Displaying publications 1 - 20 of 350 in total

Abstract:
Sort:
  1. Serum Stabilities and Antiviral Activities of Chemically Modified Peptides Against Dengue Serotypes 1-4
    Lee MF, Anasir MI, Poh CL
    J Pharm Sci, 2024 Mar;113(3):587-595.
    PMID: 38103687 DOI: 10.1016/j.xphs.2023.12.009
    Dengue presents a major public health concern in over 100 countries due to the absence of an effective vaccine and antiviral therapy against all four dengue virus (DENV) serotypes. Several antiviral peptides were previously reported to inhibit at least three or all four DENV serotypes. Chemical modifications such as d-amino acid substitutions, polyethylene glycol (PEG)ylation, and cyclization could be applied to peptides to improve their biological activities and stability in serum. The PEGylated peptide 3 (PEG-P3) was identified to be the most promising antiviral candidate as it demonstrated good inhibitory effects against all four DENV serotypes during the pre- and post-infection stages, Based on the RP-HPLC and LC/MS analysis, peptide 4 was identified to be more stable in human serum than peptide 3, with 78.9 % and 41.6 % of the peptides remaining after 72 h of incubation in human serum, respectively. Both peptides were also able to retain their antiviral activities against specific DENV serotypes after 72 h incubation in human serum. PEG-P3 was found to be more stable than the unmodified peptide 3 with 89.4 % of PEG-P3 remaining in the human serum after 72 h of incubation. PEG-P3 was able to retain its inhibitory effects against DENV-1 to 4 after 72 h of incubation in human serum. This study provided insights into the antiviral activities and stabilities of the unmodified and chemically modified peptides in human serum.
    Matched MeSH terms: Dengue Virus*
  2. Fulltext Site-specific imprinting of dengue virus non-structural 1 antigen on a polydopamine-based sensing film for early detection and prognosis of dengue
    Lim HJ, Saha T, Ooi CW
    Talanta, 2024 Feb 01;268(Pt 2):125376.
    PMID: 37951180 DOI: 10.1016/j.talanta.2023.125376
    Serum levels of dengue virus (DENV) non-structural 1 (NS1) antigen can serve as a valuable prognostic indicator of severe dengue infections. A quartz crystal microbalance (QCM)-based biosensor with a biomimetic recognition element was designed to quantitatively detect DENV NS1 as an early disease biomarker. To mitigate the reliance on costly viral antigens during the molecular imprinting process, a synthetic peptide mimicking a DENV NS1 epitope was used as a surrogate template for the synthesis of an epitope-imprinted polydopamine (EMIPDA) sensing film on the biosensor surface. The maximal frequency shift for DENV NS1 was obtained with an EMIPDA film synthesised using 5 mg mL-1 of dopamine monomer and 0.5 mg mL-1 of peptide template. The EMIPDA-QCM biosensor achieved low detection and quantitation limits of 0.091 μg mL-1 and 0.436 μg mL-1, respectively, allowing acute-phase detection of dengue and prognosis of the disease progression. The EMIPDA-QCM biosensor exhibited remarkable selectivity with up to 68-fold larger frequency responses towards DENV NS1 compared to a major serum protein. The site-specific imprinting approach not only enhanced the biosensing performance but also enabled a 26-fold cost reduction for biosensor functionalisation, providing a cost-effective strategy for label-free biosensing of the dengue biomarker via the biopolymer film.
    Matched MeSH terms: Dengue Virus*
  3. Dengue and zika seropositivity, burden, endemicity, and cocirculation antibodies in Nigeria
    Asaga Mac P, Tadele M, Airiohuodion PE, Nisansala T, Zubair S, Aigohbahi J, et al.
    Ann Med, 2023 Dec;55(1):652-662.
    PMID: 37074313 DOI: 10.1080/07853890.2023.2175903
    INTRODUCTION: Mosquito-borne infections are of global health concern because of their rapid spread and upsurge, which creates a risk for coinfections. DENV and ZIKV are transmitted by Aedes aegypti and A. albopictus and are prevalent in Nigeria and neighbouring countries. However, their seroprevalence, burden, hidden endemicity and possible cocirculation are poorly understood in Nigeria.

    METHODS: We conducted a cross-sectional study of 871 participants from three regions of Nigeria. All serum samples were analysed using malaria RDT and the immunoblot molecular diagnostic assay recomLine Tropical Fever for the presence of arboviral antibody serological marker IgG (Mikrogen Diagnostik, Neuried, Germany) with DENV and ZIKV Nonstructural protein 1 (NS 1), DENV and ZIKV Equad (variant of the envelope protein with designated mutations to increase specificity), according to the manufacturer's instructions.

