Zika Virus Research Articles

Enhancing antibody detection sensitivity in lateral flow immunoassays using endospores of Bacillus subtilis as signal amplifiers

Antibody detection is the critical first step for tracking the spread of many diseases including COVID-19. Lateral flow immunoassay (LFIA) is the most commonly used method for rapid antibody detection because it is easy-to-use and inexpensive. However, LFIA has limited sensitivity when gold nanoparticles (AuNPs) are used as the signals. In this study, the endospores of Bacillus subtilis were used in combination with AuNP in a LFIA to detect antibodies. The endospores serve as a signal amplifier. The detection limit was about 10−8 M for anti-beta galactosidase antibody detection whereas the detection limit of conventional LFIA is about 10−6 M. Furthermore, the proposed methods have no additional user steps compared with the traditional LFIA. This method, therefore, improved the sensitivity 100-fold without compromising any advantages of LFIA. We believe that the proposed method will be useful for detection of antibodies against HIV, Zika virus, SARS-CoV-2, and so on.

The interaction of GRP78 and Zika virus E and NS1 proteins occurs in a chaperone-client manner

Glucose regulated protein 78 (GRP78) is a chaperone protein that is a central mediator of the unfolded protein response, a key cellular stress response pathway. GRP78 has been shown to be critically required for infection and replication of a number of flaviviruses, and to interact with both non-structural (NS) and structural flavivirus proteins. However, the nature of the specific interaction between GRP78 and viral proteins remains largely unknown. This study aimed to characterize the binding domain and critical amino acid residues that mediate the interaction of GRP78 to ZIKV E and NS1 proteins. Recombinant EGFP fused GRP78 and individual subdomains (the nucleotide binding domain (NBD) and the substrate binding domain (SBD)) were used as a bait protein and co-expressed with full length or truncated ZIKV E and NS1 proteins in HEK293T/17 cells. Protein–protein interactions were determined by a co-immunoprecipitation assay. From the results, both the NBD and the SBD of GRP78 were crucial for an effective interaction. Single amino acid substitutions in the SBD showed that R492E and T518A mutants significantly reduced the binding affinity of GRP78 to ZIKV E and NS1 proteins. Notably, the interaction of GRP78 with ZIKV E was stably maintained against various single amino acid substitutions on ZIKV E domain III and with all truncated ZIKV E and NS1 proteins. Collectively, the results suggest that the principal binding between GRP78 and viral proteins is mainly a classic canonical chaperone protein-client interaction. The blocking of GRP78 chaperone function effectively inhibited ZIKV infection and replication in neuronal progenitor cells. Our findings reveal that GRP78 is a potential host target for anti-ZIKV therapeutics.

A Perspective on Protein Structure Prediction Using Quantum Computers.

Despite the recent advancements by deep learning methods such as AlphaFold2, in silico protein structure prediction remains a challenging problem in biomedical research. With the rapid evolution of quantum computing, it is natural to ask whether quantum computers can offer some meaningful benefits for approaching this problem. Yet, identifying specific problem instances amenable to quantum advantage and estimating the quantum resources required are equally challenging tasks. Here, we share our perspective on how to create a framework for systematically selecting protein structure prediction problems that are amenable for quantum advantage, and estimate quantum resources for such problems on a utility-scale quantum computer. As a proof-of-concept, we validate our problem selection framework by accurately predicting the structure of a catalytic loop of the Zika Virus NS3 Helicase, on quantum hardware.

Zika infection among international students after five months in Thailand.

Zika virus outbreak was traced among international students in Thailand. Testing was prompted by a single symptomatic case, which revealed seropositivity in two students. These results highlight the potential risk of Zika and emphasize the importance of implementing preventive measures for those travelling to endemic regions such as Thailand.

Antiviral Activities of Heparan Sulfate Mimetic RAFT Polymers Against Mosquito-borne Viruses.

