A sensitive virus yield assay for evaluation of Antivirals against Zika Virus

Goebel, Scott J.; Snyder, Beth; Sellati, Timothy J.; Saeed, Mohammad; Ptak, Roger G.; Murray, Michael G.; Bostwick, Robert; Rayner, Jonathan O.; Koide, Fusataka; Kalkeri, Raj

doi:10.1016/j.jviromet.2016.09.015

Cited by 37 publications

(49 citation statements)

References 30 publications

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“…While the test with highest specificity and sensitivity to detect ZIKV-infected patients is reverse-transcriptase polymerase chain reaction (RT-PCR), which detects the presence of ZIKV RNA in human body fluid samples [37, 38], the use of this method is limited as ZIKV can only be reliably detected in up to the first 7 days after infection [5, 32]. RT-PCR is expensive and samples must be sent to specialized laboratories for analysis, which are not yet readily accessible in all countries affected by ZIKV.…”

Section: Findings and Discussionmentioning

confidence: 99%

Risk of bias and confounding of observational studies of Zika virus infection: A scoping review of research protocols

et al. 2017

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IntroductionGiven the severity and impact of the current Zika virus (ZIKV) outbreak in the Americas, numerous countries have rushed to develop research studies to assess ZIKV and its potential health consequences. In an effort to ensure that studies are comprehensive, both internally and externally valid, and with reliable results, the World Health Organization, the Pan American Health Organization, Institut Pasteur, the networks of Fiocruz, the Consortia for the Standardization of Influenza Seroepidemiology (CONSISE) and the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) have generated six standardized clinical and epidemiological research protocols and questionnaires to address key public health questions on ZIKV.MethodsWe conducted a systematic search of ongoing study protocols related to ZIKV research. We analyzed the content of protocols of 32 cohort studies and 13 case control studies for systematic bias that could produce erroneous results. Additionally we aimed to characterize the risks of bias and confounding in observational studies related to ZIKV and to propose ways to minimize them, including the use of six newly standardized research protocols.ResultsObservational studies of ZIKV face an array of challenges, including measurement of exposure and outcomes (microcephaly and Guillain-Barré Syndrome). Potential confounders need to be measured where known and controlled for in the analysis. Selection bias due to non-random selection is a significant issue, particularly in the case-control design, and losses to follow-up is equally important for the cohort design.ConclusionObservational research seeking to answer key questions on the ZIKV should consider these restrictions and take precautions to minimize bias in an effort to provide reliable and valid results. Utilization of the standardized research protocols developed by the WHO, PAHO, Institut Pasteur, and CONSISE will harmonize the key methodological aspects of each study design to minimize bias at different stages of the study. Biases need to be considered by researchers implementing the standardized protocols as well as by users of observational epidemiological studies of ZIKV.

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Section: Findings and Discussionmentioning

confidence: 99%

Risk of bias and confounding of observational studies of Zika virus infection: A scoping review of research protocols

et al. 2017

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“…[4,5,[20][21][22]. Anti ZIKV drugs inhibit ZIKV entry into cells [23][24][25]; inhibit viral replication targeting NS3 protein [26], NS5 protein [27], NS2B-NS3 protease [28], or nucleoside biosynthesis [29].…”

Section: Discussionmentioning

confidence: 99%

Azithromycin Inhibits the Replication of Zika Virus

Bosseboeuf¹,

Aubry²,

Nhan³

et al. 2018

J Antivir Antiretrovir

114

100

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Background: The emergence of Zika virus (ZIKV) is associated to dramatic complications in fetuses and neonates. As there is no vaccine and no drug to prevent and treat ZIKV infections, there is an urgent need to have active drugs against ZIKV that can be used during pregnancy. Large screening strategies suggested that azithromycin (AZ) has an in vitro activity against ZIKV, we provide additional data supporting this hypothesis.

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“…Primer and probe sequences are provided in Goebel et al (2016). Primer and probe sequences were characterized for compatible melting temperatures (Tm), self-dimer and hairpin potential using the Integrated DNA Technologies (IDT, Coralville, IA) “Primer Analysis software” tool.…”

Section: Methodsmentioning

confidence: 99%

“…The probe has a 5′ 6-FAM reporter and an internal (9th position) ZEN quencher and a 3′ IBFQ Iowa black quencher. Primers and protocols used for the generation of the RNA template used for the standard curve for absolute quantitation were as described in Goebel et al (2016).…”

Section: Methodsmentioning

confidence: 99%

Development of a Zika Virus Infection Model in Cynomolgus Macaques

et al. 2016

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Limited availability of Indian rhesus macaques (IRM) is a bottleneck to study Zika virus (ZIKV) pathogenesis and evaluation of appropriate control measures in non-human primates. To address these issues, we report here the Mauritian cynomolgus macaque (MCM) model for ZIKV infection. In brief, six MCMs (seronegative for Dengue and ZIKV) were subdivided into three cohorts with a male and female each and challenged with different doses of Asian [PRVABC59 (Puerto Rico) or FSS13025 (Cambodia)] or African (IBH30656) lineage ZIKV isolates. Clinical signs were monitored; and biological fluids (serum, saliva, and urine) and tissues (testes and brain) were assessed for viral load by quantitative reverse transcription polymerase chain reaction and neutralizing antibodies (Nab) by 50% Plaque Reduction Neutralization Test (PRNT50) at various times post-infection (p.i). PRVABC59 induced viremia detectable up to day 10, with peak viral load at 2–3 days p.i. An intermittent viremia spike was observed on day 30 with titers reaching 2.5 × 103 genomes/mL. Moderate viral load was observed in testes, urine and saliva. In contrast, FSS13025 induced viremia lasting only up to 6 days and detectable viral loads in testes but not in urine and saliva. Recurrent viremia was detected but at lower titers compare to PRVABC59. Challenge with either PRVABC59 or FSS13025 resulted in 100% seroconversion; with mean PRNT50 titers ranging from 597 to 5179. IBH30656 failed to establish infection in MCM suggesting that MCM are susceptible to infection with ZIKV isolates of the Asian lineage but not from Africa. Due to the similarity of biphasic viremia and Nab responses between MCM and IRM models, MCM could be a suitable alternative for evaluation of ZIKV vaccine and therapeutic candidates.

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A sensitive virus yield assay for evaluation of Antivirals against Zika Virus

Cited by 37 publications

References 30 publications

Risk of bias and confounding of observational studies of Zika virus infection: A scoping review of research protocols

Risk of bias and confounding of observational studies of Zika virus infection: A scoping review of research protocols

Azithromycin Inhibits the Replication of Zika Virus

Development of a Zika Virus Infection Model in Cynomolgus Macaques

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