scholarly journals The Race To Find Antivirals for Zika Virus

2017 ◽  
Vol 61 (6) ◽  
Author(s):  
Juan-Carlos Saiz ◽  
Miguel A. Martín-Acebes
Keyword(s):  
Antiviral Activity ◽  
Antiviral Therapy ◽  
Zika Virus ◽  
Neurological Disorders ◽  
Bioactive Molecules ◽  
Guillain Barre Syndrome ◽  
Great Effort ◽  
The Past ◽  
Viral Components ◽  
Specific Antiviral Therapy

ABSTRACT Zika virus (ZIKV), a flavivirus transmitted by mosquitoes, was an almost neglected pathogen until its introduction in the Americas in 2015 and its subsequent explosive spread throughout the continent, where it has infected millions of people. The virus has caused social and sanitary alarm, mainly due to its association with severe neurological disorders (Guillain-Barré syndrome and microcephaly in fetuses and newborns). Nowadays, no specific antiviral therapy against ZIKV is available. However, during the past months, a great effort has been made to search for antiviral candidates using different approaches and methodologies, ranging from testing specific compounds with known antiviral activity to the screening of libraries with hundreds of bioactive molecules. The identified antiviral candidates include drugs targeting viral components as well as cellular ones. Here, an updated review of what has been done in this line is presented.

scholarly journals Host-Directed Antivirals: a Realistic Alternative to Fight Zika Virus

2018 ◽  
Author(s):  
Juan-Carlos Saiz ◽  
Nereida Jiménez de Oya ◽  
Ana-Belén Blázquez ◽  
Estela Escribano-Romero ◽  
Miguel A. Martín-Acebes
Keyword(s):  
Global Health ◽  
Antiviral Activity ◽  
Zika Virus ◽  
Current Knowledge ◽  
Structural Proteins ◽  
Great Effort ◽  
Zikv Infection ◽  
Rapid Spread ◽  
Viral Components ◽  
Specific Antiviral Therapy

Zika virus (ZIKV), a mosquito-borne flavivirus, was an almost neglected pathogen until its introduction in the Americas in 2015, where it has been responsible for a threat to global health, causing a great social and sanitary alarm due to its increased virulence, rapid spread, and an association with severe neurological and ophthalmological complications. Currently, no specific antiviral therapy against ZIKV is available, and treatments are palliative and mainly directed to symptoms relief, such as fever and rash, by administering antipyretics, anti-histamines, and fluids for dehydration. Nevertheless, lately, a great effort has been made to search for antiviral candidates using different approaches and methodologies, ranging from repurposing of specific compounds with known antiviral activity to the screening of libraries and of natural compounds. The identified antiviral candidates include drugs targeting viral components (structural proteins and enzymes), as well as cellular ones. Here, we present an updated review of current knowledge about anti-ZIKV strategies, focusing on host-directed antivirals as a realistic alternative to combat ZIKV infection.

scholarly journals Zika Virus: The Agent and Its Biology, With Relevance to Pathology

2016 ◽  
Vol 141 (1) ◽  
pp. 33-42 ◽  
Author(s):  
Carey L. Medin ◽  
Alan L. Rothman
Keyword(s):  
Zika Virus ◽  
Structural Characteristics ◽  
Review Article ◽  
Western Hemisphere ◽  
Guillain Barre Syndrome ◽  
Congenital Infections ◽  
The Past ◽  
Recent Introduction ◽  
Guillain Barré ◽  
Scientific Attention

Once obscure, Zika virus (ZIKV) has attracted significant medical and scientific attention in the past year because of large outbreaks associated with the recent introduction of this virus into the Western hemisphere. In particular, the occurrence of severe congenital infections and cases of Guillain-Barré syndrome has placed this virus squarely in the eyes of clinical and anatomic pathologists. This review article provides a basic introduction to ZIKV, its genetics, its structural characteristics, and its biology. A multidisciplinary effort will be essential to establish clinicopathologic correlations of the basic virology of ZIKV in order to advance development of diagnostics, therapeutics, and vaccines.

scholarly journals Host-Directed Antivirals: A Realistic Alternative to Fight Zika Virus

Viruses ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 453 ◽  
Author(s):  
Juan-Carlos Saiz ◽  
Nereida Oya ◽  
Ana-Belén Blázquez ◽  
Estela Escribano-Romero ◽  
Miguel Martín-Acebes
Keyword(s):  
Global Health ◽  
Antiviral Activity ◽  
Zika Virus ◽  
Current Knowledge ◽  
Structural Proteins ◽  
Zikv Infection ◽  
Rapid Spread ◽  
Different Sources ◽  
Specific Antiviral Therapy ◽  
Do So

