scholarly journals Progress in the Identification of Dengue Virus Entry/Fusion Inhibitors

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Carolina De La Guardia ◽  
Ricardo Lleonart

Dengue fever, a reemerging disease, is putting nearly 2.5 billion people at risk worldwide. The number of infections and the geographic extension of dengue fever infection have increased in the past decade. The disease is caused by the dengue virus, a flavivirus that uses mosquitosAedessp. as vectors. The disease has several clinical manifestations, from the mild cold-like illness to the more serious hemorrhagic dengue fever and dengue shock syndrome. Currently, there is no approved drug for the treatment of dengue disease or an effective vaccine to fight the virus. Therefore, the search for antivirals against dengue virus is an active field of research. As new possible receptors and biological pathways of the virus biology are discovered, new strategies are being undertaken to identify possible antiviral molecules. Several groups of researchers have targeted the initial step in the infection as a potential approach to interfere with the virus. The viral entry process is mediated by viral proteins and cellular receptor molecules that end up in the endocytosis of the virion, the fusion of both membranes, and the release of viral RNA in the cytoplasm. This review provides an overview of the targets and progress that has been made in the quest for dengue virus entry inhibitors.

Author(s):  
Henry Puerta-Guardo ◽  
Scott B. Biering ◽  
Eva Harris ◽  
Norma Pavia-Ruz ◽  
Gonzalo Vázquez-Prokopec ◽  
...  

Dengue is the most prevalent emerging mosquito-borne viral disease, affecting more than 40% of the human population worldwide. Many symptomatic dengue virus (DENV) infections result in a relatively benign disease course known as dengue fever (DF). However, a small proportion of patients develop severe clinical manifestations, englobed in two main categories known as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Secondary infection with any of the four dengue virus serotypes (DENV1, -2, -3, and -4) is a risk factor to develop severe forms of dengue disease. DSS is primarily characterized by sudden and abrupt endothelial dysfunction, resulting in vascular leak and organ impairment, which may progress to hypovolemic shock and death. Severe DENV disease (DHF/DSS) is thought to follow a complex relationship between distinct immunopathogenic processes involving host and viral factors, such as the serotype cross-reactive antibody-dependent enhancement (ADE), the activation of T cells and complement pathways, the phenomenon of the cytokine storm, and the newly described viral toxin activity of the nonstructural protein 1 (NS1), which together play critical roles in inducing vascular leak and virus pathogenesis. In this chapter that is divided in two parts, we will outline the recent advances in our understanding of DENV pathogenesis, highlighting key viral-host interactions and discussing how these interactions may contribute to DENV immunopathology and the development of vascular leak, a hallmark of severe dengue. Part I will address the general features of the DENV complex, including the virus structure and genome, epidemiology, and clinical outcomes, followed by an updated review of the literature describing the host innate immune strategies as well as the viral mechanisms acting against and in favor of the DENV replication cycle and infection.


2021 ◽  
Vol 2 (1) ◽  
pp. 33-41
Author(s):  
Saharnauli Janna Verawaty Simorangkir