Mosquito-borne viruses are a major worldwide health problem associated with high morbidity and mortality rates and significant impacts on national healthcare budgets. The development of antiviral drugs for both the treatment and prophylaxis of these diseases is thus of considerable importance. To address the need for therapeutics with antiviral activity, a library of heparan sulfate mimetic polymers was screened against dengue virus (DENV), Yellow fever virus (YFV), Zika virus (ZIKV), and Ross River virus (RRV). The polymers were prepared by RAFT polymerization of various acidic monomers with a target MW of 20 kDa (average Mn ∼ 27 kDa by GPC). Among the polymers, poly(SS), a homopolymer of sodium styrenesulfonate, was identified as a broad spectrum antiviral with activity against all the tested viruses and particularly potent inhibition of YFV (IC50 = 310 pM). Our results further uncovered that poly(SS) exhibited a robust inhibition of ZIKV infection in both mosquito and human cell lines, which points out the potential functions of poly(SS) in preventing mosquito-borne viruses associated diseases by blocking viral transmission in their mosquito vectors and mitigating viral infection in patients.

The pathogenicity and potential risk evaluation of Zika virus to cause mysterious "Disease X": A brief report.

Disease X is included to represent an unknown pathogen that has the potential to spread globally and trigger significant epidemics. The World Health Organization (WHO) and the Global Alliance for Vaccine and Immunization (GAVI) recommend 10 potential disease organisms responsible for disease X. Among them, the Zika virus (ZIKV) is one of the potential organisms. The present work aimed to evaluate the current pathogenicity and potential risk of the ZIKV for public health emergencies. We performed a brief review of existing literature from available sources using Zika fever, Zika virus, and Flaviviridae as keywords and extracted relevant information for this review. The primary way that the ZIKV transmits to humans is by mosquito bites (Aedes aegypti and Aedes albopictus). Typically, Aedes mosquitoes bite during the day. As an RNA virus, the ZIKV is well-known for its rapid mutation rate. ZIKV strains or variations can arise due to genomic mutations, and they occur through various processes, including replication errors, recombination, and selection pressure. Nowadays, the ZIKV has also evolved into a global pandemic because the four-amino acid sequence fits the envelope protein's 154 glycosylation motif, which may be involved in virulence. There is no specific medicine or vaccine available for the prevention or treatment of ZIKV infection. Therefore, personal protective measures should be the way to prevent ZIKV disease. Therefore, avoiding exposure is the best way to prevent problems from ZIKV to mosquitoes.

Characterization of the infectivity of an Indonesian Zika virus strain in mammalian cell lines

Objective: To characterize the infection patterns and growth characteristics of the Zika virus (ZIKV) strain JMB-185 from Indonesia in various mammalian cell lines. Methods: ZIKV was grown in human (A549, HEK293, HepG2, Huh7, Jurkat, and THP-1) and non-human mammalian (RAW264.7, Vero, and Vero76) cell lines. Viral replication kinetics were measured using plaque assay, while intra- and extracellular viral RNA concentrations were assessed using RT-PCR. Flow cytometry was used to quantify the infected cells and cell viability was measured using an MTT assay. The ability of ZIKV to infect cell lines was visualized using a fluorescence immunostaining assay. Results: This ZIKV strain preferentially infected the lung, kidney, and liver cell lines A549, HEK293, Huh7, Vero, and Vero76, but not the immune cells Jurkat, RAW264.7, and THP-1. By contrast, the ZIKV showed no sign of infection in HepG2 cells, while maintaining viral titer over 3 days post-infection, with no infection recorded in immunostaining, no increase in viral RNA, and no indication of cell deterioration. Conclusions: The Indonesian ZIKV strain has a similar infection profile as other strains, except for its poor infectivity on HepG2 cells. Information on the growth characteristics of Indonesia ZIKV will help expand our understanding of the biology of ZIKV which will be useful for various applications including antiviral discovery.

