Argentine Hemorrhagic Fever ◽

Guinea Pig Model ◽

Junín Virus

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Use of a Scalable Replicon-Particle Vaccine to Protect Against Lethal Lassa Virus Infection in the Guinea Pig Model

The Journal of Infectious Diseases ◽

10.1093/infdis/jiy123 ◽

2018 ◽

Vol 217 (12) ◽

pp. 1957-1966 ◽

Cited By ~ 12

Author(s):

Markus H Kainulainen ◽

Jessica R Spengler ◽

Stephen R Welch ◽

JoAnn D Coleman-McCray ◽

Jessica R Harmon ◽

...

Keyword(s):

Virus Infection ◽

Guinea Pig ◽

Pig Model ◽

Lassa Virus ◽

Replicon Particle ◽

Guinea Pig Model

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Defibrillation and the upper limit of vulnerability to fibrillation in a transthoracic Guinea pig model*1

Journal of Cardiothoracic and Vascular Anesthesia ◽

10.1016/s1053-0770(99)90052-6 ◽

1999 ◽

Vol 32 (2) ◽

pp. 159-166

Author(s):

H LI

Keyword(s):

Guinea Pig ◽

Pig Model ◽

Upper Limit ◽

Upper Limit Of Vulnerability ◽

Guinea Pig Model

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Effect of troglitazone, an inducer of the peroxisome proliferator-activated receptor γ (PPARγ), on uterine leiomyoma development in the guinea pig model

Journal of the Society for Gynecologic Investigation ◽

10.1016/s1071-5576(97)86654-3 ◽

1998 ◽

Vol 5 (1) ◽

pp. 180A-180A

Author(s):

J TSIBRIS ◽

K PORTER ◽

A JAZAYERI ◽

S NICOSIA ◽

G PORTER ◽

...

Keyword(s):

Guinea Pig ◽

Uterine Leiomyoma ◽

Pig Model ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Guinea Pig Model

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Congenital Zika Virus Infection Paradigm: What is in the Wardrobe? A Narrative Review

East Africa Science ◽

10.24248/easci.v1i1.4 ◽

2019 ◽

Vol 1 (1) ◽

pp. 49-56

Author(s):

Mariam M. Mirambo ◽

Lucas Matemba ◽

Mtebe Majigo ◽

Stephen E. Mshana

Keyword(s):

Virus Infection ◽

Neural Tube ◽

Zika Virus ◽

English Language ◽

Case Reports ◽

Case Series ◽

Epidemiological Studies ◽

Ocular Manifestations ◽

Zika Virus Infection ◽

N 93

Background: Zika virus infection during pregnancy has been recently associated with congenital microcephaly and other severe neural tube defects. However, the magnitude of confirmed cases and the scope of these anomalies have not been extensively documented. This review focuses on the magnitude of laboratory-confirmed congenital Zika virus cases among probable cases and describing the patterns of congenital anomalies allegedly caused by the Zika virus, information which will inform further research in this area. Methods: We conducted a literature search for English-language articles about congenital Zika virus infection using online electronic databases (PubMed/MEDLINE, POPLINE, Embase, Google Scholar, and Web of Knowledge). The search terms used were, “zika”, “pregnancy”, [year], “microcephaly”, “infants”, “children”, “neonates”, “foetuses”, “neural tube defect”, and “CNS manifestations” in different combinations. All articles reporting cases or case series between January 2015 and December 2016 were included. Data were entered into a Microsoft Excel database and analysed to obtain proportions of the confirmed cases and patterns of anomalies. Results: A total of 24 articles (11 case series, 9 case reports, and 4 others) were found to be eligible and included in this review. These articles reported 919 cases, with or without microcephaly, presumed to have congenital Zika virus infection. Of these cases, 884 (96.2%) had microcephaly. Of the 884 cases of microcephaly, 783 (88.6%) were tested for Zika virus infection, and 216 (27.6%; 95% confidence interval, 24.5% to 30.8%) were confirmed to be Zika virus-positive. In addition to microcephaly, other common abnormalities reported – out of 442 cases investigated – were calcifications of brain tissue (n=240, 54.3%), ventriculomegaly (n=93, 20.8%), cerebellar hypoplasia (n=52, 11.7%), and ocular manifestations (n=46, 10.4%). Conclusion: Based on the available literature, Zika virus infection during pregnancy might lead to a wide array of outcomes other than microcephaly. There is a need for more epidemiological studies in Zika-endemic areas, particularly in Africa, to ascertain the role of Zika virus in causing congenital neurological defects.

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Congenital Zika Virus Infection Paradigm: What is in the Wardrobe? A Narrative Review

East Africa Science ◽

10.24248/easci.v1.iss1.4 ◽

2019 ◽

Vol 1 (1) ◽

pp. 49-56

Author(s):

Mariam M. Mirambo ◽

Lucas Matemba ◽

Mtebe Majigo ◽

Stephen E. Mshana

Keyword(s):

Virus Infection ◽

Neural Tube ◽

Zika Virus ◽

English Language ◽

Case Reports ◽

Case Series ◽

Epidemiological Studies ◽

Ocular Manifestations ◽

Zika Virus Infection ◽

N 93

Background: Zika virus infection during pregnancy has been recently associated with congenital microcephaly and other severe neural tube defects. However, the magnitude of confirmed cases and the scope of these anomalies have not been extensively documented. This review focuses on the magnitude of laboratory-confirmed congenital Zika virus cases among probable cases and describing the patterns of congenital anomalies allegedly caused by the Zika virus, information which will inform further research in this area. Methods: We conducted a literature search for English-language articles about congenital Zika virus infection using online electronic databases (PubMed/MEDLINE, POPLINE, Embase, Google Scholar, and Web of Knowledge). The search terms used were, “zika”, “pregnancy”, [year], “microcephaly”, “infants”, “children”, “neonates”, “foetuses”, “neural tube defect”, and “CNS manifestations” in different combinations. All articles reporting cases or case series between January 2015 and December 2016 were included. Data were entered into a Microsoft Excel database and analysed to obtain proportions of the confirmed cases and patterns of anomalies. Results: A total of 24 articles (11 case series, 9 case reports, and 4 others) were found to be eligible and included in this review. These articles reported 919 cases, with or without microcephaly, presumed to have congenital Zika virus infection. Of these cases, 884 (96.2%) had microcephaly. Of the 884 cases of microcephaly, 783 (88.6%) were tested for Zika virus infection, and 216 (27.6%; 95% confidence interval, 24.5% to 30.8%) were confirmed to be Zika virus-positive. In addition to microcephaly, other common abnormalities reported – out of 442 cases investigated – were calcifications of brain tissue (n=240, 54.3%), ventriculomegaly (n=93, 20.8%), cerebellar hypoplasia (n=52, 11.7%), and ocular manifestations (n=46, 10.4%). Conclusion: Based on the available literature, Zika virus infection during pregnancy might lead to a wide array of outcomes other than microcephaly. There is a need for more epidemiological studies in Zika-endemic areas, particularly in Africa, to ascertain the role of Zika virus in causing congenital neurological defects.

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