Abstrak Penyakit demam berdarah merupakan salah satu masalah kesehatan di Kota Medan yang cenderung menimbulkan kekhawatiran masyarakat karena perjalanan penyakitnya cepat dan dapat menyebabkan kematian dalam waktu yang singkat. Penyakit demam berdarah adalah penyakit yang disebabkan oleh virus dengue. Virus ini ditularkan melalui vector nyamuk. Pendekatan pemberantasan demam berdarah yang berwawasan kepedulian masyarakat merupakan salah satu alternatif pendekatan baru dalam rangka pengendalian penyebaran penyakit ini. Tujuan dari kegiatan ini adalah untuk memberikan penjelasan kepada pelajar-pelajar yang diharapkan dapat menjadi agent of change di lingkungannya dalam pemberantasan penyakit DBD ini. Metode kegiatan ini dilaksanakan dalam bentuk penyuluah, tanya jawab dan games. Kegiatan ini dinilai cukup berhasil. Indikator keberhasilannya adalah berdasarkan antusiasme peserta untuk bertanya dan feedback dari peserta yang menyatakan penyuluhan ini dinilai menarik dan bermanfaat. Kesimpulan dari kegiatan ini adalah melalui keilmuan yang dimiliki dapat digunakan untuk membantu memberikan pemahaman mengenai penyakit-penyakit kepada masyarakat, yang pada akhirnya dapat mendorong partisipasi masyarakat dalam pencegahan penularan dan pertambahan kasus-kasus penyakit tertentu di masyarakat Abstract Dengue fever is one of the health problems in Medan City which tends to cause public concern because the disease progresses quickly and can cause death in a short time. Dengue fever is a disease caused by the dengue virus. This virus is transmitted by mosquito vectors. The approach to eradicating dengue fever with a public concern is an alternative to a new approach to control the spread of this disease. The purpose of this activity is to provide explanations to students who are expected to become agents of change in their environment in eradicating this dengue disease. This activity method was carried out in the form of counseling, question and answer and games. This activity was considered quite successful. The success indicator was based on the enthusiasm of the participants to asked questions and feedback from the participants who stated that this counseling was considered interesting and useful. The conclusion of this activity was that through the knowledge that is owned it can be used to help provide an understanding of diseases to the community, which in turn can encourage community participation in preventing the transmission of certain diseases in the community.


2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Nadine A. Dalrymple ◽  
Erich R. Mackow

Dengue viruses cause two severe diseases that alter vascular fluid barrier functions, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). The endothelium is the primary fluid barrier of the vasculature and ultimately the effects of dengue virus infection that cause capillary leakage impact endothelial cell (EC) barrier functions. The ability of dengue virus to infect the endothelium provides a direct means for dengue to alter capillary permeability, permit virus replication, and induce responses that recruit immune cells to the endothelium. Recent studies focused on dengue virus infection of primary ECs have demonstrated that ECs are efficiently infected, rapidly produce viral progeny, and elicit immune enhancing cytokine responses that may contribute to pathogenesis. Furthermore, infected ECs have also been implicated in enhancing viremia and immunopathogenesis within murine dengue disease models. Thus dengue-infected ECs have the potential to directly contribute to immune enhancement, capillary permeability, viremia, and immune targeting of the endothelium. These effects implicate responses of the infected endothelium in dengue pathogenesis and rationalize therapeutic targeting of the endothelium and EC responses as a means of reducing the severity of dengue virus disease.


2017 ◽  
Vol 27 (16) ◽  
pp. 3851-3855 ◽  
Author(s):  
Emilse S. Leal ◽  
M. Gabriela Aucar ◽  
Leopoldo G. Gebhard ◽  
Nestor G. Iglesias ◽  
María J. Pascual ◽  
...  

2015 ◽  
Vol 90 (1) ◽  
pp. 92-102 ◽  
Author(s):  
Xavier Carnec ◽  
Laurent Meertens ◽  
Ophélie Dejarnac ◽  
Manuel Perera-Lecoin ◽  
Mohamed Lamine Hafirassou ◽  
...  