Decidual production of interferon lambda in response to ZIKV persistence: Clinical evidence and in vitro modelling

Zika virus (ZIKV) infections during pregnancy can result in Congenital Zika Syndrome (CZS), a range of severe neurological outcomes in fetuses that primarily occur during early gestational stages possibly due to placental damage. Although some placentas can maintain ZIKV persistence for weeks or months after the initial infection and diagnosis, the impact of this viral persistence is still unknown. Here, we aimed to investigate the immunological repercussion of ZIKV persistence in term placentas. As such, term placentas from 64 pregnant women diagnosed with Zika in different gestational periods were analyzed by ZIKV RT-qPCR, examination of decidua and placental villous histopathology, and expression of inflammation-related genes and IFNL1-4. Subsequently, we explored primary cultures of term decidual Extravillous Trophoblasts (EVTs) and Term Chorionic Villi (TCV) explants, as in vitro models to access the immunological consequences of placental ZIKV infection. Placenta from CZS cases presented low IFNL1-4 expression, evidencing the critical protective role of theses cytokines in the clinical outcome. Term placentas cleared for ZIKV showed increased levels of IFNL1, 3, and 4, whether viral persistence was related with a proinflammatory profile. Conversely, upon ZIKV persistence placentas with decidual inflammation showed high IFNL1-4 levels. In vitro experiments showed that term EVTs are more permissive, and secreted higher levels of IFN-α2 and IFN-λ1 compared to TCV explants. The results suggest that, upon ZIKV persistence, the maternal-skewed decidua contributes to placental inflammatory and antiviral signature, through chronic deciduitis and IFNL upregulation. Although further studies are needed to elucidate the mechanisms underlying the decidual responses against ZIKV. Hence, this study presents unique insights and valuable in vitro models for evaluating the immunological landscape of placentas upon ZIKV persistence.

A high-throughput cell-based screening method for Zika virus protease inhibitor discovery

Zika virus (ZIKV) continues to pose a significant global public health threat, with recurring regional outbreaks and potential for pandemic spread. Despite often being asymptomatic, ZIKV infections can have severe consequences, including neurological disorders and congenital abnormalities. Unfortunately, there are currently no approved vaccines or antiviral drugs for the prevention or treatment of ZIKV. One promising target for drug development is the ZIKV NS2B-NS3 protease due to its crucial role in the virus life cycle. In this study, we established a cell-based ZIKV protease inhibition assay designed for high-throughput screening (HTS). Our assay relies on the ZIKV protease's ability to cleave a cyclised firefly luciferase fused to a natural cleavage sequence between NS2B and NS3 protease within living cells. We evaluated the performance of our assay in HTS setting using the pharmacologic controls (JNJ-40418677 and MK-591) and by screening a Library of Pharmacologically Active Compounds (LOPAC). The results confirmed the feasibility of our assay for compound library screening to identify potential ZIKV protease inhibitors.

High prevalence of dengue, Zika, and chikungunya viruses in blood donors during a dengue outbreak and an endemic period in Colombia.

Arboviruses pose a challenge in ensuring the supply of pathogen-free blood components because they are not routinely screened in blood banks, and blood components from infected asymptomatic donors could be transfused. This study aimed to detect and characterize arboviral infections in Colombian blood donors. In a cross-sectional study, the prevalence of dengue (DENV), Zika (ZIKV), and chikungunya (CHIKV) viruses and co-infections of blood donors were compared between an epidemic period (November 2019-February 2020, n = 462) and an endemic period (November 2021-August 2022, n = 1,119). Viral RNA from each donor serum was purified, and the viruses were detected using a previously standardized multiplex hemi-nested RT-PCR protocol. Subsequently, donors who tested positive were surveyed 15 days after the detection of the virus to identify clinical characteristics related to the arboviral infection. The prevalences of each virus were presented as percentages and compared between epidemic and endemic periods. Significantly higher prevalences were found in the epidemic period compared with the endemic period for DENV (14.5 vs. 1.9%), ZIKV (7.8 vs. 0.3%), CHIKV (8 vs. 3.3%), and co-infections (4.3 vs. 0.2%). The survey response rate of positive donors in the two periods was 83/175 (47%). In total, 57% of the donors surveyed were asymptomatic. Symptomatic donors most frequently reported headache (31%), malaise (13%), arthralgia (10%), and fever/chills (8%). The prevalence observed in epidemic and endemic periods was higher than that reported in other studies in the Americas. The high proportion of asymptomatic cases found, in addition to the mild and nonspecific manifestations among the symptomatic, may limit the effectiveness of the donor selection criteria used to mitigate the risk of transfusion-transmitted arboviruses.

