Hasil Pencarian  ::  Simpan CSV :: Kembali

"[ABSTRAKKasus Demam Berdarah Dengue (DBD) dan demam dengue (DD) dilaporkan meningkat di seluruh dunia setiap tahunnya, terutama di negara Asia Tenggara termasuk Indonesia Gambaran klinis dari DBD/DD adalah demam, sakit kepala, nyeri otot dan sendi, ruam kulit yang mirip dengan campak, dan hasil lab menunjukkan penurunan jumlah trombosit. Hingga saat ini belum ada antiviral khusus untuk DBD. Penelitian ini bertujuan untuk mengevaluasi pengaruh virgin coconut oil (VCO) terhadap replikasi virus dengue (DENV). Penelitian ini merupakan penelitian eksperimental yang dilakukan di Laboratorium Mikrobiologi, Departemen Mikrobiologi, Fakultas Kedokteran Universitas Indonesia. Data yang diperoleh ini berasal dari hasil eksperimen yang dilakukan dengan 6 pengulangan untuk setiap perlakuan yaitu pemberian VCO 5%, 1%, 0,5% dan 0,1%, kontrol negatif dan Dimethyl Sulfoxide (DMSO).Penghambatan replikasi DENV dilihat dengan menghitung titer virus setelah perlakuan VCO. Titer virus dihitung dengan menggunakan metode focus assay. Hasil penelitian menunjukkan bahwa IC50 dari VCO adalah kuat, sementara CC50 VCO adalah moderat. Hal ini menunjukkan bahwa secara signifikan VCO menghambat replikasi DENV dengan kisaran cukup aman untuk digunakan pada sel dalam dosis terbatas. Penelitian lebih lanjut perlu dilakukan untuk mengevaluasi efek VCO pada replikasi DENV in vivo, sehingga dapat ditemukan kandidat anti DENV di masa mendatang.

---

ABSTRACTCases of the Dengue Hemorrhagic Fever (DHF)/Dengue Fever (DF) were reported increasing worldwide annually, especially in South Asia counties including Indonesia The clinical features of DF/DHF are fever, headache, muscle and joint pains, a characteristic skin rash that is similar to measles, which lead to thrombocytopenia as a lab result. Until now, specific antiviral for dengue virus (DENV) is not available yet.The objective of this research was to evaluate the effect of virgin coconut oil (VCO) to the DENV replication. This research was experimental study and was conducted at Microbiology laboratory, Department of Microbiology, Faculty of Medicine University of Indonesia. The data that was obtained for this study came from the experimental studied with 6 repeated experiments for each treatment of various concentartion of 5%, 1%, 0.5% and 0.1% as well as negative control and Dimethyl Sulfoxide (DMSO). Inhibition of DENV replication was determined by calculating of DENV titer after treated with VCO. The focus assay was used to calculate the DENV titer. The result showed that IC50 and CC50 of VCO was strong and moderate respectively. VCO was significantly inhibited the replication of DENV with adequate safe range to use for cells within limited dosages. Therefore, we concluded that VCO can be a candidate antiviral for DENV. Next study is needed to evaluate the effect of VCO in vivo, therefore we will find an antiviral of DENV virus in future.;Cases of the Dengue Hemorrhagic Fever (DHF)/Dengue Fever (DF) were reported increasing worldwide annually, especially in South Asia counties including Indonesia The clinical features of DF/DHF are fever, headache, muscle and joint pains, a characteristic skin rash that is similar to measles, which lead to thrombocytopenia as a lab result. Until now, specific antiviral for dengue virus (DENV) is not available yet.The objective of this research was to evaluate the effect of virgin coconut oil (VCO) to the DENV replication. This research was experimental study and was conducted at Microbiology laboratory, Department of Microbiology, Faculty of Medicine University of Indonesia. The data that was obtained for this study came from the experimental studied with 6 repeated experiments for each treatment of various concentartion of 5%, 1%, 0.5% and 0.1% as well as negative control and Dimethyl Sulfoxide (DMSO).Inhibition of DENV replication was determined by calculating of DENV titer after treated with VCO. The focus assay was used to calculate the DENV titer. The result showed that IC50 and CC50 of VCO was strong and moderate respectively. VCO was significantly inhibited the replication of DENV with adequate safe range to use for cells within limited dosages. Therefore, we concluded that VCO can be a candidate antiviral for DENV. Next study is needed to evaluate the effect of VCO in vivo, therefore we will find an antiviral of DENV virus in future., Cases of the Dengue Hemorrhagic Fever (DHF)/Dengue Fever (DF) were reported increasing worldwide annually, especially in South Asia counties including Indonesia The clinical features of DF/DHF are fever, headache, muscle and joint pains, a characteristic skin rash that is similar to measles, which lead to thrombocytopenia as a lab result. Until now, specific antiviral for dengue virus (DENV) is not available yet.The objective of this research was to evaluate the effect of virgin coconut oil (VCO) to the DENV replication. This research was experimental study and was conducted at Microbiology laboratory, Department of Microbiology, Faculty of Medicine University of Indonesia. The data that was obtained for this study came from the experimental studied with 6 repeated experiments for each treatment of various concentartion of 5%, 1%, 0.5% and 0.1% as well as negative control and Dimethyl Sulfoxide (DMSO).Inhibition of DENV replication was determined by calculating of DENV titer after treated with VCO. The focus assay was used to calculate the DENV titer. The result showed that IC50 and CC50 of VCO was strong and moderate respectively. VCO was significantly inhibited the replication of DENV with adequate safe range to use for cells within limited dosages. Therefore, we concluded that VCO can be a candidate antiviral for DENV. Next study is needed to evaluate the effect of VCO in vivo, therefore we will find an antiviral of DENV virus in future.]"