ABSTRACT Dengue virus (DENV) is the etiological agent of the major human arboviral disease. We previously demonstrated that the TIM and TAM families of phosphatidylserine (PtdSer) receptors involved in the phagocytosis of apoptotic cells mediate DENV entry into target cells. We show here that human CD300a, a recently identified phospholipid receptor, also binds directly DENV particles and enhances viral entry. CD300a facilitates infection of the four DENV serotypes, as well as of other mosquito-borne viruses such as West Nile virus and Chikungunya virus. CD300a acts as an attachment factor that enhances DENV internalization through clathrin-mediated endocytosis. CD300a recognizes predominantly phosphatidylethanolamine (PtdEth) and to a lesser extent PtdSer associated with viral particles. Mutation of residues in the IgV domain critical for phospholipid binding abrogate CD300a-mediated enhancement of DENV infection. Finally, we show that CD300a is expressed at the surface of primary macrophages and anti-CD300a polyclonal antibodies partially inhibited DENV infection of these cells. Overall, these data indicate that CD300a is a novel DENV binding receptor that recognizes PtdEth and PtdSer present on virions and enhance infection. IMPORTANCE Dengue disease, caused by dengue virus (DENV), has emerged as the most important mosquito-borne viral disease of humans and is a major global health concern. The molecular bases of DENV-host cell interactions during virus entry are poorly understood, hampering the discovery of new targets for antiviral intervention. We recently discovered that the TIM and TAM proteins, two receptor families involved in the phosphatidylserine (PtdSer)-dependent phagocytic removal of apoptotic cells, interact with DENV particles-associated PtdSer through a mechanism that mimics the recognition of apoptotic cells and mediate DENV infection. In this study, we show that CD300a, a novel identified phospholipid receptor, mediates DENV infection. CD300a-dependent DENV infection relies on the direct recognition of phosphatidylethanolamine and to a lesser extent PtdSer associated with viral particles. This study provides novel insights into the mechanisms that mediate DENV entry and reinforce the concept that DENV uses an apoptotic mimicry strategy for viral entry.


2010 ◽  
Vol 15 (38) ◽  
Author(s):  
K Vainio ◽  
S Noraas ◽  
M Holmberg ◽  
H Fremstad ◽  
M Wahlstrøm ◽  
...  

Between 2008 and 2010, eight cases of viraemic dengue fever in travellers were diagnosed in Norway. They had returned from Eritrea, Thailand and Indonesia. All cases were primary dengue infections, seven non-complicated dengue fever and one dengue shock syndrome with a fatal outcome. Four patients were infected with dengue virus serotype 1, one with type 2 and three with type 3. Two cases from Thailand, the fatal case and the two imported from Eritrea were infected with type 1.


Author(s):  
Richmond Ronald Gomes ◽  

Dengue is a mosquito-borne disease (female mosquitoes of the Aedes genus, principally Aedes aegypti) caused by any one of four closely related dengue viruses. It is endemic in tropical and subtropical continent. World health organization (WHO) currently estimates there may be 50 -100 million dengue infections worldwide every year with over 2.5 billion people at risk of dengue. Symptomatic dengue virus infection may manifests as undifferentiated fever, classical dengue fever (with or without unusual hemorrhages), and dengue hemorrhagic fever (with or without shock). Isolated organopathy or expanded dengue syndrome (EDS) was coined by WHO in the year 2012 to describe cases, which do not fall into either dengue shock syndrome or dengue hemorrhagic fever. The atypical manifestations noted in expanded dengue are multisystemic and multifaceted with organ involvement, such as liver, brain, heart, kidney, central/peripheral nervous system, gastrointestinal tract, lympho reticular system. Dengue virus has long been considered as a non-neurotropic virus, as animal studies have shown that virus does not cross blood brain barrier. Hyponatremia may be found in association with dengue fever and is thought to be caused by peripheral fluid extravasation and resulting intravascular hypovolaemia. But hyponatremia due to syndrome of inappropriate secretion of anti-diuretic hormone (SIADH) in Dengue fever is rare. We report a 40 years old male who was diagnosed as Dengue fever (Dengue Ns1Ag positive) with thrombocytopenia and hyponatremia. He was admitted and further investigations revealed SIADH. He responded well to cautious sodium replacement and addition of tolvaptan. He recovered completely and was discharged after one week. Thus, all clinicians should keep in mind the possibility of SIADH as a part of expanded dengue syndrome.