    RESULTS: The overall IgG antibody seropositivity against DENV-flavivirus was 44.7% (389/871); 95% CI (41.41-47.99), while ZIKV-flavivirus was 19.2% (167/871); 95% CI (0.16-0.21), and DENV-ZIKV-flavivirus cocirculation antibody seropositivity was 6.2%5 (54/871); 95% CI (0.6-0.7) in the three study regions of Nigeria. The study cohort presented similar clinical signs and symptoms of flaviviruses (DENV and ZIKV) in all three study regions.

    CONCLUSION: This study highlighted an unexpectedly high antibody seropositivity, burden, hidden endemicity, and regional spread of mono- and co-circulating flaviviruses (DENV and ZIKV) in Nigeria.Key messagesDengue flavivirus sero-cross-reactivity drives antibody-dependent enhancement of ZIKV infection.Both viruses share common hosts (humans) and vectors (primarily Aedes aegypti), and are thus influenced by similar biological, ecological, and economic factors, resulting in epidemiological synergy.Additionally, the actual burden in epidemic and interepidemic periods is grossly or chronically unknown and underreported. Despite this trend and the potential public health threat, there are no reliable data, and little is known about these arboviral co-circulation infections.

    Matched MeSH terms: Dengue Virus*
  4. In silico screening of plant peptides against the envelope protein of dengue virus
    Reena G, Ranjani R, Goutham KD, Sangeetha K
    Trop Biomed, 2023 Jun 01;40(2):124-128.
    PMID: 37650397 DOI: 10.47665/tb.40.2.001
    Peptide therapeutics are found to be an emerging and attractive class of treatment due to their highly specific and safe nature. Hence twenty plant peptides were subjected to screening by molecular docking against the envelope protein of the dengue virus using Clus Pro, Patch Dock, and HADDOCK servers. Physicochemical parameters, allergenicity, and toxicity profile of the plant peptides were estimated by Protparam analysis, AllergenFP, and ToxinPred web servers. Six potential compounds namely Ginkbilobin, Cycloviolin-D, Circulin-B, Circulin-A, Cycloviolacin-013, and Circulin-C showed the highest binding energy with both nonallergenic and nontoxic properties. They also exhibited desirable half-lives extending to 30 hrs except for Ginkbilobin, which showed the least half-life of 4.4 hours and non-polar activity. The residues of Ala-4 of Ginkbilobin; Arg-30 of Cycloviolin D; Arg-29 of Circulin A and C interacted with the Try 101 of the domain II of Envelope protein, implying the possible inhibition of the insertion process of the trimeric E protein during fusion with the host cells. Thus, the identified plant peptides could serve as potential leads upon further subjection to in vitro studies.
    Matched MeSH terms: Dengue Virus*
  5. Evaluation of an Immunoglobulin E Capture Enzyme-Linked Immunosorbent Assay for the Early Diagnosis of Dengue
    Machain-Williams C, Reyes-Solis GC, Blitvich BJ, Laredo-Tiscareño V, Dzul-Rosado AR, Kim S, et al.
    Viral Immunol, 2023 Mar;36(2):101-109.
    PMID: 36862827 DOI: 10.1089/vim.2022.0110
    Dengue virus (DENV) is the etiological agent of dengue, the most important mosquito-transmitted viral disease of humans worldwide. Enzyme-linked immunosorbent assays (ELISAs) designed to detect DENV IgM are commonly used for dengue diagnosis. However, DENV IgM is not reliably detected until ≥4 days after illness onset. Reverse transcription-polymerase chain reaction (RT-PCR) can diagnose early dengue but requires specialized equipment, reagents, and trained personnel. Additional diagnostic tools are needed. Limited work has been performed to determine whether IgE-based assays can be used for the early detection of vector-borne viral diseases, including dengue. In this study, we determined the efficacy of a DENV IgE capture ELISA for the detection of early dengue. Sera were collected within the first 4 days of illness onset from 117 patients with laboratory-confirmed dengue, as determined by DENV-specific RT-PCR. The serotypes responsible for the infections were DENV-1 and DENV-2 (57 and 60 patients, respectively). Sera were also collected from 113 dengue-negative individuals with febrile illness of undetermined etiology and 30 healthy controls. The capture ELISA detected DENV IgE in 97 (82.9%) confirmed dengue patients and none of the healthy controls. There was a high false positivity rate (22.1%) among the febrile non-dengue patients. In conclusion, we provide evidence that IgE capture assays have the potential to be explored for early diagnosis of dengue, but further research is necessary to address the possible false positivity rate among patients with other febrile illnesses.