Design of antiviral AGO2-dependent short hairpin RNAs

The increasing emergence and re-emergence of RNA virus outbreaks underlines the urgent need to develop effective antivirals. RNA interference (RNAi) is a sequence-specific gene silencing mechanism that is triggered by small interfering RNAs (siRNAs) or short hairpin RNAs (shRNAs), which exhibits significant promise for antiviral therapy. AGO2-dependent shRNA (agshRNA) generates a single-stranded guide RNA and presents significant advantages over traditional siRNA and shRNA. In this study, we applied a logistic regression algorithm to a previously published chemically siRNA efficacy dataset and built a machine learning-based model with high predictive power. Using this model, we designed siRNA sequences targeting diverse RNA viruses, including human enterovirus A71 (EV71), Zika virus (ZIKV), dengue virus 2 (DENV2), mouse hepatitis virus (MHV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and transformed them into agshRNAs. We validated the performance of our agshRNA design by evaluating antiviral efficacies of agshRNAs in cells infected with different viruses. Using the agshRNA targeting EV71 as an example, we showed that the anti-EV71 effect of agshRNA was more potent compared with the corresponding siRNA and shRNA. Moreover, the antiviral effect of agshRNA is dependent on AGO2-processed guide RNA, which can load into the RNA-induced silencing complex (RISC). We also confirmed the antiviral effect of agshRNA in vivo. Together, this work develops a novel antiviral strategy that combines machine learning-based algorithm with agshRNA design to custom design antiviral agshRNAs with high efficiency.

Microalgae-made human vaccines and therapeutics: A decade of advances.

Microalgal emergence is a promising platform with two-decade historical background for producing vaccines and biopharmaceuticals. During that period, microalgal-based vaccines have reported successful production for various diseases. Thus, species selection is important for genetic transformation and delivery methods that have been developed. Although many vaccine prototypes have been produced for infectious and non-infectious diseases, fewer studies have reached immunological and immunoprotective evaluations. Microalgae-made vaccines for Staphylococcus aureus, malaria, influenza, human papilloma, and Zika viruses have been explored in their capacity to induce humoral or cellular immune responses and protective efficacies against experimental challenges. Therefore, specific pathogen antigens and immune system role are important and addressed in controlling these infections. Regarding non-communicable diseases, these vaccines have been investigated for breast cancer; microalgal-produced therapeutic molecules and microalgal-made interferon-α have been explored for hypertension and potential applications in treating viral infections and cancer, respectively. Thus, conducting immunological trials is emphasized, discussing the promising results observed in terms of immunogenicity, desired immune response for controlling affections, and challenges for achieving the desired protection levels. The potential advantages and hurdles associated with this innovative approach are highlighted, underlining the relevance of assessing immune responses in preclinical and clinical trials to validate the efficacy of these biopharmaceuticals. The promising future of this healthcare technology is also envisaged.

Histological validation of in-vivo larvicidal efficacy of marine Streptomyces sp. RD06 secondary metabolites against filariasis causing Culex quinquefasciatus and statistical media optimization for larvicidal derivatives production