Zika virus (ZIKV), a mosquito-borne flavivirus, was an almost neglected pathogen until its introduction in the Americas in 2015, where it has been responsible for a threat to global health, causing a great social and sanitary alarm due to its increased virulence, rapid spread, and an association with severe neurological and ophthalmological complications. Currently, no specific antiviral therapy against ZIKV is available, and treatments are palliative and mainly directed toward the relief of symptoms, such as fever and rash, by administering antipyretics, anti-histamines, and fluids for dehydration. Nevertheless, lately, search for antivirals has been a major aim in ZIKV investigations. To do so, screening of libraries from different sources, testing of natural compounds, and repurposing of drugs with known antiviral activity have allowed the identification of several antiviral candidates directed to both viral (structural proteins and enzymes) and cellular elements. Here, we present an updated review of current knowledge about anti-ZIKV strategies, focusing on host-directed antivirals as a realistic alternative to combat ZIKV infection.

Neurological Disorders

2017 ◽  
Author(s):  
Margit L. Bleecker
Keyword(s):  
Carbon Monoxide ◽  
Neurological Disorders ◽  
Occupational Exposures ◽  
Signs And Symptoms ◽  
Dose Effect ◽  
Temporal Association ◽  
Biological Plausibility ◽  
Cognitive Domains ◽  
The Past ◽  
Neurologic Disorders

This chapter describes neurologic disorders related primarily to occupational exposures along with presenting signs and symptoms. Acute or subacute occupational exposure to high levels of neurotoxic compounds, which occurred in the past and resulted in unique presentations of neurological disorders, occur infrequently today. Sections include the evaluation of toxic neuropathies and the approach to neurobehavioral impairment along with the cognitive domains commonly affected with exposure to neurointoxicants. A section describes the approach to a patient with exposure to neurointoxicants that includes the need for a temporal association between exposure and effect, a dose-effect relationship, biological plausibility, and other causes eliminated Effects of selected neurotoxins are described, including carbon monoxide, lead, organic solvents, and manganese.

Antiviral activity of glycyrrhizic acid conjugates with amino acid esters against Zika virus

2021 ◽  
Vol 294 ◽  
pp. 198290
Author(s):  
Lidia A. Baltina ◽  
Mann-Jen Hour ◽  
Ya-Chi Liu ◽  
Young-Sheng Chang ◽  
Su-Hua Huang ◽  
...  
Keyword(s):  
Amino Acid ◽  
Antiviral Activity ◽  
Zika Virus ◽  
Glycyrrhizic Acid ◽  
Amino Acid Esters ◽  
Acid Esters

scholarly journals Topical Astodrimer Sodium, a Non-Toxic Polyanionic Dendrimer, Demonstrates Antiviral Activity in an Experimental Ocular Adenovirus Infection Model

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3419
Author(s):  
Eric G. Romanowski ◽  
Kathleen A. Yates ◽  
Jeremy R. A. Paull ◽  
Graham P. Heery ◽  
Robert M. Q. Shanks
Keyword(s):  
Antiviral Activity ◽  
Antiviral Therapy ◽  
Infection Model ◽  
Adenovirus Infection ◽  
Antiviral Efficacy ◽  
Ocular Infections ◽  
Further Development ◽  
Ocular Tolerability ◽  
Efficacy Studies ◽  
Viral Titers

There is no approved antiviral therapy for adenovirus (HAdV) ocular infections. Astodrimer sodium (SPL7013) is a polyanionic dendrimer with antiviral activity. The current study evaluated the ocular tolerability and anti-adenoviral efficacy of topical SPL7013 in rabbit ocular models. In a tolerability study, rabbits were treated with 3% SPL7013, vehicle, or 0.5% cidofovir. Their eyes were graded using the Draize scale. In antiviral efficacy studies, HAdV5 inoculated eyes were treated with 3% SPL7013, vehicle, or 0.5% cidofovir. Eyes were cultured for the virus on days 0, 1, 3, 4, 5, 7, 9, 11, and 14. Viral titers were determined. There were no differences in Draize scores between 3% SPL7013 and vehicle on any day. Cidofovir produced significantly higher Draize scores on day 12 than SPL7013 and vehicle. The 3% SPL7013 and 0.5% cidofovir significantly reduced daily viral titers and positive cultures per total compared with vehicle on several different days. The 3% SPL7013 and 0.5% cidofovir significantly reduced the duration of HAdV5 shedding compared to vehicle. The 3% SPL7013 demonstrated significantly more antiviral activity compared with vehicle in the Ad5/NZW rabbit ocular model. The 3% SPL7013 induced “minimal” to “practically non-irritating” Draize scores in the ocular tolerability study. Further development of astodrimer sodium as a topical antiviral therapy for adenoviral ocular infections is indicated.

scholarly journals 4,7-Disubstituted 7H-Pyrrolo[2,3-d]pyrimidines and Their Analogs as Antiviral Agents against Zika Virus