    Matched MeSH terms: Dengue Virus/immunology
  6. Fulltext Dengue virus infection - a review of pathogenesis, vaccines, diagnosis and therapy
    Kok BH, Lim HT, Lim CP, Lai NS, Leow CY, Leow CH
    Virus Res, 2023 Jan 15;324:199018.
    PMID: 36493993 DOI: 10.1016/j.virusres.2022.199018
    The transmission of dengue virus (DENV) from an infected Aedes mosquito to a human, causes illness ranging from mild dengue fever to fatal dengue shock syndrome. The similar conserved structure and sequence among distinct DENV serotypes or different flaviviruses has resulted in the occurrence of cross reaction followed by antibody-dependent enhancement (ADE). Thus far, the vaccine which can provide effective protection against infection by different DENV serotypes remains the biggest hurdle to overcome. Therefore, deep investigation is crucial for the potent and effective therapeutic drugs development. In addition, the cross-reactivity of flaviviruses that leads to false diagnosis in clinical settings could result to delay proper intervention management. Thus, the accurate diagnostic with high specificity and sensitivity is highly required to provide prompt diagnosis in respect to render early treatment for DENV infected individuals. In this review, the recent development of neutralizing antibodies, antiviral agents, and vaccine candidates in therapeutic platform for DENV infection will be discussed. Moreover, the discovery of antigenic cryptic epitopes, principle of molecular mimicry, and application of single-chain or single-domain antibodies towards DENV will also be presented.
    Matched MeSH terms: Dengue Virus*
  7. Unusual co-infection of severe malaria by Plasmodium vivax and dengue virus in Mexico
    Queb-Pech NM, Núñez-Oreza LA, Estrada-Méndez A, Tamay-Segovia P, Collí-Heredia JP, Blum-Domínguez SC
    Trop Biomed, 2022 Dec 01;39(4):575-578.
    PMID: 36602218 DOI: 10.47665/tb.39.4.014
    Malaria and dengue fever are among the most common mosquito-borne diseases worldwide; however, reports of coinfection are rare. We present a case of severe malaria and dengue coinfection in a 16-yearold female patient presenting with fever, thrombocytopenia, pleural effusion, myopericarditis, and acute respiratory distress syndrome. Dengue infection was confirmed by the presence of immunoglobin M antibodies and nonstructural protein 1, while malaria was confirmed by the presence of Plasmodium vivax in thick and thin blood smears. This is the first report of a dengue/malaria coinfection in Mexico.
    Matched MeSH terms: Dengue Virus*
  8. Fulltext Genomic and Phenotypic Comparisons Reveal Distinct Variants of Wolbachia Strain wAlbB
    Martinez J, Ross PA, Gu X, Ant TH, Murdochy SM, Tong L, et al.
    Appl Environ Microbiol, 2022 Nov 22;88(22):e0141222.
    PMID: 36318064 DOI: 10.1128/aem.01412-22
    The intracellular bacterium Wolbachia inhibits virus replication and is being harnessed around the world to fight mosquito-borne diseases through releases of mosquitoes carrying the symbiont. Wolbachia strains vary in their ability to invade mosquito populations and suppress viruses in part due to differences in their density within the insect and associated fitness costs. Using whole-genome sequencing, we demonstrate the existence of two variants in wAlbB, a Wolbachia strain being released in natural populations of Aedes aegypti mosquitoes. The two variants display striking differences in genome architecture and gene content. Differences in the presence/absence of 52 genes between variants include genes located in prophage regions and others potentially involved in controlling the symbiont's density. Importantly, we show that these genetic differences correlate with variation in wAlbB density and its tolerance to heat stress, suggesting that different wAlbB variants may be better suited for field deployment depending on local environmental conditions. Finally, we found that the wAlbB genome remained stable following its introduction in a Malaysian mosquito population. Our results highlight the need for further genomic and phenotypic characterization of Wolbachia strains in order to inform ongoing Wolbachia-based programs and improve the selection of optimal strains in future field interventions. IMPORTANCE Dengue is a viral disease transmitted by Aedes mosquitoes that threatens around half of the world population. Recent advances in dengue control involve the introduction of Wolbachia bacterial symbionts with antiviral properties into mosquito populations, which can lead to dramatic decreases in the incidence of the disease. In light of these promising results, there is a crucial need to better understand the factors affecting the success of such strategies, in particular the choice of Wolbachia strain for field releases and the potential for evolutionary changes. Here, we characterized two variants of a Wolbachia strain used for dengue control that differ at the genomic level and in their ability to replicate within the mosquito. We also found no evidence for the evolution of the symbiont within the 2 years following its deployment in Malaysia. Our results have implications for current and future Wolbachia-based health interventions.