"[ABSTRAKDemam berdarah dengue (DBD) adalah penyakit paling umum di negara-negara tropis dan sub-tropis dan ditransmisikan melalui gigitan nyamuk. Namun hingga saat ini, belum ada pengobatan yang spesifik ataupun vaksin untuk DBD. Penelitian ini bertujuan untuk mengevaluasi pengaruh Ribavirin pada replikasi virus dengue (DENV). Penelitian ini merupakan penelitian eksperimental in Vitro yang dilaksanakan di Laboratorium Departemen Mikrobiologi. Kami menggunakan sel Vero dan DENV serotype 1 koleksi Departemen Mikrobiologi. DENV, yang kemudian dipaparkan dengan berbagai konsentrasi Ribavirin dengan 6 kali pengulangan. Sebagai pembanding, kami menggunakan DENV yang dipaparkan dengan pelarut yaitu dimetil sulfoksida (DMSO), sedangkan DENV yang tidak dipaparkan dengan ribavirin atau pelarut digunakan sebagain control negative. Uji fokus digunakan untuk menentukan persentasi inhibisi dari replikasi DENV. Untuk menentukan efek sitotoksik dari ribavirin, kami menggunakan MTS assay (3-(4,5-dimethylthiazol-2-yl)-5-(3 arboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium). Ribavirin dengan konsentrasi 5μg/mL, menghambat replikasi virus sebesar 75% jika dibandingkan dengan DMSO. Pada konsentrasi 1 μg/mL, 0.5 μg/mL, dan 0.1μg/mL, ribavirin menghambat replikasi virus masing-masing sebesar 64%, 46%, dan 50% dan secara statistk menunjukkan perbedaan bermakna. Dari data yang didapat dalam penelitian ini, half inhibitory concentration (IC50) adalah 0.25 μg/mL. Hasil uji MTS menunjukkan bahwa half cytotoxic concentration (CC50) adalah 106.83 μg/mL sehingga ribavirin termasuk dalam katagori tidak toksik. Dari penelitian ini dapat disimpulkan bahwa, ribavirin memiliki inhibisi yang kuat terhadap replikasi terhadap replikasi DENV dan memiliki sitotoksisitas rendah terhadap sel-sel

---

ABSTRACTDengue hemorrhagic fever (DHF) is the most common disease in tropical and sub-tropical countries and is transmitted by mosquito bite. Hitherto, there is still no specific treatment or vaccine for DHF. This study aimed to evaluate the effect of ribavirin to the replication of dengue virus (DENV). This study was an in vitro experimental study that was conducted in Microbiology Department Laboratory.We used vero cells and DENV serotype 1 from the collection of Microbiology Department. DENV was exposed with different concentrations of ribavirin with 6 times of repetition. As a comparison, we used DENV that was exposed to diluent which is dimethyl sulfoxide (DMSO), while DENV that was no exposed to any ribavirin or diluent was used as control negative. Focus assay was used to determine percentage of inhibition of the DENV replication. To determine cytotoxicity effect of ribavirin, we used MTS assay (3-(4,5 dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4sulfophenyl)-2H-tetrazolium). Ribavirin with the concentration of 5μg/mL inhibited virus replication by 75% compared to DMSO. On concetration 1 μg/mL, 0.5 μg/mL, dan 0.1μg/mL, ribavirin inhibited virus replication by 64%, 46%, dan 50%, respectively and statiscally showed significant difference. From the data obtained in this study, the half inhibitory concentration (IC50) was 0.25 μg/mL. The result from MTS assay showed that half cytotoxic concentration (CC50) was 106.83 μg/mL, therefore ribavirin was categorized as non-toxic. In conclusion, ribavirin has a strong inhibition towards the replication of DENV and has a low cytotoxicity to healthy cells., Dengue hemorrhagic fever (DHF) is the most common disease in tropical and sub-tropical countries and is transmitted by mosquito bite. Hitherto, there is still no specific treatment or vaccine for DHF. This study aimed to evaluate the effect of ribavirin to the replication of dengue virus (DENV). This study was an in vitro experimental study that was conducted in Microbiology Department Laboratory.We used vero cells and DENV serotype 1 from the collection of Microbiology Department. DENV was exposed with different concentrations of ribavirin with 6 times of repetition. As a comparison, we used DENV that was exposed to diluent which is dimethyl sulfoxide (DMSO), while DENV that was no exposed to any ribavirin or diluent was used as control negative. Focus assay was used to determine percentage of inhibition of the DENV replication. To determine cytotoxicity effect of ribavirin, we used MTS assay (3-(4,5 dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4sulfophenyl)-2H-tetrazolium). Ribavirin with the concentration of 5μg/mL inhibited virus replication by 75% compared to DMSO. On concetration 1 μg/mL, 0.5 μg/mL, dan 0.1μg/mL, ribavirin inhibited virus replication by 64%, 46%, dan 50%, respectively and statiscally showed significant difference. From the data obtained in this study, the half inhibitory concentration (IC50) was 0.25 μg/mL. The result from MTS assay showed thathalf cytotoxic concentration (CC50) was 106.83 μg/mL, therefore ribavirin was categorized as non-toxic. In conclusion, ribavirin has a strong inhibition towards the replication of DENV and has a low cytotoxicity to healthy cells.]"

