scholarly journals Antiviral Agents in Development for Zika Virus Infections

2019 ◽  
Vol 12 (3) ◽  
pp. 101 ◽  
Author(s):  
Baz ◽  
Boivin

In 1947, Zika virus (ZIKV), a mosquito-borne flavivirus was identified in Uganda and subsequently spread to Asia and the Pacific regions. In 2015, it was introduced in Brazil causing an important social and sanitary alarm due to its increased virulence and rapid dissemination. Importantly, ZIKV infections have been associated with severe neurological complications such as Guillain–Barré syndrome and microcephaly in fetuses and newborns. Although enormous efforts were made by investigators in the development of effective countermeasures against ZIKV, there is still no approved specific antiviral drug for the treatment of ZIKV infections. Herein, we review several anti ZIKV candidates including drugs targeting both the virus (structural proteins and enzymes) and cellular elements.

2016 ◽  
Author(s):  
Adam J. Kucharski ◽  
Sebastian Funk ◽  
Rosalind M. Eggo ◽  
Henri-Pierre Mallet ◽  
W. John Edmunds ◽  
...  

AbstractBetween October 2013 and April 2014, more than 30,000 cases of Zika virus (ZIKV) disease were estimated to have attended healthcare facilities in French Polynesia. ZIKV has also been reported in Africa and Asia, and in 2015 the virus spread to South America and the Caribbean. Infection with ZIKV has been associated with neurological complications including Guillain-Barré Syndrome (GBS) and microcephaly, which led the World Health Organization to declare a Public Health Emergency of International Concern in February 2015. To better understand the transmission dynamics of ZIKV, we used a mathematical model to examine the 2013–14 outbreak on the six major archipelagos of French Polynesia. Our median estimates for the basic reproduction number ranged from 2.6–4.8, with an estimated 11.5% (95% CI: 7.32–17.9%) of total infections reported. As a result, we estimated that 94% (95% CI: 91–97%) of the total population of the six archipelagos were infected during the outbreak. Based on the demography of French Polynesia, our results imply that if ZIKV infection provides complete protection against future infection, it would take 12–20 years before there are a sufficient number of susceptible individuals for ZIKV to reemerge, which is on the same timescale as the circulation of dengue virus serotypes in the region. Our analysis suggests that ZIKV may exhibit similar dynamics to dengue virus in island populations, with transmission characterized by large, sporadic outbreaks with a high proportion of asymptomatic or unreported cases.Author SummarySince the first reported major outbreak of Zika virus disease in Micronesia in 2007, the virus has caused outbreaks throughout the Pacific and South America. Transmitted by the Aedes species of mosquitoes, the virus has been linked to possible neurological complications including Guillain-Barre Syndrome and microcephaly. To improve our understanding of the transmission dynamics of Zika virus in island populations, we analysed the 2013–14 outbreak on the six major archipelagos of French Polynesia. We found evidence that Zika virus infected the majority of population, but only around 12% of total infections on the archipelagos were reported as cases. If infection with Zika virus generates lifelong immunity, we estimate that it would take at least 15–20 years before there are enough susceptible people for the virus to reemerge. Our results suggest that Zika virus could exhibit similar dynamics to dengue virus in the Pacific, producing large but sporadic outbreaks in small island populations.


2016 ◽  
Vol 74 (3) ◽  
pp. 253-255 ◽  
Author(s):  
Lucas Masiêro Araujo ◽  
Maria Lucia Brito Ferreira ◽  
Osvaldo JM Nascimento

ABSTRACT Zika virus (ZIKV) is now considered an emerging flavivirosis, with a first large outbreak registered in the Yap Islands in 2007. In 2013, a new outbreak was reported in the French Polynesia, with associated cases of neurological complications including Guillain-Barré syndrome (GBS). The incidence of GBS has increased in Brazil since 2015, what is speculated to be secondary to the ZIKV infection outbreak. The gold-standard test for detection of acute ZIKV infection is the polymerase-chain reaction technique, an essay largely unavailable in Brazil. The diagnosis of GBS is feasible even in resource-limited areas using the criteria proposed by the GBS Classification Group, which is based solely on clinical grounds. Further understanding on the relationship of ZIKV with neurological complications is a research urgency.


2019 ◽  
Vol 93 (16) ◽  
Author(s):  
Anna Dukhovny ◽  
Kevin Lamkiewicz ◽  
Qian Chen ◽  
Markus Fricke ◽  
Nabila Jabrane-Ferrat ◽  
...  