    Matched MeSH terms: Dengue Virus*
  9. Fulltext Design, Synthesis, and in-vitro Protease Inhibition Assay of Linear Pentapeptides as Potential Dengue Virus NS2B/NS3 Protease Inhibitors
    Abdalsatar Abdalrazaq N, Ezleen Binti Kamarulzaman E
    Arch Razi Inst, 2022 Apr;77(2):843-852.
    PMID: 36284983 DOI: 10.22092/ARI.2022.357124.1980
    Nowadays dengue virus infection (DENV) is one of the major health complications in the world. Although DENV is an old and common disease, unfortunately, until now, there are no specific relevant treatments available for it. This study, therefore, aimed to design, as well as synthesize selective peptide inhibitors, and investigate their activity by in-vitro NS2B/NS3 protease inhibition assay. The design of the peptide ligands was based on studying the interactions with the dengue NS2B/NS3 protease using the computational docking technique in the MOE and AutoDock (version 4.2) software. To this end, the researchers designed 26 linear pentapeptides based on previous studies. It was revealed that two linear pentapeptides (i.e., GKRRK and KRRRK) are the best potential inhibitors. Furthermore, based on the findings of the two independent docking programs, the peptide GKRRK was synthesized by solid-phase peptide synthesis and its structure was confirmed. The in-vitro protease inhibitor study was conducted for these two peptides to examine their activity against the dengue virus using a protin in as a control. It was found that the designed potential peptides possess interesting inhibition against the NS2B/NS3 protease. Additionally, the findings showed that the peptide GKRRK had the highest percentage of inhibition (71.11%) at 100 µM with the IC50 of 48.87 µM; therefore, this linear peptide could serve as a good inhibitor for the DENV.
    Matched MeSH terms: Dengue Virus*
  10. Fulltext Dengue Infection - Recent Advances in Disease Pathogenesis in the Era of COVID-19
    Yong YK, Wong WF, Vignesh R, Chattopadhyay I, Velu V, Tan HY, et al.
    Front Immunol, 2022;13:889196.
    PMID: 35874775 DOI: 10.3389/fimmu.2022.889196
    The dynamics of host-virus interactions, and impairment of the host's immune surveillance by dengue virus (DENV) serotypes largely remain ambiguous. Several experimental and preclinical studies have demonstrated how the virus brings about severe disease by activating immune cells and other key elements of the inflammatory cascade. Plasmablasts are activated during primary and secondary infections, and play a determinative role in severe dengue. The cross-reactivity of DENV immune responses with other flaviviruses can have implications both for cross-protection and severity of disease. The consequences of a cross-reactivity between DENV and anti-SARS-CoV-2 responses are highly relevant in endemic areas. Here, we review the latest progress in the understanding of dengue immunopathogenesis and provide suggestions to the development of target strategies against dengue.
    Matched MeSH terms: Dengue Virus*
  11. Fulltext Host immune response against DENV and ZIKV infections
    Sekaran SD, Ismail AA, Thergarajan G, Chandramathi S, Rahman SKH, Mani RR, et al.
    Front Cell Infect Microbiol, 2022;12:975222.