"[Demam berdarah dengue adalah penyakit yang dikenal di dunia dan disebabkanoleh infeksi virus dengue (DENV). Meskipun prevalensi penyakit ini cukuptinggi, pengobatan infeksi dengue masih terbatas pada pengobatan suportif.Cyclosporine A telah banyak digunakan sebagai pengobatan infeksi Hepatitis C.Virus hepatitis C dan DENV adalah virus RNA dari genus yang sama, yakniflavivirius. Hingga saat ini, masih belum ada pengobatan untuk infeksi DENV,oleh karena itu kami melakukan penelitian untuk mengetahui efektivitasCyclosporine A. Cyclosporine A digunakan sebagai antiviral infeksi DENV.Dalam penelitian ini kami menggunakan DENV serotipe 1 dan Vero Cell untukpercobaan antivirus in vitro. Kami melakukan pengenceran Cyclosporine Amenggunakan Dymethil sulfoxide (DMSO). Kami memaparkan DENV yangdiinfeksikan kepada sel Vero dengan empat konsentrasi aman dari CyclosporineA, yaitu 5 ug/ml, 1 ug/ml, 0,5 ug/ml, dan 0,1 ug/ml, dan DMSO sebagai kontroldari percobaan kami karena fungsinya yang sebagai materi pelarut dariCyclosporine A. Setelah itu, diinkubasikan selama 3 hari untuk mengetahui efekCyclosporine A terhadap replikasi DENV. Setelah masa inkubasi selesai, kamimemeriksa viabilitas sel Vero dengan menggunakan MTS Assay untukmengetahui efek sitotoksik dari Cyclosporine A. Kami memperoleh hasil IC50 dariFocus Assay dan CC50 dari MTS Assay. Kami juga menentukan indeksselektivitas penelitian yang merupakan perbandingan nilai IC50 dan CC50. Daripenelitian ini, Cyclosporine A telah terbukti memiliki aktivitas antivirus terhadapDENV dengan nilai IC50 sebesar 0,4 ug/ml dan CC50 sebesar 68,47 ug/ml.Sedangkan nilai indeks selektivitas adalah 171. Hal tersebut diatas menunjukanbahwa Cyclosporine A merupakan kandidat antiviral terhadap DENV dimasamendatang., Dengue hemorrhagic fever is world-known disease caused by the infection ofDENV. Despite the high prevalence of this disease, the treatment of dengueinfection is still limited to the supportive treatment. Cyclosporine A has beenwidely used as the treatment of Hepatitis C infection. Hepatitis C virus and DENVare RNA virus from the same genus, flavivirius genus. Up until now, there is stillno absolute treatment for DENV infection, thus we conduct this research to checkthe possibility of Cyclosporine A as the treatment of DENV infection. In thisstudy we used DENV Serotype 1 and Vero Cell for antiviral invitro experiment.We then diluted the Cyclosporine A using Dymethil Sulfoxide (DMSO). Wetreated the cells with four different safe concentrations of Cyclosporine A (5μg/ml, 1 μg/ml, 0.5 μg/ml, and 0.1 μg/ml) and DMSO as the negative control toour study because it functioned as the dilution material of Cyclosporine A. Afterthat, we incubated it for 3 days. Once the incubation period finished, we checkedusing Cell Viability Assay and Focus assay. We obtained the result of IC50 fromthe Focus Assay and we obtained the result of CC50 from Cell Viability Assay.We also determined the selectivity index of the study. From this study,Cyclosporin A has proven to have antiviral activity against DENV. The IC50 is 0.4μg/ml, CC50 is 68.47 μg/ml, and selectivity index is 171.]"

"Tingginya insiden infeksi demam berdarah yang terjadi dan tidak adanya vaksin efektif menyebabkan banyak peneliti mencoba ekstrak tumbuhan sebagai pengobatan alternatif pada virus Dengue (DENV). Curcumin merupakan salah satu ekstrak tumbuhan yang telah dibuktikan memiliki efek antiviral. Penelitian ini bertujuan untuk mengetahui apakah curcumin memiliki efek antiviral pada virus dengue. Oleh karena itu dilakukan tes untuk mengetahui persen hambatan curcumin pada replikasi DENV dan efek cytotoxic curcumin pada sel mamalia. Penelitian ini merupakan penelitian eksperimental yang dilakukan di Departemen Mikrobiologi FKUI. Pada penelitian ini terdapat enam kelompok yaitu perlakuan oleh curcumin dengan empat konsentrasi yang berbeda kontrol negatif dan juga Dimethil Sulfoxide (DMSO). Data yang didapatkan dari eksperimen ini akan dianalisis dengan metode T-test. Dari hasil penelitian terlihat bahwa curcumin terbukti dapat menghambat replikasi virus dengue. Pemberian dosis yang lebih tinggi dapat menghambat 100% replikasi virus. Pada saat konsentrasi curcumin diturunkan, maka penghambatan replikasi DENV secara dratis menurun. Dari data tersebut IC50 dari curcumin diperoleh yaitu kurang dari 0.1 µg/ml. Hasil data menunjukkan bahwa efek cytotoxic curcumin pada sel sangat signifikan pada kosentrasi yang tinggi. Pada konsentrasi yang lebih rendah, viabilitas sel terhitung lebih tinggi. Dari data tersebut dapat dihitung nilai CC50 yaitu 3,46 µg/ml. Dengan membandingkan nilai CC50 dan IC50 dari curcumin, didapatkan nilai selectivity index yaitu lebih dari 34. Dari penelitian ini dapat disimpulkan bahwa curcumin dapat digunakan sebagai antiviral virus dengue di masa mendatang.

