Flavivirus ; Humans ; Immunity ; Vaccines ; Zika Virus ; Zika Virus Infection/prevention & control*

Viral infection is clinically common and some viral diseases, such as the ongoing global outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), have high morbidity and mortality. However, most viral infections are currently lacking in specific therapeutic agents and effective prophylactic vaccines, due to inadequate response, increased rate of drug resistance and severe adverse side effects. Therefore, it is urgent to find new specific therapeutic targets for antiviral defense among which "peptide-based therapeutics" is an emerging field. Peptides may be promising antiviral drugs because of their high efficacy and low toxic side effects. Vasoactive intestinal peptide (VIP) is a prospective antiviral peptide. Since its successful isolation in 1970, VIP has been reported to be involved in infections of SARS-CoV-2, human immune deficiency virus (HIV), vesicular stomatitis virus (VSV), respiratory syncytial virus (RSV), Zika virus (ZIKV) and cytomegalovirus (CMV). Additionally, given that viral attacks sometimes cause severe complications due to overaction of inflammatory and immune responses, the potent anti-inflammatory and immunoregulator properties of VIP facilitate it to be a powerful and promising candidate. This review summarizes the role and mechanisms of VIP in all reported viral infections and suggests its clinical potential as an antiviral therapeutic target.
Antiviral Agents/therapeutic use* ; COVID-19/drug therapy* ; Humans ; Prospective Studies ; SARS-CoV-2 ; Vasoactive Intestinal Peptide/therapeutic use* ; Zika Virus ; Zika Virus Infection/drug therapy*

Zika virus (ZIKV) is an emerging pathogen associated with neurological complications, such as Guillain-Barré syndrome in adults and microcephaly in fetuses and newborns. This mosquito-borne flavivirus causes important social and sanitary problems owing to its rapid dissemination. However, the development of antivirals against ZIKV is lagging. Although various strategies have been used to study anti-ZIKV agents, approved drugs or vaccines for the treatment (or prevention) of ZIKV infections are currently unavailable. Repurposing clinically approved drugs could be an effective approach to quickly respond to an emergency outbreak of ZIKV infections. The well-established safety profiles and optimal dosage of these clinically approved drugs could provide an economical, safe, and efficacious approach to address ZIKV infections. This review focuses on the recent research and development of agents against ZIKV infection by repurposing clinical drugs. Their characteristics, targets, and potential use in anti-ZIKV therapy are presented. This review provides an update and some successful strategies in the search for anti-ZIKV agents are given.
Adult ; Animals ; Drug Repositioning ; Humans ; Infant, Newborn ; Microcephaly ; Pharmaceutical Preparations ; Zika Virus ; Zika Virus Infection/prevention & control*

OBJECTIVE: To establish a non-coated enzyme-linked immunosorbent assay (ELISA) based on zika virus envelope (E) protein for detecting the expression of E protein in infected cells. METHODS: Adherent Vero-143 cells infected with zika virus in a 96-well plate were fixed, and the antibodies against zika virus E protein were added at an optimized concentration to establish the non-coated ELISA method for E protein. The antiviral activities of lignans compound C1 was evaluated using this method. The accuracy of this non-coated ELISA was verified by RT-PCR, and the cross reaction with dengue virus was assessed. RESULTS: After optimization, the background absorbance at 450 nm of uninfected cells was reduced to about 0.20. The antiviral activities of lignans compound C1 detected by this method were basically consistent with the results of RT-PCR. No cross reaction with dengue virus was found in this assay. CONCLUSIONS A non- coated ELISA method based on zika virus E protein was established, which can be used for screening antiviral agents against zika virus.
Antibodies, Viral ; Enzyme-Linked Immunosorbent Assay ; Humans ; Immunoglobulin G ; Immunoglobulin M ; Viral Envelope Proteins ; Zika Virus ; Zika Virus Infection

OBJECTIVES: Dengue epidemic is a dynamic and complex phenomenon that has gained considerable attention due to its injurious effects. The focus of this study is to statically analyze the nature of the dengue epidemic network in terms of whether it follows the features of a scale-free network or a random network. METHODS: A multifarious network of Aedes aegypti is addressed keeping the viewpoint of a complex system and modelled as a network. The dengue network has been transformed into a one-mode network from a two-mode network by utilizing projection methods. Furthermore, three network features have been analyzed, the power-law, clustering coefficient, and network visualization. In addition, five methods have been applied to calculate the global clustering coefficient. RESULTS: It has been observed that dengue epidemic follows a power-law, with the value of its exponent γ = −2.1. The value of the clustering coefficient is high for dengue cases, as weight of links. The minimum method showed the highest value among the methods used to calculate the coefficient. Network visualization showed the main areas. Moreover, the dengue situation did not remain the same throughout the observed period. CONCLUSIONS: The results showed that the network topology exhibits the features of a scale-free network instead of a random network. Focal hubs are highlighted and the critical period is found. Outcomes are important for the researchers, health officials, and policy makers who deal with arbovirus epidemic diseases. Zika virus and Chikungunya virus can also be modelled and analyzed in this manner.
Administrative Personnel ; Aedes ; Arboviruses ; Chikungunya virus ; Critical Period (Psychology) ; Dengue Virus ; Dengue ; Humans ; Methods ; Zika Virus

