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"[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

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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.]"

"[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.

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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.]"

"[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.

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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."

"[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: 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

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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.

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"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.

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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."

"Infeksi virus dengue (DENV) masih merupakan masalah di seluruh wilayah Indonesia. Diperkirakan sebanyak 2,5 juta jiwa rentan terinfeksi DENV. Telah diupayakan kontrol transmisi DENV namun tidak dapat menekan transmisi penyakit. Terapi definitif dengue belum ada, padahal kadar virus dalam tubuh berhubungan dengan keluaran keparahan penyakit. Oleh sebab itu, penanganan infeksi DENV dititikberatkan pada antiviral dan vaksin. Achyranthes aspera merupakan tanaman obat yang diketahui mengandung alkaloid, sterol, triterpene, flavonoid, dan kumarin. Tanaman ini menunjukkan aktivitas antibakteri, antifungsi, antioksidan dan antiviral terhadap Epstein Barr Virus. Penelitian ini akan memperlihatkan efek ekstrak daun Achyranthes aspera terhadap replikasi DENV in vitro dengan mencari IC50,CC50, dan Selectivity Index (SI). Sel Huh7it-1 diinfeksikan dengan DENV yang telah diberi ekstrak dengan berbagai konsentrasi: 10, 20, 40, 80, 160, 320 μg/ml. Nilai IC50 didapatkan menggunakan metode Focus Assay, sementara CC50 dengan uji MTT. Data kemudian dianalisis dengan uji Kruskall-Wallis. Hasil analisis menunjukkan IC50 ekstrak sebesar 43,29 μg/ml dan CC50 sel tidak terinfeksi sebesar 239,69 μg/ml. Kemudian didapatkan Indeks Selektivitas sebesar 5,53. Hasil uji kemaknaan menunjukkan semua konsentrasi terdapat perbedaan kecuali konsentrasi 20 dan 10 μg/ml. Kesimpulannya, ekstrak daun Achyranthes aspera menunjukkan efek inhibisi terhadap replikasi DENV dan tidak bersifat toksik terhadap sel pada konsentrasi inhibisi, sehingga dapat dikembangkan sebagai antiviral dimasa mendatang.

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Dengue virus (DENV) infection is still a major problem in almost all area of Indonesia. Approximately, 2.5 billion people are vulnerable to be infected. The efforts to control DENV transmission had been done but they are not enough. The amount of virus infecting the body has a positive correlation with the severity of the disease yet definitive therapy has not yet been found. Thus, treatments developed for dengue are mainly focusing on antivirals and vaccines.

Achyranthes aspera is a medicinal plant which contains alkaloid, sterol, triterpene, flavonoid, and coumarine. Previous studies show that the plant has antibacterial, antifungal, antioxidant activities as well as antiviral to Epstein Barr Virus.

This research was conducted to evaluate the antiviral potency of Achyranthes aspera through IC50, CC50, and Selectivity Index (SI). Huh7it-1 cells were infected with DENV which had been mixed with extracts in various concentration: 10,20,40,80,160,320 μg/ml. IC50 was determined by Focus Assay while MTT test was used to determine CC50. Data were analyzed using Kruskal-Wallis test.

The results showed the IC50 and CC50 of the extract were 43.29 μg/ml and 239.69 μg/ml respectively and Selectivity Index 5.53. There was a significant difference (p<0,05) in all concentrations except 20 and 10 μg/ml. The leaf extract of Achyranthes aspera showed inhibition against DENV replication and was not toxic for cells. Thus, it could be developed as antivirals in the future."