---

The high incidence of dengue virus infection and also the absence of effective vaccine cause researchers to look up to use the natural extract as the alternative remedy against the dengue virus (DENV). Curcumin is one of the natural extracts that has already proven to have antiviral effect. The objective of this study experiment aimed to see whether curcumin can be used as the antiviral against dengue virus. Several experiments were conducted to obtain the percentage of inhibition of DENV replication and also to determine the cytotoxic effect of curcumin to mammalian cells. This study was an experimental study that had been conducted at Microbiology Departement of Faculty Medicine of Universitas Indonesia. In this experiment, there were six treatment groups such as four different concentrations of curcumin, negative control and Dimethyl sulfoxide (DMSO). The data from this study were analyzed using T-test method. From this study, the curcumin had been proven to successfully inhibit the replication of dengue virus. The treatment with higher dose of curcumin could totally inhibit the replication of DENV. When we gave less dose of curcumin, the percentage inhibition dropped significantly. This showed that inhibition by curcumin was in dose-dependent manner. Furthermore, from these data we determined the IC50 of curcumin which was less than 0.1 µg/ml. The CC50 of curcumin was 3,46µg/ml. By comparing the result of CC50 and IC50, we found the selectivity index value was more than 34. From this study, it can be concluded that Curcumin can be used as antiviral against dengue virus in the future."

"Latar belakang: Infeksi virus dengue masih menjadi masalah di negara tropis seperti Indonesia. Infeksi virus dengue menyebabkan mortalitas dan morbiditas yang tinggi. Belum ada obat ataupun vaksin yang telah disetujui penggunaannya dan tersedia di dunia untuk penyakit infeksi dengue. Pencegahan infeksi dengue masih terbatas pada pengendalian vektor nyamuk Aedes aegypti. Keempat serotipe virus dengue beredar di Indonesia. Dua genotipe dari virus dengue tipe 1 (DENV-1) yaitu genotipe I dan IV lebih dominan bersirkulasi di Indonesia. Pada tahun 2012, kami mengembangkan kandidat vaksin DNA DENV-1 pUMVC RDS 59/09. Tujuan penelitian ini untuk mengetahui kadar antibodi anti-membran dan envelop DENV-1 yang dihasilkan mencit ddY setelah imunisasi sebanyak tiga kali dengan pUMVC RDS 59/09 dan untuk mengetahui kemampuan antibodi tersebut dalam menetralkan beberapa genotipe DENV-1 yang diisolasi di Indonesia. Metode: Penelitian eksperimental ini dimulai dari perbanyakan pUMVC RDS 59/09 di sel E.coli untuk mendapatkan konsentrasi yang tinggi. Imunisasi dilakukan pada 12 mencit strain ddY dengan pUMVC RDS 59/09 25 μg/100 μl menggunakan needle-free injector, sebanyak tiga kali dengan interval waktu 3 minggu. Sebanyak 12 mencit disediakan sebagai kontrol yang tidak diimunisasi. Antibodi anti-membran dan envelop DENV-1 pada masing-masing serum mencit diperiksa dengan ELISA dan dibaca pada panjang gelombang 450 nm. Berikutnya, pooled serum mencit pasca imunisasi ke 3, digunakan untuk netralisasi 13 isolat DENV-1 dengan metode focus reduction neutralization test (FRNT). Fokus yang didapatkan dari FRNT diwarnai dengan tehnik imunoperoksidase dan dihitung secara manual. Hasil: Rerata nilai OD ELISA antibodi anti-membran dan envelop DENV-1 dari serum mencit kelompok imunisasi yang diambil sebelum imunisasi, pasca imunisasi 1, pasca imunisasi 2 dan pasca imunisasi 3 adalah 0,329;0,843;1,524 dan 1,598, secara berurutan. Terdapat peningkatan nilai OD ELISA antibodi anti-membran dan envelop DENV-1 dari pooled serum mencit kelompok imunisasi pasca imunisasi pertama, kedua dan ketiga dibandingkan dengan baseline. Titer FRNT antibodi anti-membran dan envelop DENV-1 dari pooled serum mencit pasca imunisasi 3 dan pooled serum mencit kontrol terhadap strain DV-1 RDS 59/09 adalah 1/320 dan < 1/10. Titer FRNT 13 isolat DENV-1 oleh antibodi anti-membran dan envelop DENV-1 dari pooled serum mencit pasca imunisasi 3 berkisar dari 1/320 sampai lebih dari 1/1280. Kesimpulan: Variasi genotipe DENV-1 tidak menyebabkan perbedaan titer antibodi netralisasi yang bermakna (p = 0,222), sehingga dapat diuraikan bahwa antibodi anti-membran dan envelop DENV-1 dapat menetralkan 13 isolat DENV-1 Indonesia yang diuji.

---

Introduction: Dengue virus infection is still a burden in tropical country such as Indonesia. Dengue virus infection causes high mortality and morbidity. No drugs or vaccines are approved and available in the world for this disease. Dengue prevention is still limited to vector control. Four dengue serotypes are circulated in Indonesia. Two genotypes of Dengue virus type 1 (DENV-1), namely genotypes I and IV are found predominantly in Indonesia. Previously in 2012, we constructed pUMVC RDS 59/09, the DENV-1 DNA vaccine candidate. The objective of this study is to assess antibody level produced in ddY strain mice after three times immunization with pUMVC RDS 59/09 and to assess the antibody ability to neutralize genotypes of DENV-1 isolated in Indonesia.

