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Kazmierski, Wieslaw M.
Abstrak :
This book focuses on new small molecule approaches to combat viral infections. The chapters describe the discovery and development from bench through the clinic of relatively recently-approved antiviral drugs and compounds in advanced clinical development. Organized by a virus (such as HIV, HCV, RSV, influenza, HBV and CMV) and written by top academic and industrial authorities in the field, the book provides a unique opportunity to study, understand and apply discovery and development principles and learning without the need for an individual to research, analyze and synthesize all immense sourcing references. Topics showcase challenges and solutions of issues encountered, offeringtremendous experience accumulated over many years of research that will be particularly useful to basic and bench scientists as well as clinicians as they continue discovering and developing new drugs and therapies.
New Jersey: John Wiley & Sons, 2011
e20375714
eBooks  Universitas Indonesia Library
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Clercq, Erik De
Abstrak :
By focusing on general molecular mechanisms of antiviral drugs rather than therapies for individual viruses, this ready reference provides the critical knowledge needed to develop entirely novel therapeutics and to target new viruses. It begins with a general discussion of antiviral strategies, followed by a broad survey of known viral targets, such as reverse transcriptases, proteases, neuraminidases, RNA polymerases, helicases and primases, as well as their known inhibitors. The final section contains several cases studies of recent successful antiviral drug development. Edited by Erik de Clercq, the world authority on small molecule antiviral drugs, who has developed more new antivirals than anyone else.
Weinheim: Wiley-VCH Verlag, 2011
e20375713
eBooks  Universitas Indonesia Library
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Paulina Livia Tandijono
Abstrak :
ABSTRAK
Tingginya angka infeksi virus dengue (DENV) di Indonesia merupakan masalah kesehatan yang masih belum tertangani. Pengobatan infeksi DENV hingga saat ini masih mengandalkan imunitas penderita. Berbagai jenis antiviral DENV sedang dikembangkan, salah satunya menggunakan rekayasa genetika berbasis sekuens untranslated region (UTR). Namun data mengenai UTR DENV masih sedikit. Oleh karena itu, penulis melakukan penelitian untuk menganalisa sekuens dan filogenetik UTR DENV-1. Dalam penelitian ini, dua strain Indonesia dibandingkan dengan 25 strain dari GenBank menggunakan program Genetyx 5.1. Hasil penelitian ini menunjukan bahwa terdapat beberapa sekuens yang lestari, sehingga memenuhi kriteria sebagai target siRNA, yaitu 3’UAR, CS1, CS2, dan RCS2. Sementara sekuens 5’ UTR tidak memenuhi syarat siRNA karena ditemukan perubahan pada beberapa strain, termasuk strain Indonesia. Filogenetik menggunakan UTR tidak sesuai dengan filogenetik envelope dan tidak dapat digunakan untuk menjelaskan pola penyebaran DENV-1.
ABSTRACT
High prevalence of dengue virus (DENV) infection still become an unresolved issue in Indonesia. Treatment for DENV infection relies heavily on natural immunity. Various DENV antivirals are on development, one of them is untranslated region (UTR)-sequence-based. However, there is only a few number of data available on UTR DENV. Therefore, this research was done to analyze the sequence and phylogenetic of UTR DENV-1. Two Indonesia strains were compared with 25 strains from GenBank using the Genetyx 5.1 program. There are four conserved sequences that fill criteria as siRNA targets, which are 3’UAR, CS1, CS2, and RCS2. 5’UTR sequence does not fill the siRNA criteria because mutations were found within some strains, including Indonesia strains. Phylogenetic using UTR does not fit envelope phylogenetic and can not be used to explain the DENV-1 pattern.