Mosquito-borne disease pandemics, such as the Zika virus and chikungunya, have escalated cognizance of how critical it is to implement proficient mosquito vector control measures. The prevention of Culicidae is becoming more difficult these days because of the expeditious imminence of synthetic pesticide resistance and the universal expansion of tremendously invasive mosquito vectors. The present study highlights the insecticidal and larvicidal efficacy of the prospective novel actinobacterium derived from the marine Streptomyces sp. RD06 secondary metabolites against Culex quinquefasciatus mosquito. The pupicidal activity of Streptomyces sp. RD06 showed LC50=199.22 ± 11.54 and LC90= 591.84 ± 55.41 against the pupa. The purified bioactive metabolites 1, 2-Benzenedicarboxylic acid, diheptyl ester from Streptomyces sp. RD06 exhibited an LC50 value of 154.13 ± 10.50 and an LC90 value of 642.84 ± 74.61 tested against Cx. quinquefasciatus larvae. The Streptomyces sp. RD06 secondary metabolites exhibited 100 % non-hatchability at 62.5 ppm, and 82 % of hatchability was observed at 250 ppm. In addition, media optimization showed that the highest biomass production was attained at a temperature of 41.44 °C, pH 9.23, nitrogen source 11.43 mg/ml, and carbon source 150 mg/ml. Compared to control larvae, the histology and confocal microscopy results showed destruction to the anal gill, lumen content, and epithelial layer residues in the treated larvae. Utilizing an eco-friendly method, these alternative inventive insecticidal derivatives from Streptomyces sp. RD06 eradicates Culex quinquefasciatus. This study highlights the promising potential of these Streptomyces sp. RD06 secondary metabolites to develop affordable and efficacious mosquito larvicides to replace synthetic insecticides in the future.

Development in the Inhibition of Dengue Proteases as Drug Targets.

Viral infections continue to increase morbidity and mortality severely. The flavivirus genus has fifty different species, including the dengue, Zika, and West Nile viruses that can infect 40% of individuals globally, who reside in at least a hundred different countries. Dengue, one of the oldest and most dangerous human infections, was initially documented by the Chinese Medical Encyclopedia in the Jin period. It was referred to as "water poison," connected to flying insects, i.e., Aedes aegypti and Aedes albopictus. DENV causes some medical expressions like dengue hemorrhagic fever, acute febrile illness, and dengue shock syndrome. According to the World Health Organization report of 2012, 2500 million people are in danger of contracting dengue fever worldwide. According to a recent study, 96 million of the 390 million dengue infections yearly show some clinical or subclinical severity. There is no antiviral drug or vaccine to treat this severe infection. It can be controlled by getting enough rest, drinking plenty of water, and using painkillers. The first dengue vaccine created by Sanofi, called Dengvaxia, was previously approved by the USFDA in 2019. All four serotypes of the DENV1-4 have shown re-infection in vaccine recipients. However, the usage of Dengvaxia has been constrained by its adverse effects. Different classes of compounds have been reported against DENV, such as nitrogen-containing heterocycles (i.e., imidazole, pyridine, triazoles quinazolines, quinoline, and indole), oxygen-containing heterocycles (i.e., coumarins), and some are mixed heterocyclic compounds of S, N (thiazole, benzothiazine, and thiazolidinediones), and N, O (i.e., oxadiazole). There have been reports of computationally designed compounds to impede the molecular functions of specific structural and non-structural proteins as potential therapeutic targets. This review summarized the current progress in developing dengue protease inhibitors.

Development and assessment of a multiepitope synthetic antigen for the diagnosis of Dengue virus infection

Immunodiagnostic tests for detecting dengue virus infections encounter challenges related to cross-reactivity with other related flaviviruses. Our research focuses on the development of a synthetic multiepitope antigen tailored for dengue immunodiagnostics. Selected dengue epitopes involved structural linearity and dissimilarity from the proteomes of Zika and Yellow fever viruses which served for computationally modeling the three-dimensional protein structure, resulting in the design of two proteins: rDME-C and rDME-BR. Both proteins consist of seven epitopes, separated by the GPGPG linker, and a carboxy-terminal 6 × -histidine tag. The molecular weights of the final proteins rDME-C and rDME-BR are 16.83 kDa and 16.80 kDa, respectively, both with an isoelectric point of 6.35. The distinguishing factor between the two proteins lies in the origin of their epitope sequences, where rDME-C is based on the reference dengue proteome, while rDME-BR utilizes sequences from prevalent Dengue genotypes in Brazil from 2008 to 2019. PyMol analysis revealed exposure of epitopes in the secondary structure. Successful expression of the antigens was achieved in soluble form and fluorescence experiments indicated a disordered structure. In subsequent testing, rDME-BR and rDME-C antigens were assessed using an indirect Elisa protocol against Dengue infected serum, previously examined with a commercial diagnostic test. Optimal concentrations for antigens were determined at 10 µg/mL for rDME-BR and 30 µg/mL for rDME-C, with serum dilutions ranging from 1:50 to 1:100. Both antigens effectively detected IgM and IgG antibodies in Dengue fever patients, with rDME-BR exhibiting higher sensitivity. Our in-house test showed a sensitivity of 77.3 % and 82.6 % and a specificity of 89.4 % and 71.4 % for rDME-C and rDEM-BR antigens. No cross-reactivity was observed with serum from Zika-infected mice but with COVID-19 serum samples. Our findings underscore the utility of synthetic biology in crafting Dengue-specific multiepitope proteins and hold promise for precise clinical diagnosis and monitoring responses to emerging Dengue vaccines.