Methods: This experimental study was started with propagation of pUMVC RDS 59/09 in E. coli cells to produce high concentration of the DNA. Immunization was carried out with 25 μg/ 100 μl pUMVC RDS 59/09 by needle-free injector, three times in 3 weeks interval. Twelve mice were provided for control without immunization. Anti-DENV-1 membrane and envelope antibody of individual sera were examined by ELISA and absorbance value was measured by ELISA reader in 450 nm wave length. Further, pooled sera of 3rd immunization were used to neutralize 13 DENV-1 isolates by focus reduction neutralization test (FRNT) method. The focus obtained in FRNT was stained by immune-peroxides technique and counted manually.

Results: ELISA OD value mean of anti-DENV-1 membrane and envelope antibody in individual ddY mice sera of immunized group before immunization, post first immunization, after second immunization and post third immunization were 0.329; 0.843; 1.524 and 1.598, respectively. An increase in ELISA OD value of anti-DENV-1 membrane and envelope antibody in ddY mice pooled sera of immunized group after first, second and third immunization compared to baseline was observed. FRNT titre of anti-DENV-1 membrane and envelope antibody from third immunization pooled sera compared to control mice pooled sera in RDS 59/09 isolate neutralization was 1/320 compared to < 1/10. Neutralization titre of 13 DENV-1 isolates by anti-DENV-1 membrane and envelope antibody from third immunization pooled sera ranged from 1/320 to more than 1/1280.

Conclussions: DENV-1 genotype variation did not lead to significant neutralization antibody titre difference (p = 0,222), so it can be explained that anti-DENV-1 membrane and envelope antibody was able to neutralize 13 strains of Indonesia DENV-1 isolates examined."

"[Infeksi dengue (DENV) merupakan salah satu masalah global yang masih dialamihingga saat ini. Diperkirakan 50 hingga 100 juta orang di dunia positif mengalamiinfeksi dengue.Hingga saat ini, tatalaksana infeksi dengue hanyalah berupa terapisuportif dan belum ditemukan pengobatan dan vaksin dengue. SwieteniaMahagoni sudah dikenal dan digunakan sejak dahulu sebagai tanaman obat.Kandungan flavonoid pada tanaman ini diperkirakan memiliki efek antiviral.Untuk itu penelitian ini dilakukan untuk melihat potensi antiviral terhadap DENVdari ekstrak S. Mahagoni. Pada penelitian ini digunakan beberapa konsentrasiyakni 640 μg/mL, 320 μg/mL, 160 μg/mL, 80 μg/mL, 40 μg/mL, 20 μg/mL, 10μg/mL dan kontrol negatif adalah DMSO. Untuk menentukan hambataninfektivitas dapat digunakan metode Focus Assay sehingga dapat diperoleh nilaiInhibitory Concentration (IC50). Selain itu, untuk dilihat viabilitas sel denganmetode MTT assay sehingga diperoleh nilai Cytotoxic Concentration (CC50).Selain itu ditentukan juga nilai indeks selektivitas yang diperoleh dariperbandingan CC50 dan IC50. Berdasarkan hasil IC50, CC50 dan SI yakni 68,97μg/mL, 434,46 μg/mL dan 6,29, dapat dikatakan bahwa S. Mahagoni memilikiefek antiviral sehingga dapat digunakan sebagai antiviral dengue dimasamendatang.;Dengue infection (DENV) still becomes as global burden. It is estimated 50 to100 million people are positively infected by DENV. The recent management ofthis disease has not been found yet, with the lack finding of medicine and vaccine,the main management takes on supportive care. Swietenia mahagoni has beenused as the herbal medicine since long time ago. The flavonoid extract on thatplant is believed to have antiviral effect. This experiment was conducted toevaluate the antiviral DENV potential of S. mahagoni extract. In this experiment,the concentration was made on various concentration, from 640 μg/ml, 320μg/mL, 160 μg/mL, 80 μg/mL, 40 μg/mL, 20 μg/mL, 10 μg/mL, and DMSO asnegative control. Focus assay was used to determine the infectivity inhibitionwhich results of IC50 (inhibitory concentration), and MTT Assay was used todetermine the cell viability which results of CC50 (cytotoxic concentration).Selectivity index was also resulted by divided the value of CC50 with IC50. Theresults of IC50, CC50, and SI of S. mahagoni was 68,97 μg/mL, 433,46 μg/ml, and6,29 μg/ml respectively, S. Mahagoni has antiviral effect and could be consider tobe used as antiviral to DENV in the future, Dengue infection (DENV) still becomes as global burden. It is estimated 50 to100 million people are positively infected by DENV. The recent management ofthis disease has not been found yet, with the lack finding of medicine and vaccine,the main management takes on supportive care. Swietenia mahagoni has beenused as the herbal medicine since long time ago. The flavonoid extract on thatplant is believed to have antiviral effect. This experiment was conducted toevaluate the antiviral DENV potential of S. mahagoni extract. In this experiment,the concentration was made on various concentration, from 640 μg/ml, 320μg/mL, 160 μg/mL, 80 μg/mL, 40 μg/mL, 20 μg/mL, 10 μg/mL, and DMSO asnegative control. Focus assay was used to determine the infectivity inhibitionwhich results of IC50 (inhibitory concentration), and MTT Assay was used todetermine the cell viability which results of CC50 (cytotoxic concentration).Selectivity index was also resulted by divided the value of CC50 with IC50. Theresults of IC50, CC50, and SI of S. mahagoni was 68,97 μg/mL, 433,46 μg/ml, and6,29 μg/ml respectively, S. Mahagoni has antiviral effect and could be consider tobe used as antiviral to DENV in the future]"

