scholarly journals Inhibition of dengue virus serotype 2 in Vero cells with [Cu(2,4,5-triphenyl-1H-imidazole)2(H2O)2].Cl2

Author(s):  
Teguh H. Sucipto ◽  
Fahimah Martak

Dengue fever and dengue hemorrhagic fever are transmitted to humans by the Aedes aegypti and Aedes albopictus mosquitoes, with an observed 30-fold increase in global incidence the last 50 years. Despite the tremendous efforts invested anti-dengue virus research, no clinically approved vaccine or antiviral chemotherapeutics are available for humans, and disease treatment is limited to supportive care. Over the years there has been a continuous interest in the chemistry of metal complexes with biological activity, including platinum complexes with antitumor activity and silver complexes with antimicrobial action. Aim of the project was to investigate [Cu(2,4,5-triphenyl-1H- imidazole)2 (H2O)2].Cl2 as antiviral compound that was further tested for inhibitory effect on the replication of dengue virus type 2 (DENV-2) in Vero cell. DENV-2 were infected in Vero cells and replication of virus was measured by Viral ToxGlo with selectivity index value (SI) and determined as the ratio of cytotoxic concentration 50 (CC50) to inhibitory concentration 50 (IC50) for com- pound. The standard curve between concentration of compound (μg/mL) and %viability of cells was analyzed by logarithmic cor- relation regression with regression equation. For infection rates, t-test was used to exam- ine the statistical significances among the concentrations of compound. P<0.05 was considered to be significant. The maximum inhibitory concentration (IC50) of [Cu(2,4,5- triphenyl-1H-imidazole)2 (H2O)2].Cl2 against DENV-2 was 98.62 μg/mL. The cytotoxic concentration (CC50) of compound against Vero cells was 300.36μg/mL. The SI values for [Cu(2,4,5-triphenyl-1H-imidazole)2 (H2O)2].Cl2 1.86. Based on selectivity index values, [Cu(2,4,5-triphenyl-1H-imidazole)2 (H2O)2].Cl2 can inhibit the growth of DENV- 2 and has low toxicity values for Vero cells.

2020 ◽  
Vol 8 (3) ◽  
pp. 183
Author(s):  
Teguh Hari Sucipto ◽  
Aswandi Wibrianto ◽  
Fahimah Martak ◽  
Siti Churrotin ◽  
Ilham Harlan Amarullah ◽  
...  

Dengue virus (DENV) is a significant pathogen emerging worldwide as a cause of infectious disease. DENVs are transmitted to humans through female mosquitoes from Aedes aegypti and Aedes albopictus species. Indonesia is one of the largest countries in the world in dengue endemic regions worldwide. Dengue fever was occurred for the first time as an outbreak in Surabaya and Jakarta in 1968. Many efforts have been made to prevent and treat DENV infections, and clinical trials of a number of vaccines are currently underway. Antiviral testing of DENV is an important alternative for drug characterization and development. Complex compounds are formed as a result of metal and organic complex reactions. Complex compounds can be used as an anti-inflammatory, antimicrobial antifungal, antibacterial, antivirus. The Zn2+ ion can be used as an antiviral candidate. The purpose of this project was investigated Zinc(II)-2,4,5-triphenyl-1H-imidazole antiviral compound to be further tested for inhibitory effect on the replication of DENV-2 in cell culture. DENV replication was measured by antiviral activity assay and cytotoxicity assay. The inhibitory activity of Zinc(II)-2,4,5-triphenyl-1H-imidazole complex compound was determined by Viral ToxGloTM Assay. The cytotoxicity of Zinc(II)-2,4,5-triphenyl-1H-imidazole complex compound was determined by CellTiter96® AQuoeus assay. The inhibitory concentration (IC50) of Zinc(II)-2,4,5-triphenyl- 1H-imidazole against dengue virus type-2 was 34.42 μg/ml. The cytotoxic concentration (CC50) of compound against Vero cell was <100 μg/ml. The results of this study demonstrate the antidengue serotype 2 inhibitory activity of investigated Zinc(II)-2,4,5-triphenyl-1H-imidazole complex and its high toxicity in Vero cells. Further studies are not required before investigated Zinc(II)-2,4,5-triphenylimidazole can be applied in the treatment of DENV-2 infections