    PMID: 36159640 DOI: 10.3389/fcimb.2022.975222
    Dengue is a major public health concern, affecting almost 400 million people worldwide, with about 70% of the global burden of disease in Asia. Despite revised clinical classifications of dengue infections by the World Health Organization, the wide spectrum of the manifestations of dengue illness continues to pose challenges in diagnosis and patient management for clinicians. When the Zika epidemic spread through the American continent and then later to Africa and Asia in 2015, researchers compared the characteristics of the Zika infection to Dengue, considering both these viruses were transmitted primarily through the same vector, the Aedes aegypti female mosquitoes. An important difference to note, however, was that the Zika epidemic diffused in a shorter time span compared to the persisting feature of Dengue infections, which is endemic in many Asian countries. As the pathogenesis of viral illnesses is affected by host immune responses, various immune modulators have been proposed as biomarkers to predict the risk of the disease progression to a severe form, at a much earlier stage of the illness. However, the findings for most biomarkers are highly discrepant between studies. Meanwhile, the cross-reactivity of CD8+ and CD4+ T cells response to Dengue and Zika viruses provide important clues for further development of potential treatments. This review discusses similarities between Dengue and Zika infections, comparing their disease transmissions and vectors involved, and both the innate and adaptive immune responses in these infections. Consideration of the genetic identity of both the Dengue and Zika flaviviruses as well as the cross-reactivity of relevant T cells along with the actions of CD4+ cytotoxic cells in these infections are also presented. Finally, a summary of the immune biomarkers that have been reported for dengue and Zika viral infections are discussed which may be useful indicators for future anti-viral targets or predictors for disease severity. Together, this information appraises the current understanding of both Zika and Dengue infections, providing insights for future vaccine design approaches against both viruses.
    Matched MeSH terms: Dengue Virus*
  12. Fulltext Lactococcus lactis Strain Plasma Intake Suppresses the Incidence of Dengue Fever-like Symptoms in Healthy Malaysians: A Randomized, Double-Blind, Placebo-Controlled Trial
    Khor CS, Tsuji R, Lee HY, Nor'e SS, Sahimin N, Azman AS, et al.
    Nutrients, 2021 Dec 16;13(12).
    PMID: 34960061 DOI: 10.3390/nu13124507
    Dengue fever (DF) is a mosquito-borne disease still with no effective treatment or vaccine available. A randomized, placebo-controlled, double-blinded, parallel-group trial was undertaken to evaluate the efficacy of oral intake of Lactococcus lactis strain plasma (LC-Plasma) on the presentation and severity of DF-like symptoms among healthy volunteers. Study participants (320) were assigned into two groups, and consumed either placebo or LC-Plasma tablets (approximately 100 billion cells/day) for 8 weeks. The clinical symptoms of DF were self-recorded through questionnaires, and exposure to DENV was determined by serum antibody and/or DENV antigen tests. No significant differences between groups were observed for exposure to DENV, or the symptomatic ratio. Results obtained showed that participants from the LC-Plasma group reported a significant reduction in the cumulative incidence days of DF-like symptoms, which include fever (p < 0.001), muscle pain (p < 0.005), joint pain (p < 0.001), and pain behind the eyes (p < 0.001), compared to that of the placebo group. Subgroup analysis revealed a significantly (p < 0.05) reduced severity score in the LC-Plasma group when study sites were separately analyzed. Overall, our findings suggest that LC-Plasma supplementation reduces the cumulative days with DF-like symptoms, and the severity of the symptoms. Daily oral intake of LC-Plasma, hence, is shown to mitigate the DF-like symptoms.
    Matched MeSH terms: Dengue Virus/immunology*
  13. Fulltext The epidemiological characteristics of dengue in high-risk areas of China, 2013-2016
    Sang S, Liu Q, Guo X, Wu D, Ke C, Liu-Helmersson J, et al.
    PLoS Negl Trop Dis, 2021 12;15(12):e0009970.
    PMID: 34928951 DOI: 10.1371/journal.pntd.0009970
    INTRODUCTION: Dengue has become a more serious human health concern in China, with increased incidence and expanded outbreak regions. The knowledge of the cross-sectional and longitudinal epidemiological characteristics and the evolutionary dynamics of dengue in high-risk areas of China is limited.

    METHODS: Records of dengue cases from 2013 to 2016 were obtained from the China Notifiable Disease Surveillance System. Full envelope gene sequences of dengue viruses detected from the high-risk areas of China were collected. Maximum Likelihood tree and haplotype network analyses were conducted to explore the phylogenetic relationship of viruses from high-risk areas of China.

    RESULTS: A total of 56,520 cases was reported in China from 2013 to 2016. During this time, Yunnan, Guangdong and Fujian provinces were the high-risk areas. Imported cases occurred almost year-round, and were mainly introduced from Southeast Asia. The first indigenous case usually occurred in June to August, and the last one occurred before December in Yunnan and Fujian provinces but in December in Guangdong Province. Seven genotypes of DENV 1-3 were detected in the high-risk areas, with DENV 1-I the main genotype and DENV 2-Cosmopolitan the secondary one. The Maximum Likelihood trees show that almost all the indigenous viruses separated into different clusters. DENV 1-I viruses were found to be clustered in Guangdong Province, but not in Fujian and Yunnan, from 2013 to 2015. The ancestors of the Guangdong viruses in the cluster in 2013 and 2014 were most closely related to strains from Thailand or Singapore, and the Guangdong virus in 2015 was most closely related to the Guangdong virus of 2014. Based on closest phylogenetic relationships, viruses from Myanmar possibly initiated further indigenous cases in Yunnan, those from Indonesia in Fujian, while viruses from Thailand, Malaysia, Singapore and Indonesia were predominant in Guangdong Province.