"[Penyakit akibat virus dengue (DENV) masih menjadi masalah kesehatan diIndonesia. Hingga saat ini belum ada terapi definitif untuk infeksi DENV. Berbagaipenelitian dilakukan untuk mencari antiviral terhadap DENV. Salah satu jenistumbuhan yang memiliki potensi antiviral adalah Calophyllum macrophyllum(C.macrophyllum). Penelitian ini akan melihat efek antiviral yang dimiliki olehekstrak kulit batang C.macrophyllum terhadap DENV. Efeknya sebagai antiviralakan dilihat dari nilai IC50 (kemampuan inhibisi replikasi) dan CC50 (tingkatsitotoksisitas). Perbandingan antara nilai CC50 terhadap IC50 akan menghasilkannilai indeks selektivitas (SI). Penelitian ini akan dilakukan secara in vitromenggunakan sel Huh7it-1 yang diinfeksikan DENV. Konsentrasi ekstrak yangdigunakan adalah 10, 20, 40, 80, 160, dan 320 μg/mL. Metode Focus Assaydigunakan untuk mendapatkan nilai IC50 dan MTT Assay untuk mencari nilaiCC50. Nilai IC50 yang didapat sebesar 49,75 μg/ml dan CC50 dari sel tanpa infeksiDENV sebesar >320 μg/ml. Nilai SI yang didapat sebesar >6,43. Analisis statistikmenunjukkan perbedaan pada semua konsentrasi. Dapat disimpulkan bahwaekstrak kulit batang C.macrophyllum memiliki efek inhibisi terhadap replikasiDENV in vitro dan efek sitotoksik yang kecil, sehingga memiliki potensi sebagaiantiviral DENV., Disease caused by dengue virus (DENV) is still a major health problem inIndonesia. There is no definitive therapy for DENV infection. Many researcheshave been done to search for DENV antivirus. One of plants with potential antiviraleffect is Calophyllum macrophyllum (C.macrophyllum). This research was done toevaluate antiviral effect of Calophyllum macrophyllum bark extract on DENV.Antiviral effect was evaluated by IC50 (replication inhibition property) value andCC50 (Cytotoxic level) value. The selectivity index (SI) was the ratio betweenCC50 and IC50. This research was done by in vitro method with Huh7it cells thatwere infected by DENV. Extract concentrations used in this research were 10, 20,40, 80, 160, and 320 μg/mL. Focus assay technique was used to determine IC50value and MTT assay technique for CC50 value. The value of IC50 was 49.75 μg/mland CC50 from uninfected cells was >320 μg/ml. The value of SI was >6.43.Statistical analysis showed significant difference in all concentrations. It could beconcluded that bark extract of C.macrophyllum had inhibition property on DENVreplication in vitro with minimum cytotoxic effect.]"

"ABSTRAKAngka insidensi demam dengue di dunia masih tinggi, terutama di Asia, khusunya Indonesia. Angka insidensi demam dengue di Indonesia cenderung meningkat setiap tahunnya dengan angka insidensi pada tahun 2014 yaitu 83,34/100.000 penduduk. Sampai saat ini belum terdapat obat antiviral terhadap DENV sehingga penanganan demam dengue hanya sebatas terapi suportif. Dengan adanya agen antiviral, akan menurunkan angka morbiditas dan mortalitas dari demam dengue. Penelitian ini merupakan studi eksperimental yang menggunakan DENV serotipe 2 strain New Guinea C dan sel Huh7it-1 untuk mengetahui aktivitas antiviral fraksi n-heksana ekstrak daun kenikir Cosmo caudatus terhadap DENV-2. Dilakukan uji viabilitas sel Huh7it-1 dengan metode MTT assay untuk mengetahui tingkat toksisitas ekstrak. Dari uji ini didapatkan nilai half-cytotoxic concentration CC50 . Half-inhibitory concentration IC50 merupakan kemampuan ekstrak untuk menghambat replikasi DENV yang didapat melalui focus assay. Aktivitas antiviral digambarkan melalu nilai indeks selektivitas SI yang merupakan hasil perbandingan CC50 dengan IC50. Nilai CC50, IC50, dan SI dari fraksi n-heksana daun Cosmos caudatus sebesar 33,247 g/ml, 1,497 g/ml, dan 22,209 secara berurutan. Sehingga, fraksi n-heksana ekstrak daun C. caudatus memiliki aktivitas antiviral yang cukup baik terhadap DENV-2 secara in vitro

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ABSTRACTDengue fever incidence rate in the world is still high, with the highest number in Asia, especially Indonesia. Dengue fever incidence rate in Indonesia tends to increase year by year. Even in 2014, the incidence rate reached 83,34 100.000 population. Until now, there is still no availabe antiviral agents againts DENV. Therefore, DENV treatment is only limited to supportive therapy. It has been concluded that the presence of antiviral agents will decrease morbidity and mortality rate of dengue fever. This is an experimental study which used DENV 2 New Guinea Strain C and Huh7it 1 cell to find out antiviral activity of n hexane fraction of Cosmos caudatus against DENV 2. Toxicity level of the extract was obtained from viability test of Huh7it 1 with MTT assay method. From this test, we obtained the half cytotoxic concentration CC50 . The ability of the extract to inhibit DENV replication is depicted from half inhibitory concentration IC50 which was performed with focus assay method. Antiviral activity is depicted from the value of selectivity index SI which is a ratio between CC50 and IC50. The value of CC50, IC50, and SI are 33,247 g ml, 1,497 g ml, and 22,209, respectively. N hexane fraction of C. caudatus leaf extract showed satisfactory antiviral activity against DENV 2 in vitro."