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3779
Author(s):  
Ruben Soto-Acosta ◽  
Eunkyung Jung ◽  
Li Qiu ◽  
Daniel J. Wilson ◽  
Robert J. Geraghty ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Dengue Virus ◽  
Small Molecules ◽  
Zika Virus ◽  
Antiviral Agents ◽  
Structural Features ◽  
Molecular Target ◽  
Core Structure ◽  
Human Pathogens ◽  
Important Group

Discovery of compound 1 as a Zika virus (ZIKV) inhibitor has prompted us to investigate its 7H-pyrrolo[2,3-d]pyrimidine scaffold, revealing structural features that elicit antiviral activity. Furthermore, we have demonstrated that 9H-purine or 1H-pyrazolo[3,4-d]pyrimidine can serve as an alternative core structure. Overall, we have identified 4,7-disubstituted 7H-pyrrolo[2,3-d]pyrimidines and their analogs including compounds 1, 8 and 11 as promising antiviral agents against flaviviruses ZIKV and dengue virus (DENV). While the molecular target of these compounds is yet to be elucidated, 4,7-disubstituted 7H-pyrrolo[2,3-d]pyrimidines and their analogs are new chemotypes in the design of small molecules against flaviviruses, an important group of human pathogens.

scholarly journals The Clinical Utility of Virtual Reality in Neurorehabilitation: A Systematic Review

2018 ◽  
Vol 10 ◽  
pp. 117957351881354 ◽  
Author(s):  
Thais Massetti ◽  
Talita Dias da Silva ◽  
Tânia Brusque Crocetta ◽  
Regiani Guarnieri ◽  
Bruna Leal de Freitas ◽  
...  
Keyword(s):  
Systematic Review ◽  
Virtual Reality ◽  
Virtual Environments ◽  
Neurological Disorders ◽  
Clinical Utility ◽  
Spinal Cord Injuries ◽  
Web Of Science ◽  
The Past ◽  
Meta Analyses ◽  
The Impact

Background: Virtual reality (VR) experiences (through games and virtual environments) are increasingly being used in physical, cognitive, and psychological interventions. However, the impact of VR as an approach to rehabilitation is not fully understood, and its advantages over traditional rehabilitation techniques are yet to be established. Method: We present a systematic review which was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). During February and March of 2018, we conducted searches on PubMed (Medline), Virtual Health Library Search Portal databases (BVS), Web of Science (WOS), and Embase for all VR-related publications in the past 4 years (2015, 2016, 2017, and 2018). The keywords used in the search were “neurorehabilitation” AND “Virtual Reality” AND “devices.” Results: We summarize the literature which highlights that a range of effective VR approaches are available. Studies identified were conducted with poststroke patients, patients with cerebral palsy, spinal cord injuries, and other pathologies. Healthy populations have been used in the development and testing of VR approaches meant to be used in the future by people with neurological disorders. A range of benefits were associated with VR interventions, including improvement in motor functions, greater community participation, and improved psychological and cognitive function. Conclusions: The results from this review provide support for the use of VR as part of a neurorehabilitation program in maximizing recovery.

scholarly journals Subversion of the Heme Oxygenase-1 Antiviral Activity by Zika Virus

Viruses ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 2 ◽  
Author(s):  
Chaker El Kalamouni ◽  
Etienne Frumence ◽  
Sandra Bos ◽  
Jonathan Turpin ◽  
Brice Nativel ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Heme Oxygenase ◽  
Zika Virus ◽  
Fluorescent Protein ◽  
Human Cells ◽  
Heme Oxygenase 1 ◽  
Viral Inhibition ◽  
Reporter Protein ◽  
Wide Range ◽  
Rna Replicon

Heme oxygenase-1 (HO-1), a rate-limiting enzyme involved in the degradation of heme, is induced in response to a wide range of stress conditions. HO-1 exerts antiviral activity against a broad range of viruses, including the Hepatitis C virus, the human immunodeficiency virus, and the dengue virus by inhibiting viral growth. It has been reported that HO-1 displays antiviral activity against the Zika virus (ZIKV) but the mechanisms of viral inhibition remain largely unknown. Using a ZIKV RNA replicon with the Green Fluorescent Protein (GFP) as a reporter protein, we were able to show that HO-1 expression resulted in the inhibition of viral RNA replication. Conversely, we observed a decrease in HO-1 expression in cells replicating the ZIKV RNA replicon. The study of human cells infected with ZIKV showed that the HO-1 expression level was significantly lower once viral replication was established, thereby limiting the antiviral effect of HO-1. Our work highlights the capacity of ZIKV to thwart the anti-replicative activity of HO-1 in human cells. Therefore, the modulation of HO-1 as a novel therapeutic strategy against ZIKV infection may display limited effect.

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