2021 ◽  
Vol 2049 (1) ◽  
pp. 012018
Author(s):  
Fitmawati ◽  
Maya Safitri ◽  
S.N. Kholifah ◽  
Emrizal ◽  
Rodesia Mustika Roza

Abstract The new discovery about the potential of Mangifera foetida L. as an antiviral will help conservation efforts in nature while maintaining and increasing its biodiversity value. This study aims to characterize the in vitro potential of three varieties of M. foetida L. against the dengue virus. Dengue virus is infected in Vero cells, viral replication was measured using the Viral ToxGlo Assay method. The selectivity ability of Mangifera foetida L. stem bark extract to inhibit the dengue virus was seen from the Selectivity Index (SI) value. The standard curve between the concentration of the compound (μg/mL) and % cell viability was analyzed by linear regression using Microsoft Excel 2010 software. The results showed that the selectivity index (SI) value of M. foetida L stem bark extract of Limus, Manis and Batu varieties were 7.58, 6.82 and 16.43, respectively. It was concluded that the extract of Macang stem bark of the Limus, Manis and Batu varieties had the potential to be used as an antiviral for dengue.


2020 ◽  
Vol 4 (2) ◽  
pp. 40
Author(s):  
Deya Karsari

This study aims to  analyze   genetic stability of  the gene encoding the envelope protein (E) dengue virus serotype-4 passaged in vero cells, Denv-4 passaged  in vero cells serially then continued with RNA extraction at passage 0, 10, 20, 30, 40 ,50 , and 60, and then continued with two step PCR and amplification, and sequencing then analyze the nucleotide stability with BLAST and MEGA 5 software. The result shows that there are many variable site in nucleotide and amino acid with high mutation rate 57.4% for nucleotide and 71.9% for amino acid ,while the similarity between passages are high ranging from 91% - 98%. The conclusion for this study is Denv-4 after analyzed shows that the gene encoding protein E has many variable site but high in similarity.


PLoS ONE ◽  
2013 ◽  
Vol 8 (1) ◽  
pp. e55407 ◽  
Author(s):  
Juan Wang ◽  
Yanlei Chen ◽  
Na Gao ◽  
Yisong Wang ◽  
Yanping Tian ◽  
...  

2017 ◽  
Vol 6 (6) ◽  
pp. 141
Author(s):  
Teguh Hari Sucipto ◽  
Siti Churrotin ◽  
Harsasi Setyawati Setyawati ◽  
Kris Cahyo Mulyatno ◽  
Ilham Harlan Amarullah ◽  
...  

Dengue virus (DENV) is a significant pathogen emerging worldwide as a cause of infectious disease. Antidengue treatments are urgently required to control the emergence of dengue. DENV is a mosquito-borne disease responsible for acute systemic diseases and serious health conditions. DENVs were distributed in the tropical and sub-tropical areas and transmitted to humans by Aedes agypty and Aedes albopictus. Dengue vaccine or antiviral has not yet been clinically approved for humans, even though there have been great efforts toward this end. Antiviral activity against DENV is an important alternative for the characterization and development of drugs. Metal–organic compounds were reported to exhibit fungicidal, bactericidal, and antiviral activities its inhibitory activity was not significant, at high concentration it was more toxic to replicating cells than to stationary cell monolayers of Vero cells. The aim of this study is to investigate the antiviral effects of Cobalt(II)–Morin complex. This compound was further investigated for its inhibitory effect on the replication of DENV-2 in Vero cells. The replication of DENV was measured by enzyme-linked immunosorbent assay and the value of selectivity index (SI). SI was determined as the ratio of the 50% cytotoxic concentration (CC50) to the 50% inhibitory concentration (IC50). The IC50 value of the Cobalt(II)–Morin complex for DENV-2 was 3.08 µg/ml, and the CC50 value of the complex for Vero cells was 3.36 µg/ml; thus, the SI value was 1.09. The results of this study demonstrate the antidengue serotype 2 inhibitory activity of Cobalt(II)–Morin complex and its high toxicity in Vero cells. Further studies are not required before Co(II)–Morin can be applied in the treatment of DENV-2 infections.


Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1279 ◽  
Author(s):  
Vicky Roa-Linares ◽  
Yaneth Miranda-Brand ◽  
Verónica Tangarife-Castaño ◽  
Rodrigo Ochoa ◽  
Pablo García ◽  
...  

Quinones are secondary metabolites of higher plants associated with many biological activities, including antiviral effects and cytotoxicity. In this study, the anti-herpetic and anti-dengue evaluation of 27 terpenyl-1,4-naphthoquinone (NQ), 1,4-anthraquinone (AQ) and heterocycle-fused quinone (HetQ) derivatives was done in vitro against Human Herpesvirus (HHV) type 1 and 2, and Dengue virus serotype 2 (DENV-2). The cytotoxicity on HeLa and Jurkat tumor cell lines was also tested. Using plaque forming unit assays, cell viability assays and molecular docking, we found that NQ 4 was the best antiviral compound, while AQ 11 was the most active and selective molecule on the tested tumor cells. NQ 4 showed a fair antiviral activity against Herpesviruses (EC50: <0.4 µg/mL, <1.28 µM) and DENV-2 (1.6 µg/mL, 5.1 µM) on pre-infective stages. Additionally, NQ 4 disrupted the viral attachment of HHV-1 to Vero cells (EC50: 0.12 µg/mL, 0.38 µM) with a very high selectivity index (SI = 1728). The in silico analysis predicted that this quinone could bind to the prefusion form of the E glycoprotein of DENV-2. These findings demonstrate that NQ 4 is a potent and highly selective antiviral compound, while suggesting its ability to prevent Herpes and Dengue infections. Additionally, AQ 11 can be considered of interest as a leader for the design of new anticancer agents.


2018 ◽  
Vol 6 (24) ◽  
Author(s):  
Gabriela M. Blohm ◽  
Alberto E. Paniz-Mondolfi ◽  
Marilianna C. Márquez ◽  
Julia C. Loeb ◽  
Carlos Pacheco ◽  
...  

ABSTRACT The complete genome sequence was obtained for a Dengue virus 2 isolate from the urine of an 8-year-old girl who was hospitalized with dengue hemorrhagic fever in 2016 in Venezuela.


2016 ◽  
Vol 91 (5) ◽  
Author(s):  
Usha K. Nivarthi ◽  
Nurgun Kose ◽  
Gopal Sapparapu ◽  
Douglas Widman ◽  
Emily Gallichotte ◽  
...  

ABSTRACT The four dengue virus (DENV) serotypes are mosquito-borne flaviviruses responsible for dengue fever and dengue hemorrhagic fever. People exposed to DENV develop antibodies (Abs) that strongly neutralize the serotype responsible for infection. Historically, infection with DENV serotype 4 (DENV4) has been less common and less studied than infections with the other three serotypes. However, DENV4 has been responsible for recent large and sustained epidemics in Asia and Latin America. The neutralizing antibody responses and the epitopes targeted against DENV4 have not been characterized in human infection. In this study, we mapped and characterized epitopes on DENV4 recognized by neutralizing antibodies in people previously exposed to DENV4 infections or to a live attenuated DENV4 vaccine. To study the fine specificity of DENV4 neutralizing human antibodies, B cells from two people exposed to DENV4 were immortalized and screened to identify DENV-specific clones. Two human monoclonal antibodies (MAbs) that neutralized DENV4 were isolated, and their epitopes were finely mapped using recombinant viruses and alanine scan mutation array techniques. Both antibodies bound to quaternary structure epitopes near the hinge region between envelope protein domain I (EDI) and EDII. In parallel, to characterize the serum neutralizing antibody responses, convalescence-phase serum samples from people previously exposed to primary DENV4 natural infections or a monovalent DENV4 vaccine were analyzed. Natural infection and vaccination also induced serum-neutralizing antibodies that targeted similar epitope domains at the EDI/II hinge region. These studies defined a target of neutralizing antigenic site on DENV4 targeted by human antibodies following natural infection or vaccination. IMPORTANCE The four serotypes of dengue virus are the causative agents of dengue fever and dengue hemorrhagic fever. People exposed to primary DENV infections develop long-term neutralizing antibody responses, but these principally recognize only the infecting serotype. An effective vaccine against dengue should elicit long-lasting protective antibody responses to all four serotypes simultaneously. We and others have defined antigenic sites on the envelope (E) protein of viruses of dengue virus serotypes 1, 2, and 3 targeted by human neutralizing antibodies. The epitopes on DENV4 E protein targeted by the human neutralizing antibodies and the mechanisms of serotype 4 neutralization are poorly understood. Here, we report the properties of human antibodies that neutralize dengue virus serotype 4. People exposed to serotype 4 infections or a live attenuated serotype 4 vaccine developed neutralizing antibodies that bound to similar sites on the viral E protein. These studies have provided a foundation for developing and evaluating DENV4 vaccines.