2014
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UI - Skripsi Membership  Universitas Indonesia Library
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Muhammad Arif Sanusi
Abstrak :
Infeksi dengue masih merupakan masalah kesehatan di Indonesia sebagai negara endemik. Sampai saat ini, belum ditemukan terapi definitif sebagai tatalaksana infeksi dengue. Penelitian untuk pengembangan antivirus dengue sudah banyak dilakukan. Ekstrak Calophyllum canum, sebagai salah satu tanaman yang tumbuh di Kalimantan, ditemukan memiliki efek anti mikroganisme. Penelitian dilakukan untuk menguji efek antiviral dari crude extract batang C. canum fraksti etil asetat terhadap replikasi virus dengue serotipe-2 (DENV-2) pada sel Huh7it-1 dengan focus assay dan MTT assay untuk menguji sitotoksitas pada sel tidak terinfeksi. Nilai IC50 dari ekstrak C. canum pada sel Huh7it-1 adalah 123,96 μg/mL dan nilai CC50 adalah 620,57 μg/mL. Indeks selektivitas adalah 5,01. Pada focus assay terdapat perbedaan bermakna antara tiap perlakuan dengan kontrol (p<0,001) namun pada MTT assay tidak terdapat perbedaan bermakna antara tiap perlakuan dengan kontrol (p≥0,05). Crude extract dari batang C. canum memiliki efek inhibisi terhadap replikasi DENV-2 secara in Vitro pada sel Huh7it-1. ...... Until now, dengue infection is still a health concern in Indonesia. There is no definite treatment for dengue infection. The development of dengue antivirus using natural extract of plant have been conducted. Calophyllum canum, a plant that grow in Kalimantan was discovered to have anti-microorganism effect. In present study, crude extract of C. canum stem in ethyl acetate fraction was used to examine the antiviral effect on dengue virus seroptype-2 (DENV-2) replication on Huh7it-1. The inhibition of DENV-2 replication was determined by focus assay. The cytotoxicity of uninfected cells by MTT assay. The IC50 value of C. canum on Huh7it-1 cells was 123.96 μg/mL and the CC50 value was 620.57 μg/mL. The selectivity index was 5.01. There was significant difference on focus assay between all concentration with control (p<0.001), but there was no significant difference in MTT assay (p≥0.05). Crude extract of C. canum stem showed inhibition effect on DENV-2 replication in vitro on Huh7it-1 cells.
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2015
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UI - Skripsi Membership  Universitas Indonesia Library
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Kartika Laksmi H
Abstrak :
[DENV merupakan sebuah virus yang penularannya melalui vektor nyamuk, yaitu Aedes aegypti. Virus ini terdiri dari 4 tipe, yaitu DENV-1, DENV-2, DENV-3, dan DENV-4. Infeksi DENV banyak terjadi pada negara dengan iklim tropis, diantaranya seperti Karibia, Asia Tenggara, serta Pasifik Barat. Indonesia termasuk salah satu negara dengan endemis infeksi DENV di seluruh wilayahnya. Hingga saat ini, tatalaksana yang diberikan untuk pasien dengan infeksi DENV masih berupa tatalaksana suportif dikarenakan belum ditemukan obat yang efektif untuk mengobati keempat tipe DENV. Ekstrak daun Shorea spp. disinyalir memiliki kemampuan untuk menginhibisi DENV sehingga dapat digunakan sebagai antiviral. Pada penelitian ini, sel Huh7It-1diinfeksikan dengan DENV dan diberikan ekstrak Shorea spp. dengan berbagai konsentrasi. Efektifitas ekstrak diteliti dengan menggunakan konsentrasi 320 μg/ml, 160 μg/ml, 80 μg/ml, 40 μg/ml, 20 μg/ml, dan 10 μg/ml. Efek inhibisi diuji menggunakan metode Focus Assay. Sedangkan efek sitotoksik diuji menggunakan metode MTT Assay. Pada penelitian ini didapatkan nilai sitotoksik (CC50) ekstrak terhadap sel dan nilai inhibisi (IC50) ekstrak terhadap DENV, yaitu nilainya sebesar 150,85 μg/ml dan 23,22 μg/ml. Berdasarkan nilai IC50 dan CC50, didapatkan nilai Selectivity Index (SI) sebesar 6,496. Hal ini menunjukkan bahwa ekstrak daun Shorea spp. memiliki efek inhibisi terhadap DENV dan dapat dikembangkan sebagai antiviral terhadap DENV di masa mendatang.;DENV is a virus transmitted through mosquito vectors, named Aedes aegypti. This virus consists of four types, which is