"Pendahuluan: Kasus Demam Berdarah Dengue (DBD) di Indonesia pada tahun 2017 mencapai 68.407 kasus dengan provinsi dengan jumlah kasus Dengue terbanyak adalah Provinsi Jawa Barat. Penyebaran penyakit DBD di Indonesia semakin meluas dan umumnya dapat ditularkan kepada anak-anak berusia kurang dari 15 tahun. Namun, pengobatan yang direkomendasikan oleh WHO untuk demam berdarah hanya bersifat simptomatik. Padahal, dengan adanya antivirus Dengue, viral load di dalam tubuh akan cepat berkurang dan mengurangi risiko keparahan penyakit dan penyebaran penyakit. Tujuan penelitian ini adalah untuk mengetahui potensi kuersetin sebagai antivirus Dengue dengan melihat pengaruh pemberian kuersetin pada stadium pasca infeksi dan pra infeksi secara in vitro serta menganalisis ikatan antara kuersetin dengan NS3 dan NS5. protein dalam silika. Metode: Penelitian ini menggunakan metode focus assay untuk menghitung persentase hambatan dan menggunakan spektrofotometer dengan panjang gelombang 490 nm untuk menilai absorbansi dan mendapatkan nilai viabilitas sel. Pengujian in silico dilakukan dengan menggunakan software Autodock Tools 1.5.6 untuk melihat hasil docking protein NS3 dan NS5 terhadap quercetin. Hasil: Persentase penghambatan quercetin pada stadium pasca infeksi sebesar 62,54%, sedangkan pada stadium pra pasca infeksi sebesar 36%. Uji viabilitas sel pada stadium pasca infeksi kuersetin sebesar 94,68%, sedangkan pada stadium pra pasca infeksi sebesar 72,95%. Hasil uji docking in silico protein NS3 dengan kuersetin diperoleh energi ikatan, koefisien hambat, dan ikatan hidrogen pada konformasi terbaik berturut-turut -5,43 kkal/mol, 104,65 M, dan 4. koefisien hambat, dan ikatan hidrogen pada konformasi terbaik adalah -7,57 kkal/mol, 2,81 M, dan 5. Kesimpulan: Hasil penelitian menunjukkan bahwa persentase penghambatan yang dimiliki kuersetin terhadap replikasi DENV pada tahap pasca infeksi tinggi, sedangkan pada tahap pra infeksi, pasca infeksi infeksi memiliki persentase penghambatan yang rendah. Nilai viabilitas sel pada tahap pasca infeksi dan pada tahap pra pasca infeksi tinggi dengan nilai terbesar pada tahap pasca infeksi. Quercetin dapat mengikat lebih efektif ke NS5 daripada ke NS3.

---

Introduction: Cases of Dengue Hemorrhagic Fever (DHF) in Indonesia in 2017 reached 68,407 cases with the province with the highest number of dengue cases being West Java Province. The spread of dengue fever in Indonesia is increasingly widespread and can generally be transmitted to children aged less than 15 years. However, the treatment recommended by WHO for dengue fever is only symptomatic. In fact, with the dengue antiviral, the viral load in the body will quickly decrease and reduce the risk of disease severity and disease spread. The purpose of this study was to determine the potential of quercetin as an antiviral for Dengue by looking at the effect of quercetin administration at the post-infection and pre-infection stages in vitro and to analyze the bond between quercetin and NS3 and NS5. protein in silica. Methods: This study used the focus assay method to calculate the percentage of resistance and used a spectrophotometer with a wavelength of 490 nm to assess absorbance and obtain cell viability values. In silico testing was carried out using Autodock Tools 1.5.6 software to see the results of NS3 and NS5 protein docking against quercetin. Results: The percentage of quercetin inhibition in the post-infection stage was 62.54%, while the pre-post-infection stage was 36%. The cell viability test at the post-infection stage of quercetin was 94.68%, while at the pre-post-infection stage it was 72.95%. The results of the docking in silico protein NS3 with quercetin obtained bond energy, inhibition coefficient, and hydrogen bonding at the best conformation -5.43 kcal/mol, 104.65 M, and 4. inhibition coefficient, and hydrogen bonding at the best conformation. were -7.57 kcal/mol, 2.81 M, and 5. Conclusion: The results showed that the percentage of inhibition of quercetin on DENV replication in the post-infection stage was high, whereas in the pre-infection, post-infection stage, the percentage of inhibition was high. low. The value of cell viability at the post-infection stage and at the pre-post-infection stage was high with the greatest value at the post-infection stage. Quercetin can bind more effectively to NS5 than to NS3."