In vitro enhancement of Zika virus infection by preexisting West Nile virus antibodies in human plasma-derived immunoglobulins revealed after P2 binding site-specific enrichment.

Human immunoglobulin preparations contain a diverse range of polyclonal antibodies that reflect past immune responses against pathogens encountered by the blood donor population. In this study, we examined a panel of intravenous immunoglobulins (IGIVs) manufactured over the past two decades (1998-2020) for their capacity to neutralize or enhance Zika virus (ZIKV) infection in vitro. These IGIVs were selected specifically based on their production dates in relation to the occurrences of two flavivirus outbreaks in the U.S.: the West Nile virus (WNV) outbreak in 1999 and the ZIKV outbreak in 2015. As demonstrated by enzyme-linked immunosorbent assay (ELISA) experiments, IGIVs made before the ZIKV outbreak already harbored antibodies that bind to various peptides across the envelope protein of ZIKV because of the WNV outbreak. Using phage display, the most dominant binding site was mapped precisely to the P2 peptide between residues 211 and 230 within domain II, where BF1176-56, an anti-ZIKV monoclonal antibody, also binds. When tested in permissive Vero E6 cells for ZIKV neutralization, the IGIVs, even after undergoing rigorous enrichment for P2 binding specificity, failed, as did BF1176-56. Meanwhile, BF1176-56 enhanced ZIKV infection in both FcγRII-expressing K562 cells and human peripheral blood mononuclear cells. However, for enhancement by the IGIVs to be detected in these cells, a substantial increase in their P2 binding specificity was required, thus linking the P2 site with ZIKV enhancement in vitro. Our findings warrant further study of the significance of elevated levels of anti-WNV antibodies in IGIVs, considering that various mechanisms operating in vivo may modulate ZIKV infection outcomes.IMPORTANCEWe investigated the capacity of intravenous immunoglobulins manufactured previously over two decades (1998-2020) to neutralize or enhance Zika virus infection in vitro. West Nile virus antibodies in IGIVs could not neutralize Zika virus initially; however, once the IGIVs were concentrated further, they enhanced its infection. These findings lay the groundwork for exploring how preexisting WNV antibodies in IGIVs could impact Zika infection, both in vitro and in vivo. Our observations are historically significant, since we tested a panel of IGIV lots that were carefully selected based on their production dates which covered two major flavivirus outbreaks in the U.S.: the WNV outbreak in 1999 and the ZIKV outbreak in 2015. These findings will facilitate our understanding of the interplay among closely related viral pathogens, particularly from a historical perspective regarding large blood donor populations. They should remain relevant for future outbreaks of emerging flaviviruses that may potentially affect vulnerable populations.