Zika virus (ZIKV) is one of the pathogens which is transmitted world widely, but there are no effective drugs and vaccines. Whole genome sequencing (WGS) of viruses could be applied to viral pathogen characterization, diagnosis, molecular surveillance, and even finding novel pathogens. We established an improved method using direct RNA sequencing with Nanopore technology to obtain WGS of ZIKV, after adding poly (A) tails to viral RNA. This established method does not require specific primers, complimentary DNA (cDNA) synthesis, and polymerase chain reaction (PCR)-based enrichment, resulting in the reduction of biases as well as of the ability to find novel RNA viruses. Nanopore technology also allows to read long sequences. It makes WGS easier and faster with long-read assembly. In this study, we obtained WGS of two strains of ZIKV following the established protocol. The sequenced reads resulted in 99% and 100% genome coverage with 63.5X and 21,136X, for the ZIKV PRVABC59 and MR 766 strains, respectively. The sequence identities of the ZIKV PRVABC59 and MR 766 strains for each reference genomes were 98.76% and 99.72%, respectively. We also found that the maximum length of reads was 10,311 bp which is almost the whole genome size of ZIKV. These long-reads could make overall structure of whole genome easily, and WGS faster and easier. The protocol in this study could provide rapid and efficient WGS that could be applied to study the biology of RNA viruses including identification, characterization, and global surveillance.
Bias (Epidemiology) ; Biology ; Diagnosis ; DNA ; Genome ; Genome Size ; Methods ; Nanopores ; Polymerase Chain Reaction ; RNA Viruses ; RNA ; RNA, Viral ; Sequence Analysis, RNA ; Tail ; Vaccines ; Zika Virus

Zika virus (ZIKV) is a mosquito-borne flavivirus associated with severe neurological disorders including Guillain-Barré syndrome and microcephaly. The host innate immune responses against ZIKV infection are essential for protection; however, ZIKV has evolved strategies to evade and antagonize antiviral responses via its nonstructural (NS) proteins. Here, we demonstrated that ZIKV infection unexpectedly inhibits NLRP3-dependent inflammasome activation in bone marrow-derived macrophages and mixed glial cells from mouse brain. ZIKV infection led to increased transcript levels of proinflammatory cytokines such as IL-1β and IL-6 via activating NF-κB signaling. However, ZIKV infection failed to trigger the secretion of active caspase-1 and IL-1β from macrophages and glial cells even in the presence of LPS priming or ATP costimulation. Intriguingly, ZIKV infection significantly attenuated NLRP3-dependent, but not absent in melanoma 2-dependent caspase-1 activation and IL-1β secretion from both cells. ZIKV infection further blocked apoptosis-associated speck-like protein containing a caspase recruitment domain oligomerization in LPS/ATP-stimulated macrophages. Interestingly, expression of ZIKV NS3 protein reduced NLRP3-mediated caspase-1 activation and IL-1β secretion in macrophages, whereas NS1 and NS5 proteins showed no effects. Furthermore, NLRP3 was found to be degraded by the overexpression of ZIKV NS3 in 293T cells. Collectively, these results indicate that ZIKV evades host NLRP3 inflammasome-mediated innate immune responses in macrophages and glial cells; this may facilitate ZIKV's ability to enhance the replication and dissemination in these cells.
Adenosine Triphosphate ; Animals ; Brain ; Caspase 1 ; Cytokines ; Flavivirus ; Guillain-Barre Syndrome ; HEK293 Cells ; Immunity, Innate ; Inflammasomes ; Interleukin-6 ; Macrophages ; Melanoma ; Mice ; Microcephaly ; Nervous System Diseases ; Neuroglia ; Zika Virus