DENV-1, DENV-2, DENV-3 and DENV-4. DENV infection are more prevalent in countries with tropical climates, such as the Caribbean, Southeast Asia, and the Western Pacific. Indonesia is one of the country with endemic DENV infection founded in the entire region. Until now, the treatment which is given to patients with DENV infection is still in the form of supportive treatment, because effective drugs to treat the four types of DENV has not been discovered yet. Leaf extract of Shorea spp. allegedly has the ability to inhibit DENV which acts as an antiviral. In this study, Huh7lt cell was infected with DENV and was given Shorea spp. extracts in various concentrations from 320 μg/ml, 160 μg/ml, 80 μg/ml, 40 μg/ml, 20 μg/ml, and 10 μg/ml. Inhibitory effect was tested by using focus assay, while cytotoxic effect was tested by using MTT assay. In this study, the extract's cytotoxic value (CC50) against cell and inhibition values (IC50) against DENV was determined, with the results 150.85 μg/ml and 23.22 μg/ml. Based on value of IC50 dan CC50, Selectivity Inde x (SI) score was 6,496. This indicates that the leaf extract of Shorea spp. has inhibitory effects against DENV and could be developed as an antiviral againsts DENV in the future;DENV is a virus transmitted through mosquito vectors, named Aedes aegypti. This virus consists of four types, which is DENV-1, DENV-2, DENV-3 and DENV-4. DENV infection are more prevalent in countries with tropical climates, such as the Caribbean, Southeast Asia, and the Western Pacific. Indonesia is one of the country with endemic DENV infection founded in the entire region. Until now, the treatment which is given to patients with DENV infection is still in the form of supportive treatment, because effective drugs to treat the four types of DENV has not been discovered yet. Leaf extract of Shorea spp. allegedly has the ability to inhibit DENV which acts as an antiviral. In this study, Huh7lt cell was infected with DENV and was given Shorea spp. extracts in various concentrations from 320 μg/ml, 160 μg/ml, 80 μg/ml, 40 μg/ml, 20 μg/ml, and 10 μg/ml. Inhibitory effect was tested by using focus assay, while cytotoxic effect was tested by using MTT assay. In this study, the extract's cytotoxic value (CC50) against cell and inhibition values (IC50) against DENV was determined, with the results 150.85 μg/ml and 23.22 μg/ml. Based on value of IC50 dan CC50, Selectivity Inde x (SI) score was 6,496. This indicates that the leaf extract of Shorea spp. has inhibitory effects against DENV and could be developed as an antiviral againsts DENV in the future, DENV is a virus transmitted through mosquito vectors, named Aedes aegypti. This virus consists of four types, which is DENV-1, DENV-2, DENV-3 and DENV-4. DENV infection are more prevalent in countries with tropical climates, such as the Caribbean, Southeast Asia, and the Western Pacific. Indonesia is one of the country with endemic DENV infection founded in the entire region. Until now, the treatment which is given to patients with DENV infection is still in the form of supportive treatment, because effective drugs to treat the four types of DENV has not been discovered yet. Leaf extract of Shorea spp. allegedly has the ability to inhibit DENV which acts as an antiviral. In this study, Huh7lt cell was infected with DENV and was given Shorea spp. extracts in various concentrations from 320 μg/ml, 160 μg/ml, 80 μg/ml, 40 μg/ml, 20 μg/ml, and 10 μg/ml. Inhibitory effect was tested by using focus assay, while cytotoxic effect was tested by using MTT assay. In this study, the extract's cytotoxic value (CC50) against cell and inhibition values (IC50) against DENV was determined, with the results 150.85 μg/ml and 23.22 μg/ml. Based on value of IC50 dan CC50, Selectivity Inde x (SI) score was 6,496. This indicates that the leaf extract of Shorea spp. has inhibitory effects against DENV and could be developed as an antiviral againsts DENV in the future]
[;Fakultas Kedokteran Universitas Indonesia, Fakultas Kedokteran Universitas Indonesia], 2015
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UI - Skripsi Membership  Universitas Indonesia Library