ABSTRACT Zika virus (ZIKV) is an arthropod-borne emerging pathogen causing febrile illness. ZIKV is associated Guillain-Barré syndrome and other neurological complications. Infection during pregnancy is associated with pregnancy complications and developmental and neurological abnormalities collectively defined as congenital Zika syndrome. There is still no vaccine or specific treatment for ZIKV infection. To identify host factors that can rescue cells from ZIKV infection, we used a genome-scale CRISPR activation screen. Our highly ranking hits included a short list of interferon-stimulated genes (ISGs) previously reported to have antiviral activity. Validation of the screen results highlighted interferon lambda 2 (IFN-λ2) and interferon alpha-inducible protein 6 (IFI6) as genes providing high levels of protection from ZIKV. Activation of these genes had an effect on an early stage in viral infection. In addition, infected cells expressing single guide RNAs (sgRNAs) for both of these genes displayed lower levels of cell death than did the controls. Furthermore, the identified genes were significantly induced in ZIKV-infected placenta explants. Thus, these results highlight a set of ISGs directly relevant for rescuing cells from ZIKV infection or its associated cell death and substantiate CRISPR activation screens as a tool to identify host factors impeding pathogen infection. IMPORTANCE Zika virus (ZIKV) is an emerging vector-borne pathogen causing a febrile disease. ZIKV infection might also trigger Guillain-Barré syndrome, neuropathy, and myelitis. Vertical transmission of ZIKV can cause fetus demise, stillbirth, or severe congenital abnormalities and neurological complications. There is no vaccine or specific antiviral treatment against ZIKV. We used a genome-wide CRISPR activation screen, where genes are activated from their native promoters to identify host cell factors that protect cells from ZIKV infection or associated cell death. The results provide a better understanding of key host factors that protect cells from ZIKV infection and might assist in identifying novel antiviral targets.


2019 ◽  
Vol 15 (2) ◽  
pp. 166-171
Author(s):  
Jose Marchan

After the outbreak in French Polynesia, Zika virus (ZIKV) explosive pandemic occurred in 2015, reports that ZIKV was linked to other diseases, especially neurological complications such as Guillain-Barré Syndrome (GBS), also burst in almost every continent, thereby turning into an international concern. In South America, the highest incidence occurred in Venezuela with approximately 680 cases of GBS after ZIKV infection. Currently, the main roots of this association remain unknown. In this regard, it is thought that the immune system plays a central role in such association through the host protection or even improving ZIKV establishment and progression. Nonneutralizing auto-antibodies, the complement system, self-reactive T cells, inflammation, the “cytokine storm”, prior exposures to other arboviruses such as dengue virus and chikungunya virus, the age and genetic susceptibility of the patient, and the biology of the vector are the main determinant factors, which perhaps, are involved in the pathological relationship: ZIKV and GBS. On the other hand, more multidisciplinary studies are required to provide means to develop effective therapeutics against this new global health threat that represents an emerging danger that can increase again and trigger other neurological disorders.


2016 ◽  
Vol 375 (16) ◽  
pp. 1598-1601 ◽  
Author(s):  
Thais dos Santos ◽  
Angel Rodriguez ◽  
Maria Almiron ◽  
Antonio Sanhueza ◽  
Pilar Ramon ◽  
...  

PLoS Medicine ◽  
2017 ◽  
Vol 14 (1) ◽  
pp. e1002203 ◽  
Author(s):  
Fabienne Krauer ◽  
Maurane Riesen ◽  
Ludovic Reveiz ◽  
Olufemi T. Oladapo ◽  
Ruth Martínez-Vega ◽  
...  

2020 ◽  
Vol 27 (7) ◽  
Author(s):  
Kevan M Akrami ◽  
Betania Mara Freitas de Nogueira ◽  
Mateus Santana do Rosário ◽  
Laise de Moraes ◽  
Marli Tenório Cordeiro ◽  
...  

Zika virus cases in Brazil have diminished since emergence in 2015. We report Guillain Barré Syndrome caused by Zika and possible Chikungunya co-infection during an expected low arboviral season. This case highlights the importance of clinical vigilance for Zika in those with neurological syndromes outside typical arboviral season.


F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 196 ◽  
Author(s):  
Michel Jacques Counotte ◽  
Dianne Egli-Gany ◽  
Maurane Riesen ◽  
Million Abraha ◽  
Teegwendé Valérie Porgo ◽  
...  

Background. The Zika virus (ZIKV) outbreak in the Americas has caused international concern due to neurological sequelae linked to the infection, such as microcephaly and Guillain-Barré syndrome (GBS). The World Health Organization stated that there is “sufficient evidence to conclude that Zika virus is a cause of congenital abnormalities and is a trigger of GBS”. This conclusion was based on a systematic review of the evidence published until 30.05.2016. Since then, the body of evidence has grown substantially, leading to this update of that systematic review with new evidence published from 30.05.2016 – 18.01.2017, update 1. Methods. We review evidence on the causal link between ZIKV infection and adverse congenital outcomes and the causal link between ZIKV infection and GBS or immune-mediated thrombocytopaenia purpura. We also describe the transition of the review into a living systematic review, a review that is continually updated. Results. Between 30.05.2016 and 18.01.2017, we identified 2413 publications, of which 101 publications were included. The evidence added in this update confirms the conclusion of a causal association between ZIKV and adverse congenital outcomes. New findings expand the evidence base in the dimensions of biological plausibility, strength of association, animal experiments and specificity. For GBS, the body of evidence has grown during the search period for update 1, but only for dimensions that were already populated in the previous version. There is still a limited understanding of the biological pathways that potentially cause the occurrence of autoimmune disease following ZIKV infection. Conclusions. This systematic review confirms previous conclusions that ZIKV is a cause of congenital abnormalities, including microcephaly, and is a trigger of GBS. The transition to living systematic review techniques and methodology provides a proof of concept for the use of these methods to synthesise evidence about an emerging pathogen such as ZIKV.


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