OBJECTIVES: To estimate the number and risk of imported infections resulting from people visiting Asian and Latin American countries.METHODS: The dataset of visitors to 5 Asian countries with dengue were analyzed for 2016 and 2017, and in the Philippines, Thailand and Vietnam, imported cases of zika virus infection were also reported. For zika virus, a single imported case was reported from Brazil in 2016, and 2 imported cases reported from the Maldives in 2017. To understand the transmissibility in 5 Southeast Asian countries, the estimate of the force of infection, i.e., the hazard of infection per year and the average duration of travel has been extracted. Outbound travel numbers were retrieved from the World Tourism Organization, including business travelers.RESULTS: The incidence of imported dengue in 2016 was estimated at 7.46, 15.00, 2.14, 4.73 and 2.40 per 100,000 travelers visiting Philippines, Indonesia, Thailand, Malaysia and Vietnam, respectively. Similarly, 2.55, 1.65, 1.53, 1.86 and 1.70 per 100,000 travelers in 2017, respectively. It was estimated that there were 60.1 infections (range: from 16.8 to 150.7 infections) with zika virus in Brazil, 2016, and 345.6 infections (range: from 85.4 to 425.5 infections) with zika virus in the Maldives, 2017.CONCLUSION: This study emphasizes that dengue and zika virus infections are mild in their nature, and a substantial number of infections may go undetected. An appropriate risk assessment of zika virus infection must use the estimated total size of infections.
Asia, Southeastern ; Asian Continental Ancestry Group ; Brazil ; Commerce ; Dataset ; Dengue ; Humans ; Incidence ; Indian Ocean Islands ; Indonesia ; Korea ; Latin America ; Malaysia ; Philippines ; Risk Assessment ; Thailand ; Vietnam ; Zika Virus ; Zika Virus Infection

We developed a Rapid Diagnostic Test (RDT) kit for detecting IgG/IgM antibodies against Zika virus (ZIKV) using monoclonal antibodies to the envelope (E) and non-structural protein 1 (NS1) of ZIKV. These proteins were produced using baculovirus expression vector with Sf9 cells. Monoclonal antibodies J2G7 to NS1 and J5E1 to E protein were selected and conjugated with colloidal gold to produce the Zika IgG/IgM RDT kit (Zika RDT). Comparisons with ELISA, plaque reduction neutralization test (PRNT), and PCR were done to investigate the analytical sensitivity of Zika RDT, which resulted in 100% identical results. Sensitivity and specificity of Zika RDT in a field test was determined using positive and negative samples from Brazil and Korea. The diagnostic accuracy of Zika RDT was fairly high; sensitivity and specificity for IgG was 99.0 and 99.3%, respectively, while for IgM it was 96.7 and 98.7%, respectively. Cross reaction with dengue virus was evaluated using anti-Dengue Mixed Titer Performance Panel (PVD201), in which the Zika RDT showed cross-reactions with DENV in 16.7% and 5.6% in IgG and IgM, respectively. Cross reactions were not observed with West Nile, yellow fever, and hepatitis C virus infected sera. Zika RDT kit is very simple to use, rapid to assay, and very sensitive, and highly specific. Therefore, it would serve as a choice of method for point-of-care diagnosis and large scale surveys of ZIKV infection under clinical or field conditions worldwide in endemic areas.
Antibodies ; Antibodies, Monoclonal ; Baculoviridae ; Brazil ; Cross Reactions ; Dengue Virus ; Diagnosis ; Diagnostic Tests, Routine ; Enzyme-Linked Immunosorbent Assay ; Flavivirus ; Gold Colloid ; Hepacivirus ; Immunoglobulin G ; Immunoglobulin M ; Korea ; Methods ; Neutralization Tests ; Point-of-Care Systems ; Polymerase Chain Reaction ; Reagent Kits, Diagnostic ; Sensitivity and Specificity ; Sf9 Cells ; Yellow Fever ; Zika Virus

The recent epidemic of Zika virus in South America caused people around the world to exhibit an increased interest in the impact of arboviral illnesses. In Korea, malaria and Japanese encephalitis are the most important mosquito-borne diseases that occur indigenously. However, with the continuously increasing number of international travelers, the incidence of imported arboviral illnesses is also increasing. Currently, dengue fever is the most common mosquito-borne disease among Korean international travelers. The number of patients with Japanese encephalitis, chikungunya fever, and Zika virus infection is also on the rise. Many countries that have disease-transmitting mosquitoes have already experienced autochthonous arboviral infections due to the introduction of viruses by travelers. Moreover, with global warming and urbanization of the areas in which mosquito-borne diseases occur, the environment is becoming more favorable for mosquito-borne diseases. This concise review describes the current status and outlook of mosquito-borne diseases in Korea.
Chikungunya Fever ; Culicidae ; Dengue ; Encephalitis, Japanese ; Global Warming ; Humans ; Incidence ; Korea* ; Malaria ; South America ; Urbanization ; Zika Virus ; Zika Virus Infection