Zika Virus: Therapeutic Advances

A special issue of Pharmaceuticals (ISSN 1424-8247).

Deadline for manuscript submissions: closed (30 April 2020) | Viewed by 30585

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Guest Editor
Department of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Madrid, Spain
Interests: flavivirus; Coronavirus; zoonosis; virus-host interactions; antivirals; vaccines
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Dear Colleagues,

When the Zika virus (ZIKV) was first discovered in Africa in 1947, it was considered responsible for an almost negligible disease, since its infection was usually asymptomatic or produced a relatively mild illness followed by an uneventful recovery. However, after its spread in Asia in the 1980s, its subsequent outbreaks in Micronesia and French Polynesia in this century, and its recent introduction in the Americas, ZIKV now constitutes a threat to global health, causing a great social and sanitary alarm due to its association with severe neurological and ophthalmological complications. Currently, no specific vaccines or antiviral therapies against ZIKV are available, and treatments are palliative and mainly directed to symptoms relief. Nevertheless, a great effort has been made lately to search for efficient therapeutic tools (antivirals and vaccines) and to understand the involved molecular mechanisms. 

To achieve a more comprehensive understanding of the current trends in the development of new therapeutic approaches, the journal Pharmaceuticals now invites valuable contributions that report original observations or reviews on this matter.

Dr. Juan-Carlos Saiz
Guest Editor

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Keywords

  • Zika virus
  • virus-host cell interactions
  • therapeutic
  • antivirals
  • vaccines

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Published Papers (5 papers)

