Reaction mechanism of the dengue virus serine protease: a QM/MM study

2016 ◽  
Vol 18 (44) ◽  
pp. 30288-30296 ◽  
Author(s):  
M. C. P. Lima ◽  
G. M. Seabra
Keyword(s):  
Reaction Mechanism ◽  
Dengue Virus ◽  
Viral Infection ◽  
Serine Protease ◽  
Dengue Fever ◽  
Causative Agent ◽  
Viral Polyprotein

The dengue virus (DENV) is the causative agent of the viral infection dengue fever. It utilizes the NS2B-NS3pro serine protease to cleave the viral polyprotein into its constituents. We present here a QM/MM to study of the first step (acylation) of the reaction catalyzed by NS2B-NS3pro, using PDDG/PM3 for the QM subsystem, and Amber ff99SB for the MM subsystem.

scholarly journals FEVER AS INDICATOR TO SECONDARY INFECTION IN DENGUE VIRAL INFECTION

2018 ◽  
Vol 7 (1) ◽  
pp. 21
Author(s):  
Soegeng Soegijanto ◽  
Sufiandika Nuryandari ◽  
Siti Churrotin ◽  
Teguh Hari Sucipto
Keyword(s):  
Virus Infection ◽  
Dengue Virus ◽  
Viral Infection ◽  
Dengue Fever ◽  
Clinical Manifestation ◽  
Secondary Infection ◽  
Salmonella Typhi ◽  
Severe Dengue ◽  
Concurrent Infection ◽  
Dengue Virus Infection

Dengue Virus Infections are distributed in tropical and sub-tropical regions and transmitted by the mosquitoes such as Aedes aegypti and Aedes albopictus. Dengue virus can cause dengue fever, dengue hemorrhagic fever and dengue shock syndrome or dengue and severe dengue classified by World Health Organization. Beside it concurrent infection virus salmonella had been found some cases who showed fever more than 7 days. Concurrent infection with two agents can result in an illness having overlapping symptoms creating a diagnostic dilemma for treating physician, such as dengue fever with typhoid fever. The aim of this research is detection of dengue virus and secondary infection with Salmonella typhi in patients suspected dengue virus infection. Detection of dengue virus and Salmonella typhi using immunochromatography test such as NS1, IgG/IgM for dengue virus infection, and IgM/IgG Salmonella and blood culture. The fifty children with dengue virus infection came to Soerya hospital and 17 cases suspected dengue virus infection, five cases showed a positive NS1 on the second day of fever and one case concurrent with clinical manifestation of convulsi on the third days of fever there were five cases only showed positive. It was showed in this study that on the fourth to six day of fever in dengue virus infection accompanied by antibody IgM & IgG dengue. There were 12 cases showed the clinical manifestation of concurrent dengue viral infection and Salmonella, all of them showed a mild clinical manifestation and did not show plasma leakage and shock. In this study we found the length of stay of concurrent Dengue Virus Infection and Salmonella infection is more than 10 days. These patients were also more likely to have co-existing haemodynamic disturbances and bacterial septicaemia which would have required treatment with inotropes and antibiotics. This idea is very important to make update dengue viral management to decrease mortality in outbreak try to gain new prevention method before the occurrence of outbreak.

scholarly journals Computational Analyses of NS3 Serine Protease of Dengue Virus

1970 ◽  
Vol 23 (2) ◽  
pp. 107-113 ◽  
Author(s):  
Dr Jesmin ◽  
Nazlee Sharmin
Keyword(s):  
Dengue Virus ◽  
Serine Protease ◽  
Active Site ◽  
Serine Proteases ◽  
Binding Pocket ◽  
Active Site Pocket ◽  
Promising Target ◽  
Actual Environment ◽  
Viral Polyprotein ◽  
Computational Analyses