2017 ◽  
Vol 6 (4) ◽  
pp. 84 ◽  
Author(s):  
Teguh Hari Sucipto ◽  
Siti Churrotin ◽  
Harsasi Setyawati ◽  
Tomohiro Kotaki ◽  
Fahimah Martak ◽  
...  

Infection of dengue virus (DENV) was number of globally significant emerging pathogen. Antiviral dengue therapies ar importantly needed to control emerging dengue. Dengue virus (DENV) is mosquito-borne arboviruses responsible for causing acute systemic diseases and grievous health conditions in humans. To date, there is no clinically approved dengue vaccine or antiviral for humans, even though there have been great efforts towards this end. Copper and copper compounds have more effective in inactivation viruses, likes an influenza virus and human immunodeficiency virus (HIV). Purpose in this project was investigated of Copper(II)chloride Dihydrate antiviral compound were further tested for inhibitory effect on the replication of DENV-2 in cell culture. DENV replication was measures by Enzyme linked Immunosorbent Assay (ELISA) with selectivity index value (SI) was determined as the ratio of cytotoxic concentration 50 (CC50) to inhibitory concentration 50 (IC50) for compound. The maximal inhibitory concentration (IC50) of Copper(II)chloride Dihydrate against dengue virus type-2 was 0.13 μg/ml. The cytotoxic concentration (CC50) of compound against Vero cell was 5.03 μg/ml. The SI values for Copper(II)chloride Dihydrate 38.69. Result of this study suggest that Copper(II)chloride Dihydrate demonstated significant anti-DENV-2 inhibitory activities and not toxic in the Vero cells. Copper mechanisms play an important role in the prevention of copper toxicity, exposure to excessive levels of copper can result in a number of adverse health effects, as a result increased reactive oxygen species and oxidative damage to lipid, DNA, and proteins have been observed in human cell culture models or clinical syndromes of severe copper deficiency and inhibition was attributed to released cupric ions which react with cysteine residues on the surface of the protease.


Author(s):  
Suci Andriani ◽  
Aryati Aryati ◽  
Usman Hadi

The clinical manifestation of dengue virus infection is often not clear, varies widely from mild to severe. Exposure of dengue virus which serotype is different from a previous infection is a risk factor for the severe manifestation of dengue virus infection. Dengue hemorrhagic fever is classified into four degrees of severity based on clinical manifestations and laboratory results. Real-time RT-PCR Dengue can detect dengue virus serotype in early dengue virus infection. The aimed of this study was to prove the correlation between dengue virus serotype and degree of severity in adult patients. This study was a cross-sectional observational design done in February until July 2016. Subjects consisted of 100 dengue virus infection patients. Serum of the patients was examined using Real-time RT-PCR Dengue (Simplexa™ Dengue). It was shown that from 46 patients with DENV-3 serotype was 63%, DENV-2 serotype 17.4%, DENV-1 serotypes 17.4% and mixed infection of DENV-1 and DENV-3 serotype 2.2%. There was not any DENV-4 serotype. Dengue Hemorrhagic Fever (DHF) stage I was 47.8%, DHF stage II was 30.4%, DHF stage III was 10.9% and Dengue Fever was 10.9%. There was not any DHF stage IV. There was not enough evidence that DENV-3 correlated with the degree of severity (p= 0.510). Based on this research, DENV-3 serotype was the dominant serotype prevalent at the Dr. Soetomo Hospital. There was no correlation between viral dengue serotype and severity in dengue adult patients in this study. 


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