Antiviral drug discovery: Pyrimidine entry inhibitors for Zika and dengue viruses

Vector-borne diseases, constituting over 17 % of infectious diseases, are caused by parasites, viruses, and bacteria, and their prevalence is shaped by environmental and social factors. Dengue virus (DENV) and Zika virus (ZIKV), some of the most prevalent infectious agents of this type of diseases, are transmitted by mosquitoes belonging to the genus Aedes. The highest prevalence is observed in tropical regions, inhabited by around 3 billion people. DENV infects millions of people annually and constitutes an additional sanitary challenge due to the circulation of four serotypes, which has complicated vaccine development. ZIKV causes large outbreaks globally and its infection is known to lead to severe neurological diseases, including microcephaly in newborns. Besides, not only mosquito control programs have proved to be not totally effective, but also, no antiviral drugs have been developed so far. The envelope protein (E) is a major component of DENV and ZIKV virion surface. This protein plays a key role during the virus cell entry, constituting an attractive target for the development of antiviral drugs. Our previous studies have identified two pyrimidine analogs (3e and 3h) as inhibitors; however, their activity was found to be hindered by their low water solubility. In this study, we performed a low-throughput antiviral screening, revealing compound 16a as a potent DENV-2 and ZIKV inhibitor (EC50 = 1.4 μM and 2.4 μM, respectively). This work was aimed at designing molecules with improved selectivity and pharmacokinetic properties, thus advancing the antiviral efficacy of compounds for potential therapeutic use.

Water, mosquitoes, and sugar

Songkran, the new year and water splashing festival during 11-17 April, was the peak of road accidents in Thailand which now ranks number one in the world, COVID-19, and influenza. After Songkran was the World Malaria Day on 25 April. Thailand is striving to eliminate malaria as well as other mosquitoes-borne infectious diseases including Dengue fever and Zika virus. In addition to infectious diseases, Thailand is also facing with non-communicable diseases caused by excessive sugar consumption and smoking which currently appeared in a new form, the electronic version.

An Update on Zika Virus Vaccine Development and New Research Approaches

Zika virus (ZIKV) is an emerging flavivirus that represents significant public health challenges, particularly in the Americas, and is a substantial risk to other parts of the world due to its rapid expansion and its established association with neurological disorders, including Guillain–Barré syndrome and an intrauterine fetal infection that can cause microcephaly, blindness, and other congenital neurological complications. To date, no vaccine to prevent ZIKV infections has been approved. Therefore, developing a safe and effective vaccine against this virus is a global health priority. This review analyzes the ZIKV outbreaks, as well as associated neurological complications, its genome, and immunological responses. The current vaccines in development have reported results from preclinical and clinical trials about novel approaches to obtain safer and more effective vaccines and the challenges faced by ZIKV vaccine development.

Acquiring insights through a sequence-based approach to the critical Zika virus MTase domain

Background: ZIKV is one of the re-emerging arboviruses (viruses carried by arthropods), which is spread through the Aedes mosquito. It is an RNA virus with only one strand that is appropriate to the family Flaviviridae's Flavivirus (genus) & has been linked to other Flaviviruses such as the West Nile virus, chikungunya virus, & dengue (DENV) virus. The envelope, precursor membrane, and capsid are three structural proteins, and seven nonstructural proteins are also encoded by the Zika virus genome.Methods: We conducted an in-silico analysis of the Zika virus' MTase domain protein for this publication. We predicted that methylation would play a significant role in the available Prosite, Pfam, and InterProScan tools to aid in locating the MTase domain. Along with alignment, amino acid composition, charged amino acids, atomic level studies, & molecular weight, we also make predictions for these variables, including theoretical Pi.Results: We also examine the MTase domain's simulated structure (alpha helix, beta sheet, turn) and its specifics, including secondary structure. We also pinpoint the locations where proteins, DNA, and RNA bind. Potential phosphorylation sites can be found on the Ser, Thr, and Tyr residues in the MTase domain.Conclusion: These outcomes imply a complicated interaction between different phosphorylation modifications that modulates the activity of the MTase domain. To fully appreciate the auxiliary and practical perspectives and to clarify the varied roles of PTM in the MTase domain will be a primary goal of future study.Keywords: I-TASSER; Secondary structure; Prosite; α-helix; Pfam; InterProScan; Binding sites; Posttranslational modification; SOPMA; Phyre2