Dengue virus (DENV), a mosquito-borne Flavivirus, is an emerging global health threat. A number of studies have already revealed that the non-structural NS3 serine protease is required for the maturation of the viral polyprotein and thus is a promising target for the development of antiviral inhibitors. However, the residues and other structural elements that play a role in the enzyme-mediated maturation process of DENV by NS3 have yet to be definitely assigned. Identification of the binding site and the actual environment around the active site pocket are still open to questions. To elucidate the functions of DENV NS3 and in particular, for a better understanding of the active site pocket of the enzyme, a 3D model of DEN2 NS3 serine protease to locate its key catalytic residues has been proposed. From computational comparative analyses of sequences and structures of related NS3 serine proteases of the Flaviviridae family, the charge distribution and electrostatic potential in and around the active site pocket of DEN2-NS3 serine protease have also been predicted. This proposed model would facilitate future studies for better rationalize the environment of the substrate-binding pocket and thus stimulate more rationally designed structure-function studies aimed at elucidating the role of this enzyme in virus maturation.Keywords: Dengue virus (DENV), Flaviviridae, NS3 serine protease, PolyproteinDOI: http://dx.doi.org/10.3329/bjm.v23i2.872 Bangladesh J Microbiol, Volume 23, Number 2, December 2006, pp 107-113

scholarly journals A short report on Dengue Fever

2017 ◽  
Vol 08 (01) ◽  
pp. 60-61
Author(s):  
Mahwish Fatima ◽  
Subia Jamil
Keyword(s):  
Aedes Aegypti ◽  
Dengue Virus ◽  
Viral Infection ◽  
Dengue Fever ◽  
Aedes Albopictus ◽  
Rna Virus ◽  
Short Report ◽  
Female Mosquito

Dengue fever is a deadly mosquito-borne viral infection. It is caused by the bite of female mosquito by Aedes aegypti and in some cases also by Aedes albopictus, infected with the virus. Dengue virus is RNA virus, which is single-stranded.

scholarly journals Retrospective Seroepidemiology study of dengue virus infection in Taiwan

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ying-Hsuan Lee ◽  
Yu-Chia Hsieh ◽  
Chih-Jung Chen ◽  
Tzou-Yien Lin ◽  
Yhu-Chering Huang
Keyword(s):  
General Population ◽  
Virus Infection ◽  
Dengue Virus ◽  
Dengue Fever ◽  
Health Concern ◽  
Age Group ◽  
Dengue Virus Infection ◽  
Recent Infection ◽  
Seropositive Rate ◽  
Significant Difference

Abstract Background Dengue virus infection has been an important and serious public health concern in Taiwan, where local outbreaks of dengue fever occurred almost every year. To our knowledge, no nationwide investigation has been carried out to determine the actual extent of infection in the general population. Methods A total of 1308 random serum samples were collected from the general population in Taiwan in 2010. The antibody-captured enzyme-linked immunosorbent assays were used to detect DENV-specific IgM and IgG. Demographics data were used for risk analysis. Results The weighted overall seroprevalence was 1.96% for anti-DENV IgM, and 3.4% for anti-DENV IgG, respectively. A significant rise of DENV IgG seropositive rate had been noted since late adulthood stage, from 1.1% at the age group of 50–59 years to 7.6% at the age group of 60–69 years. For people aged over 70 years, the seropositive rate reached 19%. Age, nationality, and regions of residency were associated with the IgG seropositivity. There was no statistically significant difference in seroprevalence of anti-Dengue IgM, indicating recent infection, among univariate predictors we proposed, including gender, age, residency, nationality, and household size. Conclusions Our results indicated that the majority of population in Taiwan born after 1940 is naive to dengue virus and the prevalence of IgG antibody against dengue virus rises with age. Nationality, and regions of residency are associated with the exposure of population to infection by dengue viruses. Further studies are needed to realize the current situation of seroprevalence of dengue fever in Taiwan.

scholarly journals Micafungin Inhibits Dengue Virus Infection through the Disruption of Virus Binding, Entry, and Stability

2021 ◽  
Vol 14 (4) ◽  
pp. 338
Author(s):  
Yen-Chen Chen ◽  
Jeng-Wei Lu ◽  
Chia-Tsui Yeh ◽  
Te-Yu Lin ◽  
Feng-Cheng Liu ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Dengue Fever ◽  
Early Stage ◽  
Quantitative Polymerase Chain Reaction ◽  
Enterovirus 71 ◽  
Denv Infection ◽  
Immunofluorescence Assay ◽  
Dependent Manner ◽  
Virus Binding ◽  
Virus Serotype