2020 ◽  
Vol 2 (1) ◽  
pp. 57
Author(s):  
Muhammad Luthfi Adnan

Abstract— Dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS) caused by the DENV virus are among the global problems regarding mosquito-borne viral infections. The DENV virus is transmitted through Aedes aegypti causing clinical manifestations that can cause critical illness for patients. The need for effective antiviral therapy is needed to treat DENV virus infections. 1-Deoxynojirimycin (DNJ), one of the many imino sugars found in mulberry leaves and several strains of bacteria, has potential as an antiviral against DENV virus infection. The antiviral activity of DNJ works as an inhibitor of the α-glucosidase enzyme which is important in virus secretion so that it affects the infection rate. DNJ also has the effect of boosting the immune system to initiate an immune response to a viral infection. Further research is needed to develop DNJ as an effective antiviral DENV in the future. Keywords: antiviral, dengue, iminosugar, therapy Abstrak— Dengue fever (DF), dengue hemorraghic fever (DHF), dan dengue shock syndrome (DSS) yang disebabkan oleh virus DENV merupakan salah satu permasalahan global mengenai infeksi virus. Virus DENV ditularkan melalui Aedes aegypti menyebabkan manifestasi klinis yang dapat menimbulkan kesakiatn kritis bagi pasien. kebutuhan terapi antiviral yang efektif diperlukan untuk mengobati infeksi virus DENV. 1-Deoxynojirimycin (DNJ), salah satu iminosugar yang banyak terdapat pada daun mulberry dan beberapa strain bakteri, memiliki potensi sebagai antiviral terhadap infeksi virus DENV. Aktivitas antiviral DNJ bekerja sebagai penghambat enzim α-glukosidase yang penting dalam sekresi virus sehingga mempengaruhi tingkat infeksi. DNJ juga memiliki efek meningkatkan sistem imun untuk menginisiasi respon imun terhadap infeksi virus. Penelitian lebih lanjut diperlukan untuk mengembangkan DNJ sebagai antiviral DENV yang efektif di masa depan. Kata kunci: antiviral, dengue, iminosugar, therapy


1970 ◽  
Vol 7 (5) ◽  
pp. 74-79
Author(s):  
Sushma Muchukota ◽  
Bhoomika L ◽  
Dinesh M C ◽  
Vinutha N Yadav ◽  
Kavana. C ◽  
...  

Background:  Dengue is an Infectious viral disease caused by the dengue virus. Dengue fever is caused by one of four types of dengue virus. It is transmitted by “Aedes aegypti mosquito”. Symptoms include Fever, Arthralgia, Myalgia and Headache etc.,. Dengue is mosquito-borne viral illness. Fluid and electrolyte losses, dengue shock syndrome, residual brain damage, Febrile convulsions, Low platelet count, Significant bleeding, Liver damage are some of the complications of dengue fever Aim The present hospital study aims to illustrate the frequency, distribution and case fatality of dengue fever based on the variables such as age, sex and impact of clinical pharmacist mediated patient counseling. Objectives: To evaluate the perspectives on assessment of prevalence of the dengue fever and the impact of clinical pharmacist mediated in patient counseling. To estimate the prevalence of dengue fever, educate and create awareness about dengue fever and prevent further complications. Methodology:  A prospective Observational study was carried out among 150 patients for a period of 4 months from June 2019 to September 2019 in ESI hospital Indiranagar, Bangalore. Results: Dengue fever is mostly seen among the age groups between 15-55 yrs. An excess of males were found among reported dengue cases than females 54.6 % were males and 45.3% were females. High proportion of cases were reported in adult age groups (25-35 years) in both males and females, Out of 150 cases Dengue fever 89.3% , Dengue hemorrhagic fever is 7.3% and Dengue shock syndrome 3.33%  is  fatality rate and the outcome of dengue fever is  94.66% survival rate and 5.3% death rate. Conclusion: The patients with Dengue fever 89.3% and other types are DHF, DSS 7.3% and 3.3% out of them patients with thrombocytopenia is 64.66% and the platelet transfusion done in 65 patients (43.33%) out of them 142 patients (94.6%) are survived and the death rate is 5.3% the early identification of complications might have increased the survival rate and decreases the mortality in Dengue fever patients.  


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