"Pendahuluan: Infeksi virus dengue merupakan infeksi yang paling banyak terjadi di Indonesia. Terapi infeksi dengue umumnya bersifat suportif berupa terapi cairan dan simptomatik. Berdasarkan penelitian sebelumnya, quercetin diketahui memiliki potensi sebagai antiviral dengue. Namun, mekanisme penghambatannya belum diketahui. Penelitian ini bertujuan untuk menilai persentase hambatan quercetin pada mekanisme penghambatan reseptor dan penempelan virus dengue serotipe 2 (DENV-2), persentase viabilitas sel terhadap quercetin, serta ikatan energi antara quercetin dengan protein E pada DENV secara in silico. Metode: Senyawa diuji secara in vitro terhadap DENV-2 menggunakan sel Vero. Dilakukan dua jenis pengujian, yaitu uji penghambatan reseptor dan penempelan virus melalui uji fokus dan uji viabilitas sel melalui uji MTT. Konsentrasi quercetin yang digunakan sebagai uji adalah sebesar 2 kali IC50 (36,81 µg/ml). Pengujian hambatan secara in silico dengan menggunakan software Autodock Tools - 1.5.6. Hasil: Nilai persentase penghambatan pada reseptor dan penempelan DENV dengan quercetin adalah 23,53% dan 45%. Persentase viabilitas sel vero terhadap quercetin pada penghambatan tahap pra-infeksi adalah 109,82%. Interaksi antara quercetin dan protein E DENV memiliki nilai ikatan energi dan konstanta inhibisi pada konformasi terbaik sebesar -4,89 kkal/mol dan 0,26 mM. Kesimpulan: Quercetin berpotensi sebagai antiviral dengue melalui mekanisme penghambatan pada tahap pra-infeksi, terutama penghambatan penempelan virus

---

Introduction: Viral dengue infection is the most common infection in Indonesi. Nowadays, management of DHF is only supportive care, i.e, fluid and symptomatic therapy. Based on previous research, quercetin has potency as antiviral dengue, but the mechanism is still unknown. Thus, the purpose of this research is to evaluate the percentage of reseptor inhibition and dengue serotype 2 virus (DENV-2) attachments inhibition with quercetin, cell viability percentage against quercetin, and energy bond between quercetin and protein E DENV in silico. Method: The compound was tested in vitro against DENV-2 using Vero Cells. There were 2 type of tests, receptor and DENV attachment inhibitory test using focus assay and viability test using MTT assay. The quercetin concentration was 2 times IC50 (36,81µg/ml). In silico study was conducted using Autodock Tools – 1.5.6. Results: Inbitory percentage of reseptor and DENV attachment with quercetin were 23,53% and 45%. Vero cell viability against quercetin in pre-infection step was 109,82%. Energy bond and inhibition constanta between quercetin and protein E DENV were -4,89 kkal/mol and 0,26 mM. Conclusion: This study shows that quercetin has potency as antiviral dengue through DENV attachment inhibition.

"

"Demam berdarah merupakan penyakit infeksi yang disebabkan oleh virus dengue dengan tipe DENV-1, DENV-2, DENV-3, dan DENV-4. Antigen dari masing-masing tipe virus berbeda-beda, sehingga sampai saat ini belum ditemukan obat-obatan paten yang ampuh dalam melawan virus dengue. Penelitian secara in silico dilakukan sebagai penelitian pendahuluan untuk mempermudah pencarian senyawa penuntun untuk dilanjutkan pengujian secara in vitro dan in vivo. Senyawa bioflavonoid diantaranya fisetin, galangin, dan myricetin. Penelitian dilakukan untuk melihat potensi ligan fisetin, galangin, dan myricetin di mana variabel kontrol adalah quercetin terhadap Rdrp dari virus dengue. Metode penelitian menggunakan penambatan molekuler dan dinamika molekuler. Hasil simulasi senyawa flavonol dibandingkan dengan quercetin, dengan parameter penilaian penambatan molekuler, energi ikatan, Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF), dan kontak ligan-target. Hasil nilai penambatan molekuler untuk masing-masing ligan terendah yaitu myricetin, fisetin, quercetin, dan galangin dengan nilai docking score berturut-turut yaitu -10,145 kcal/mol, -9,796 kcal/mol, -8,513 kcal/mol, dan -8,036 kcal/mol. Hasil MM-GBSA energi ikatan terbaik adalah ligan fisetin, quercetin, myricetin, dan galangin dengan nilai ikatan energi bebas secara berturut-turut yaitu -60,65 kcal/mol, -57,83 kcal/mol, -57,19 kcal/mol, dan -51,36 kcal/mol. Hasil dari studi ini memprediksi bahwa quercetin tetap menjadi inhibitor terhadap target RNA dependent RNA polymerase (Rdrp) yang lebih baik dibandingkan Fisetin, Galangin, dan Myricetin.

---

Dengue fever is an infectious disease caused by the dengue virus with types DENV-1, DENV-2, DENV-3, and DENV-4. The antigen of each virus type is different, so that until now there has not been found any patent drugs that are effective against the dengue virus. In silico research was conducted as a preliminary study to facilitate the search for guiding compounds to be continued in vitro and in vivo testing. Bioflavonoid compounds include fisetin, galangin, and myricetin. The study was conducted to see the potential of fisetin, galangin, and myricetin ligands in which the control variable was quercetin against Rdrp from the dengue virus. The research method uses molecular docking and molecular dynamics. The simulation results of flavonol compounds were compared with quercetin, with parameter value of the docking score, bond energy, Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF), and contact ligand-target. The results of the lowest molecular docking values for each ligand were myricetin, fisetin, quercetin, and galangin with docking scores of -10.145 kcal/mol, -9.796 kcal/mol, -8.513 kcal/mol, and -8.036 kcal/mol respectively. The best binding energy MM-GBSA results were ligands fisetin, quercetin, myricetin, and galangin with free energy bond values -60.65 kcal/mol, -57.83 kcal/mol, -57.19 kcal/mol, and -51.36 kcal/mol respectively. The results of this study predict that quercetin remains a better inhibitor against RNA dependent RNA polymerase (RdRp) targets than Fisetin, Galangin, and Myricetin"