Dengue fever is an arbovirus disease caused by infection with the dengue virus (DENV). Half of the world’s population lives under the threat of dengue fever, however, researchers have yet to develop any drugs that are clinically applicable to this infection. Micafungin is a member of the echinocandins family of anti-fungal drugs, capable of blocking the synthesis of β-1,3-D-glucan in the walls of fungal cells. Previous studies have demonstrated the effectiveness of Micafungin against infections of enterovirus 71 (EV71) and chikungunya virus (CHIKV). This is the first study demonstrating the effectiveness of micafungin in inhibiting the cytopathic effects of dengue virus serotype 2 (DENV-2) in a dose-dependent manner. Time-of-addition assays verified the inhibitory effects of micafungin in pre-treated, co-treated, and full-treatment groups. Binding and entry assays also demonstrated the effectiveness of micafungin in the early stage of DENV-2 infection. The virucidal efficacy of micafungin appears to lie in its ability to destroy the virion. Molecular docking assays revealed the binding of micafungin to the envelope protein of DENV-2, thereby revealing the mechanism by which micafungin affects the early stage of DENV infection and the stability of DENV. Two other micafungin analogs, caspofungin and anidulafungin, were also shown to have the antiviral effects on DENV-2. Finally, immunofluorescence assay (IFA) and reverse-transcription quantitative polymerase chain reaction (RT-qPCR) confirmed the broad anti-DENV ability of micafungin against dengue virus serotypes 1, 3, and 4 (DENV-1, DENV-3, and DENV-4). Taken together, these results demonstrate the potential of micafungin and its analogs as candidates for the development of broad-spectrum treatments for DENV infection.

scholarly journals Dengue Virus NS3 Serine Protease

1999 ◽  
Vol 274 (9) ◽  
pp. 5573-5580 ◽  
Author(s):  
H. M. Krishna Murthy ◽  
S. Clum ◽  
R. Padmanabhan
Keyword(s):  
Dengue Virus ◽  
Serine Protease

scholarly journals Diterpenes/Diterpenoids and Their Derivatives as Potential Bioactive Leads against Dengue Virus: A Computational and Network Pharmacology Study

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 6821
Author(s):  
Rasel Ahmed Khan ◽  
Rajib Hossain ◽  
Abolghasem Siyadatpanah ◽  
Khattab Al-Khafaji ◽  
Abul Bashar Ripon Khalipha ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Dengue Fever ◽  
Computational Study ◽  
Viral Proteins ◽  
Network Pharmacology ◽  
Binding Affinities ◽  
Ns1 Protein ◽  
Structural Protein ◽  
E Protein

Dengue fever is a dangerous infectious endemic disease that affects over 100 nations worldwide, from Africa to the Western Pacific, and is caused by the dengue virus, which is transmitted to humans by an insect bite of Aedes aegypti. Millions of citizens have died as a result of dengue fever and dengue hemorrhagic fever across the globe. Envelope (E), serine protease (NS3), RNA-directed RNA polymerase (NS5), and non-structural protein 1 (NS1) are mostly required for cell proliferation and survival. Some of the diterpenoids and their derivatives produced by nature possess anti-dengue viral properties. The goal of the computational study was to scrutinize the effectiveness of diterpenoids and their derivatives against dengue viral proteins through in silico study. Methods: molecular docking was performed to analyze the binding affinity of compounds against four viral proteins: the envelope (E) protein, the NS1 protein, the NS3 protein, and the NS5 protein. Results: among the selected drug candidates, triptolide, stevioside, alepterolic acid, sphaeropsidin A, methyl dodovisate A, andrographolide, caesalacetal, and pyrimethamine have demonstrated moderate to good binding affinities (−8.0 to −9.4 kcal/mol) toward the selected proteins: E protein, NS3, NS5, and NS1 whereas pyrimethamine exerts −7.5, −6.3, −7.8, and −6.6 kcal/mol with viral proteins, respectively. Interestingly, the binding affinities of these lead compounds were better than those of an FDA-approved anti-viral medication (pyrimethamine), which is underused in dengue fever. Conclusion: we can conclude that diterpenoids can be considered as a possible anti-dengue medication option. However, in vivo investigation is recommended to back up the conclusions of this study.

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