    CONCLUSIONS: Dengue is still an imported disease in China, although some genotypes continued to circulate in successive years. Viral phylogenies based on the envelope gene suggested periodic introductions of dengue strains into China, primarily from Southeast Asia, with occasional sustained, multi-year transmission in some regions of China.

    Matched MeSH terms: Dengue Virus/classification; Dengue Virus/genetics; Dengue Virus/isolation & purification*
  14. Fulltext Implications of a highly divergent dengue virus strain for cross-neutralization, protection, and vaccine immunity
    Chen RE, Smith BK, Errico JM, Gordon DN, Winkler ES, VanBlargan LA, et al.
    Cell Host Microbe, 2021 Nov 10;29(11):1634-1648.e5.
    PMID: 34610295 DOI: 10.1016/j.chom.2021.09.006
    Although divergent dengue viruses (DENVs) have been isolated in insects, nonhuman primates, and humans, their relationships to the four canonical serotypes (DENV 1-4) are poorly understood. One virus isolated from a dengue patient, DKE-121, falls between genotype and serotype levels of sequence divergence to DENV-4. To examine its antigenic relationship to DENV-4, we assessed serum neutralizing and protective activity. Whereas DENV-4-immune mouse sera neutralize DKE-121 infection, DKE-121-immune sera inhibit DENV-4 less efficiently. Passive transfer of DENV-4 or DKE-121-immune sera protects mice against homologous, but not heterologous, DENV-4 or DKE-121 challenge. Antigenic cartography suggests that DENV-4 and DKE-121 are related but antigenically distinct. However, DENV-4 vaccination confers protection against DKE-121 in nonhuman primates, and serum from humans immunized with a tetravalent vaccine neutralize DENV-4 and DKE-121 infection equivalently. As divergent DENV strains, such as DKE-121, may meet criteria for serotype distinction, monitoring their capacity to impact dengue disease and vaccine efficacy appears warranted.
    Matched MeSH terms: Dengue Virus/genetics*; Dengue Virus/immunology*
  15. Fulltext Antiviral activity of silymarin and baicalein against dengue virus
    Low ZX, OuYong BM, Hassandarvish P, Poh CL, Ramanathan B
    Sci Rep, 2021 10 27;11(1):21221.
    PMID: 34707245 DOI: 10.1038/s41598-021-98949-y
    Dengue is an arthropod-borne viral disease that has become endemic and a global threat in many countries with no effective antiviral drug available currently. This study showed that flavonoids: silymarin and baicalein could inhibit the dengue virus in vitro and were well tolerated in Vero cells with a half-maximum cytotoxic concentration (CC50) of 749.70 µg/mL and 271.03 µg/mL, respectively. Silymarin and baicalein exerted virucidal effects against DENV-3, with a selective index (SI) of 10.87 and 21.34, respectively. Baicalein showed a better inhibition of intracellular DENV-3 progeny with a SI of 7.82 compared to silymarin. Baicalein effectively blocked DENV-3 attachment (95.59%) to the Vero cells, while silymarin prevented the viral entry (72.46%) into the cells, thus reducing viral infectivity. Both flavonoids showed promising antiviral activity against all four dengue serotypes. The in silico molecular docking showed that silymarin could bind to the viral envelope (E) protein with a binding affinity of - 8.5 kcal/mol and form hydrogen bonds with the amino acids GLN120, TRP229, ASN89, and THR223 of the E protein. Overall, this study showed that silymarin and baicalein exhibited potential anti-DENV activity and could serve as promising antiviral agents for further development against dengue infection.
    Matched MeSH terms: Dengue Virus/drug effects*; Dengue Virus/physiology
  16. Fulltext Emergence of Genotype I of Dengue Virus Serotype 3 during a Severe Dengue Epidemic in Sri Lanka in 2017
    Ngwe Tun MM, Muthugala R, Rajamanthri L, Nabeshima T, Buerano CC, Morita K
    Jpn J Infect Dis, 2021 Sep 22;74(5):443-449.