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Review

36 pages, 2550 KiB  
Review
Computer-Assisted and Data Driven Approaches for Surveillance, Drug Discovery, and Vaccine Design for the Zika Virus
by Subhash C. Basak, Subhabrata Majumdar, Ashesh Nandy, Proyasha Roy, Tathagata Dutta, Marjan Vracko and Apurba K. Bhattacharjee
Pharmaceuticals 2019, 12(4), 157; https://doi.org/10.3390/ph12040157 - 16 Oct 2019
Cited by 13 | Viewed by 5017
Abstract
Human life has been at the edge of catastrophe for millennia due diseases which emerge and reemerge at random. The recent outbreak of the Zika virus (ZIKV) is one such menace that shook the global public health community abruptly. Modern technologies, including computational [...] Read more.
Human life has been at the edge of catastrophe for millennia due diseases which emerge and reemerge at random. The recent outbreak of the Zika virus (ZIKV) is one such menace that shook the global public health community abruptly. Modern technologies, including computational tools as well as experimental approaches, need to be harnessed fast and effectively in a coordinated manner in order to properly address such challenges. In this paper, based on our earlier research, we have proposed a four-pronged approach to tackle the emerging pathogens like ZIKV: (a) Epidemiological modelling of spread mechanisms of ZIKV; (b) assessment of the public health risk of newly emerging strains of the pathogens by comparing them with existing strains/pathogens using fast computational sequence comparison methods; (c) implementation of vaccine design methods in order to produce a set of probable peptide vaccine candidates for quick synthesis/production and testing in the laboratory; and (d) designing of novel therapeutic molecules and their laboratory testing as well as validation of new drugs or repurposing of drugs for use against ZIKV. For each of these stages, we provide an extensive review of the technical challenges and current state-of-the-art. Further, we outline the future areas of research and discuss how they can work together to proactively combat ZIKV or future emerging pathogens. Full article
(This article belongs to the Special Issue Zika Virus: Therapeutic Advances)
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29 pages, 458 KiB  
Review
Therapeutic Advances Against ZIKV: A Quick Response, a Long Way to Go
by Juan-Carlos Saiz
Pharmaceuticals 2019, 12(3), 127; https://doi.org/10.3390/ph12030127 - 30 Aug 2019
Cited by 12 | Viewed by 4643
Abstract
Zika virus (ZIKV) is a mosquito-borne flavivirus that spread throughout the American continent in 2015 causing considerable worldwide social and health alarm due to its association with ocular lesions and microcephaly in newborns, and Guillain–Barré syndrome (GBS) cases in adults. Nowadays, no licensed [...] Read more.
Zika virus (ZIKV) is a mosquito-borne flavivirus that spread throughout the American continent in 2015 causing considerable worldwide social and health alarm due to its association with ocular lesions and microcephaly in newborns, and Guillain–Barré syndrome (GBS) cases in adults. Nowadays, no licensed vaccines or antivirals are available against ZIKV, and thus, in this very short time, the scientific community has conducted enormous efforts to develop vaccines and antivirals. So that, different platforms (purified inactivated and live attenuated viruses, DNA and RNA nucleic acid based candidates, virus-like particles, subunit elements, and recombinant viruses) have been evaluated as vaccine candidates. Overall, these vaccines have shown the induction of vigorous humoral and cellular responses, the decrease of viremia and viral RNA levels in natural target organs, the prevention of vertical and sexual transmission, as well as that of ZIKV-associated malformations, and the protection of experimental animal models. Some of these vaccine candidates have already been assayed in clinical trials. Likewise, the search for antivirals have also been the focus of recent investigations, with dozens of compounds tested in cell culture and a few in animal models. Both direct acting antivirals (DAAs), directed to viral structural proteins and enzymes, and host acting antivirals (HAAs), directed to cellular factors affecting all steps of the viral life cycle (binding, entry, fusion, transcription, translation, replication, maturation, and egress), have been evaluated. It is expected that this huge collaborative effort will produce affordable and effective therapeutic and prophylactic tools to combat ZIKV and other related still unknown or nowadays neglected flaviviruses. Here, a comprehensive overview of the advances made in the development of therapeutic measures against ZIKV and the questions that still have to be faced are summarized. Full article
(This article belongs to the Special Issue Zika Virus: Therapeutic Advances)
15 pages, 888 KiB  
Review
Antiviral Agents in Development for Zika Virus Infections
by Mariana Baz and Guy Boivin
Pharmaceuticals 2019, 12(3), 101; https://doi.org/10.3390/ph12030101 - 29 Jun 2019
Cited by 50 | Viewed by 8405
Abstract
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. [...] Read more.
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. Full article
(This article belongs to the Special Issue Zika Virus: Therapeutic Advances)
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11 pages, 497 KiB  
Review
Lipid Metabolism as a Source of Druggable Targets for Antiviral Discovery against Zika and Other Flaviviruses
by Miguel A. Martín-Acebes, Nereida Jiménez de Oya and Juan-Carlos Saiz
Pharmaceuticals 2019, 12(2), 97; https://doi.org/10.3390/ph12020097 - 21 Jun 2019
Cited by 36 | Viewed by 6010
Abstract
The Zika virus (ZIKV) is a mosquito-borne flavivirus that can lead to birth defects (microcephaly), ocular lesions and neurological disorders (Guillain-Barré syndrome). There is no licensed vaccine or antiviral treatment against ZIKV infection. The effort to understand the complex interactions of ZIKV with [...] Read more.
The Zika virus (ZIKV) is a mosquito-borne flavivirus that can lead to birth defects (microcephaly), ocular lesions and neurological disorders (Guillain-Barré syndrome). There is no licensed vaccine or antiviral treatment against ZIKV infection. The effort to understand the complex interactions of ZIKV with cellular networks contributes to the identification of novel host-directed antiviral (HDA) candidates. Among the cellular pathways involved in infection, lipid metabolism gains attention. In ZIKV-infected cells lipid metabolism attributed to intracellular membrane remodeling, virion morphogenesis, autophagy modulation, innate immunity and inflammation. The key roles played by the cellular structures associated with lipid metabolism, such as peroxisomes and lipid droplets, are starting to be deciphered. Consequently, there is a wide variety of lipid-related antiviral strategies that are currently under consideration, which include an inhibition of sterol regulatory element-binding proteins (SREBP), the activation of adenosine-monophosphate activated kinase (AMPK), an inhibition of acetyl-Coenzyme A carboxylase (ACC), interference with sphingolipid metabolism, blockage of intracellular cholesterol trafficking, or a treatment with cholesterol derivatives. Remarkably, most of the HDAs identified in these studies are also effective against flaviviruses other than ZIKV (West Nile virus and dengue virus), supporting their broad-spectrum effect. Considering that lipid metabolism is one of the main cellular pathways suitable for pharmacological intervention, the idea of repositioning drugs targeting lipid metabolism as antiviral candidates is gaining force. Full article
(This article belongs to the Special Issue Zika Virus: Therapeutic Advances)
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21 pages, 654 KiB  
Review
Late Neurological Consequences of Zika Virus Infection: Risk Factors and Pharmaceutical Approaches
by Isis N. O. Souza, Fernanda G. Q. Barros-Aragão, Paula S. Frost, Claudia P. Figueiredo and Julia R. Clarke
Pharmaceuticals 2019, 12(2), 60; https://doi.org/10.3390/ph12020060 - 17 Apr 2019
Cited by 20 | Viewed by 5853
Abstract
Zika virus (ZIKV) infection was historically considered a disease with mild symptoms and no major consequences to human health. However, several long-term, late onset, and chronic neurological complications, both in congenitally-exposed babies and in adult patients, have been reported after ZIKV infection, especially [...] Read more.
Zika virus (ZIKV) infection was historically considered a disease with mild symptoms and no major consequences to human health. However, several long-term, late onset, and chronic neurological complications, both in congenitally-exposed babies and in adult patients, have been reported after ZIKV infection, especially after the 2015 epidemics in the American continent. The development or severity of these conditions cannot be fully predicted, but it is possible that genetic, epigenetic, and environmental factors may contribute to determine ZIKV infection outcomes. This reinforces the importance that individuals exposed to ZIKV are submitted to long-term clinical surveillance and highlights the urgent need for the development of therapeutic approaches to reduce or eliminate the neurological burden of infection. Here, we review the epidemiology of ZIKV-associated neurological complications and the role of factors that may influence disease outcome. Moreover, we discuss experimental and clinical evidence of drugs that have shown promising results in vitro or in vitro against viral replication and and/or ZIKV-induced neurotoxicity. Full article
(This article belongs to the Special Issue Zika Virus: Therapeutic Advances)
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