" ABSTRAK Dengue Hemorrhagic Fever (DHF) are viral diseases transmitted by mosquito vector spreads fastest in the world. Cause of dengue fever are RNA virus family Flaviviridae called dengue virus (DENV). DENV genome encodes three structural proteins, capsid (C), membrane proteins (prM), envelope protein (E) and seven nonstuktural protein NS1, NS2a, NS2b, NS3, NS4a, NS4B, and NS5. NS3 protein contains many epitopes that can be recognized by the humoral and cellular immune system. Therefore NS3 protein is a potential target for development of dengue vaccines. This study begins by sequencing NS3 gene DENV-4 IDS 96/10. Phylogenetic analysis and epitope analysis were done from the result of sequencing. Phylogenetic analysis showed IDS 96/10 are in one clade with strains isolated rom China (2010), Singapore (2010) and Thailand (2000). NS3 gene DENV-4 IDS 96/10 contained epitopes recognized by CD4+ T cell that is epitope # 3 on the position of amino acids (213-227), # 9A (243-257), # 4 (251-265), # 5 (258-272), # 6 (266-280), # 7 (273-287) which has the same amino acid sequence comparison between strains. At position # 8 epitope (281-295) there are variation of amino acid sequence . Amino acids at positions 500-508 is recognized by CD8 + lymphocytes have the same sequence between strains were compared, and the amino acids at positions 526-531 which recognised by has the same amino acid sequence comparison between strains. Recognition of these epitopes by T lymphocytes and B lymphocytes can be the basis for the development of vaccines, especially vaccines for the Indonesian strain. Cloning of NS3 gene IDS 96/10 were done by using 3 strategies, digestion sticky end of vector and insert, digestion blunt end of vector and digestion blunt end vector then didefosforilation using CIAP. Three of these strategies have not been able to produce a recombinant plasmid pUMVD-4aNS3. Further optimization needs to be done to obtain clones containing the recombinant plasmid.

---

ABSTRACTDemam Berdarah Dengue (DBD) adalah penyakit yang disebabkan virus dengan vektor nyamuk yang paling cepat menyebar di duniaGenom DENV terdiri dari tiga protein struktural yaitu capsid (C), protein membran (prM), dan protein envelop (E) serta tujuh gen protein nonstuktural yaitu NS1, NS2a, NS2b, NS3, NS4a,NS4b dan NS5. Protein NS3 mengandung epitop yang dapat dikenali oleh sistem imun humoral maupun selular. Oleh karena itu, protein NS3 merupakan target potensial bagi pengembangan vaksin dengue. Penelitian ini diawali dengan sekuensing pada gen NS3 DENV-4 IDS 96/10. Dari hasil sekuensing dilakukan analisis filogenetik dan analisis epitop. Analisis filogenetik menunjukkan gen NS3 IDS 96 /10 berada dalam satu clade dengan strain yang diisolasi dari Cina (2010), Singapore (2010) dan Thailand (2000). Pada gen NS3 DENV-4 IDS 96/10 terdapat epitop yang dapat dikenali oleh sel limfosit T CD4+ yaitu epitop #3 pada posisi asam amino (213-227) , #9A (243-257), #4 (251-265), #5 (258-272), # 6 (266-280), #7 (273-287) yang mempunyai urutan asam amino sama antar strain yang dibandingkan. Pada posisi epitop #8 (281-295) terdapatvariasi urutan asam amino. Asam amino pada posisi CD8+ mempunyai urutan yang sama antar strain yang dibandingkan,dan asam amino pada posisi 526-531 yang dikenali oleh limfosit B mempunyai urutan asam amino yang sama antar strain yang dibandingkan. Pengenalan epitop- epitop tersebut oleh limfosit T dan limfosit B menjadi dasar pengembangan vaksin khususnya vaksin yang khusus untuk strain Indonesia. Dilakukan pengklonaan gen NS3 IDS 96/10 dengan menggunakan 3 strategi, yaitu dengan digesti vektor dan insert dengan ujung sticky end, digesti vektor dengan ujung blunt end dan digesti vektor dengan ujung blunt end kemudian didefosforilasi menggunakan metode CIAP. Dengan ketiga strategi tersebut belum dapat menghasilkan plasmid rekombinan pUMVD-4aNS3. Perlu dilakukan optimasi lebih lanjut untuk mendapatkan klon yang berisi plasmid rekombinan.Demam Berdarah Dengue (DBD). Penyebab DBD adalahvirus RNA famili flaviviridae yang disebut virus dengue (DENV).500-508 dikenali oleh sellimfosit TCD8+ mempunyai urutan yang sama antar strain yang dibandingkan,dan asam amino pada posisi 526-531 yang dikenali oleh limfosit B mempunyai urutan asam amino yang sama antar strain yang dibandingkan. Pengenalan epitop- epitop tersebut oleh limfosit T dan limfosit B menjadi dasar pengembangan vaksin khususnya vaksin yang khusus untuk strain Indonesia. Dilakukan pengklonaan gen NS3 IDS 96/10 dengan menggunakan 3 strategi, yaitu dengan digesti vektor dan insert dengan ujung sticky end, digesti vektor dengan ujung blunt end dan digesti vektor dengan ujung blunt end kemudian didefosforilasi menggunakan metode CIAP. Dengan ketiga strategi tersebut belum dapat menghasilkan plasmid rekombinan pUMVD-4aNS3. Perlu dilakukan optimasi lebih lanjut untuk mendapatkan klon yang berisi plasmid rekombinan."