    PMID: 33642435 DOI: 10.7883/yoken.JJID.2020.854
    During the 2017 outbreak of severe dengue in Sri Lanka, dengue virus (DENV) serotypes 2, 3, and 4 were found to be co-circulating. Our previous study of 295 patients from the National Hospital Kandy in Sri Lanka between March 2017 and January 2018 determined that the dominant infecting serotype was DENV-2. In this study, we aimed to characterize the DENV-3 strains from non-severe and severe dengue patients from our previous study population. Patients' clinical records and previous laboratory tests, including dengue-specific nonstructural protein 1 antigen rapid test and IgM-capture and IgG enzyme-linked immunosorbent assays, were analyzed together with the present results of real-time reverse transcription polymerase chain reaction and next-generation sequencing of DENV-3. Complete genome analysis determined that DENV-3 isolates belonged to 2 different clades of genotype I and were genetically close to strains from Indonesia, China, Singapore, Malaysia, and Australia. There were 16 amino acid changes among DENV-3 isolates, and a greater number of changes were found in nonstructural proteins than in structural proteins. The emergence of DENV-3 genotype I was noted for the first time in Sri Lanka. Continuous monitoring of this newly emerged genotype and other DENV serotypes and genotypes is needed to determine their effects on future outbreaks and understand the molecular epidemiology of dengue.
    Matched MeSH terms: Dengue Virus/genetics*; Dengue Virus/isolation & purification
  17. Natural DENV-2 NS2B/NS3 protease inhibitors from Myristica cinnamomea King
    Sivasothy Y, Liew SY, Othman MA, Abdul Wahab SM, Hariono M, Mohd Nawi MS, et al.
    Trop Biomed, 2021 Jun 01;38(2):79-84.
    PMID: 33973577 DOI: 10.47665/tb.38.2.044
    The NS2B/NS3 protease is crucial for the pathogenesis of the DENV. Therefore, the inhibition of this protease is considered to be the key strategy for the development of new antiviral drugs. In the present study, malabaricones C (3) and E (4), acylphenols from the fruits of Myristica cinnamomea King, have been respectively identified as moderate (27.33 ± 5.45 μM) and potent (7.55 ± 1.64 μM) DENV-2 NS2B/NS3 protease inhibitors, thus making this the first report on the DENV-2 NS2B/NS3 protease inhibitory activity of acylphenols. Based on the molecular docking studies, compounds 3 and 4 both have π-π interactions with Tyr161. While compound 3 has hydrogen bonding interactions with Gly151, Gly153 and Tyr161, compound 4 however, forms hydrogen bonds with Ser135, Asp129, Phe130 and Ile86 instead. The results from the present study suggests that malabaricones C (3) and E (4) could be employed as lead compounds for the development of new dengue antivirals from natural origin.
    Matched MeSH terms: Dengue Virus
  18. Potential severe pediatric SARS-CoV-2-induced multisystem inflammatory syndrome resembles dengue infection
    Yuliarto S, Susanto WP, Kadafi KT, Ratridewi I, Olivianto E
    Trop Biomed, 2021 Jun 01;38(2):129-133.
    PMID: 34172701 DOI: 10.47665/tb.38.2.048
    We describe a child with acute fever and abdominal pain who developed rash and edema of extremities. Blood test revealed thrombocytopenia, lymphopenia, positive dengue-IgM, and hypoalbuminemia with elevated procalcitonin. Right pleural effusion revealed from chest x-ray. Diagnosed as dengue hemorrhagic fever (DHF) grade 1, however, at 7th day of illness, altered mental status, respiratory and circulatory failure occurred. Laboratory examination showed marked thrombocytopenia, transaminitis, metabolic acidosis, elevated D-dimer, decrease fibrinogen, and elevated cardiac marker (troponin I and CKMB). The patient then developed catecholamine-resistant shock and did not survive after 48 hours. Although rapid test of SARS CoV-2 infection was negative, rapid deterioration with some unusual clinical feature suggest multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 infection. This case raises an awareness of MIS-C that clinical features resemble dengue infection.
    Matched MeSH terms: Dengue Virus
  19. Fulltext Cordycepin Inhibits Virus Replication in Dengue Virus-Infected Vero Cells
    Panya A, Songprakhon P, Panwong S, Jantakee K, Kaewkod T, Tragoolpua Y, et al.
    Molecules, 2021 May 23;26(11).
    PMID: 34071102 DOI: 10.3390/molecules26113118
    Dengue virus (DENV) infection causes mild to severe illness in humans that can lead to fatality in severe cases. Currently, no specific drug is available for the treatment of DENV infection. Thus, the development of an anti-DENV drug is urgently required. Cordycepin (3'-deoxyadenosine), which is a major bioactive compound in Cordyceps (ascomycete) fungus that has been used for centuries in Chinese traditional medicine, was reported to exhibit antiviral activity. However, the anti-DENV activity of cordycepin is unknown. We hypothesized that cordycepin exerts anti-DENV activity and that, as an adenosine derivative, it inhibits DENV replication. To test this hypothesis, we investigated the anti-DENV activity of cordycepin in DENV-infected Vero cells. Cordycepin treatment significantly decreased DENV protein at a half-maximal effective concentration (EC50) of 26.94 μM. Moreover, DENV RNA was dramatically decreased in cordycepin-treated Vero cells, indicating its effectiveness in inhibiting viral RNA replication. Via in silico molecular docking, the binding of cordycepin to DENV non-structural protein 5 (NS5), which is an important enzyme for RNA synthesis, at both the methyltransferase (MTase) and RNA-dependent RNA polymerase (RdRp) domains, was predicted. The results of this study demonstrate that cordycepin is able to inhibit DENV replication, which portends its potential as an anti-dengue therapy.
    Matched MeSH terms: Dengue Virus/drug effects*; Dengue Virus/metabolism
  20. Fulltext Rapid testing requires clinical evaluation for accurate diagnosis of dengue disease: A passive surveillance study in Southern Malaysia
    Ngim CF, Husain SMT, Hassan SS, Dhanoa A, Ahmad SAA, Mariapun J, et al.
    PLoS Negl Trop Dis, 2021 05;15(5):e0009445.
    PMID: 34014983 DOI: 10.1371/journal.pntd.0009445
    BACKGROUND: Dengue fever is the most common mosquito-borne infection worldwide where an expanding surveillance and characterization of this infection are needed to better inform the healthcare system. In this surveillance-based study, we explored the prevalence and distinguishing features of dengue fever amongst febrile patients in a large community-based health facility in southern peninsular Malaysia.

    METHODS: Over six months in 2018, we recruited 368 adults who met the WHO 2009 criteria for probable dengue infection. They underwent the following blood tests: full blood count, dengue virus (DENV) rapid diagnostic test (RDT), ELISA (dengue IgM and IgG), nested RT-PCR for dengue, multiplex qRT-PCR for Zika, Chikungunya and dengue as well as PCR tests for Leptopspira spp., Japanese encephalitis and West Nile virus.

    RESULTS: Laboratory-confirmed dengue infections (defined by positive tests in NS1, IgM, high-titre IgG or nested RT-PCR) were found in 167 (45.4%) patients. Of these 167 dengue patients, only 104 (62.3%) were positive on rapid diagnostic testing. Dengue infection was significantly associated with the following features: family or neighbours with dengue in the past week (AOR: 3.59, 95% CI:2.14-6.00, p<0.001), cutaneous rash (AOR: 3.58, 95% CI:1.77-7.23, p<0.001), increased temperature (AOR: 1.33, 95% CI:1.04-1.70, p = 0.021), leucopenia (white cell count < 4,000/μL) (AOR: 3.44, 95% CI:1.72-6.89, p<0.001) and thrombocytopenia (platelet count <150,000/μL)(AOR: 4.63, 95% CI:2.33-9.21, p<0.001). Dengue infection was negatively associated with runny nose (AOR: 0.47, 95% CI:0.29-0.78, p = 0.003) and arthralgia (AOR: 0.42, 95% CI:0.24-0.75, p = 0.004). Serotyping by nested RT-PCR revealed mostly mono-infections with DENV-2 (n = 64), DENV-1 (n = 32) and DENV-3 (n = 17); 14 co-infections occurred with DENV-1/DENV-2 (n = 13) and DENV-1/DENV-4 (n = 1). Besides dengue, none of the pathogens above were found in patients' serum.

    CONCLUSIONS: Acute undifferentiated febrile infections are a diagnostic challenge for community-based clinicians. Rapid diagnostic tests are increasingly used to diagnose dengue infection but negative tests should be interpreted with caution as they fail to detect a considerable proportion of dengue infection. Certain clinical features and haematological parameters are important in the clinical diagnosis of dengue infection.

    Matched MeSH terms: Dengue Virus/immunology*
Related Terms
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links