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Tsabita Annisa
Abstrak :
Penyakit demam berdarah merupakan salah satu penyakit utama yang tergolong dalam penyakit infeksi tropis di dunia dan di saat yang bersamaan, masih kurang adanya vaksin yang disetujui dan terapi antiviral yang dapat mengimunisasi dan menyembuhkan pasien dari penyakit tersebut. Sampai saat ini, perawatan suportif adalah tata laksana yang paling efektif untuk infeksi virus dengue (DENV), sehingga strategi terapeutik dengan menggunakan ekstrak natural telah dikembangkan. Indonesia sangat kaya dengan aneka ragam tanaman yang memiliki potensi sebagai obat antiviral, seperti contohnya Artocarpus communis. Tujuan dari penelitian ini adalah menilai efek inhibitorik dari A. communis terhadap replikasi dan infeksi virus dengue. Dalam eksperimen ini, enam sampel sel Huh7it-1 diinfeksikan dengan DENV-2 NGC dan diberi perlakuan menggunakan berbagai konsentrasi dari ekstrak natural A.communis untuk menginvestigasi aktifitas antiviral extract tersebut. Cytotoxic effect dari ekstrak tersebut ditentukan oleh nilai 50% cytotoxic concentration (CC50) yang didapat dari cell viability (MTT) assay. Selain itu, focus assay digunakan untuk mencari nilai 50% inhibitory concentration (IC50) yang menentukan inhibitory effect. Eksperimen ini diakhiri dengan menghitung selectivity index (SI) untuk mengukur aktifitas antiviral dari ekstrak. Infeksi virus terhambat sangat efektif sebanyak 95.4% (p=0.0035) dengan perlakuan konsentrasi ekstrak tertinggi yaitu 80μg/ml. Namun, hambatan infeksi virus menurun dengan perlakuan konsentrasi ekstrak yang lebih rendah yaitu 40μg/ml, 20μg/ml, 10μg/ml dan 5μg/ml dengan inhibisi sebanyak 52.3% (p=0.0238), 12.6% (p=0.4408), 5.8% (p=0.5832) dan 2.1% (p=0.7881) secara urut. A. communis memiliki nilai IC50, CC50 dan SI yaitu 43.26μg/ml, 366.67μg/ml dan 8.48. Hasil yang didapatkan dari eksperimen ini menunjukkan bahwa pada konsentrasi yang tinggi, ekstrak natural A. communis memiliki properti antiviral terhadap virus dengue. Selain itu, ekstrak tersebut memiliki nilai CC50 yang tinggi yang menandakan level cytotoxicity yang rendah dan nilai SI yang signifikan,sehingga menunjukkan potensi yang baik sebagai agen antiviral terhadap DENV.
Dengue hemorrhagic fever is currently a major tropical and subtropical infection in the world with lack of approved vaccines as well as antiviral therapies to immunize and cure patients towards this disease. Up until now, supportive care is the only effective management with no promising therapeutic treatment available against dengue virus (DENV) infection, therefore development of therapeutic strategies using natural extracts have arisen. Indonesia is rich in plant varieties in which their natural extracts have the potential for antiviral drugs, for example Artocarpus communis. The aim of this study was to investigate antiviral properties present in the natural extract of A. communis against DENV infection. In the experiment, six replicates of Huh7it-1 cells were infected with DENV-2 NGC and given various concentrations of natural extracts to determine antiviral activity. The toxicity effects of the extract were determined by cell viability (MTT) assay to find 50% cytotoxic concentration (CC50). Focus assay was used to find 50% inhibitory concentration (IC50), which determined the inhibitory effect. We concluded the experiment with calculating the selectivity index (SI) to measure antiviral activity of the extract. Upon treatment with the highest extract concentration of 80μg/ml, the infection was inhibited impressively as much as 95.4% (p=0.0035). The inhibition of infection decreased with lower extract concentration of 40μg/ml, 20μg/ml, 10μg/ml and 5μg/ml as much as 52.3% (p=0.0238), 12.6% (p=0.4408), 5.8% (p=0.5832) and 2.1% (p=0.7881) respectively. The results also exemplified that A. communis has an IC50, CC50 and SI of 43.26μg/ml, 366.67μg/ml and 8.48. The results of this study indicate that the natural extract of Artocarpus communis shows some level of antiviral property towards dengue virus at high concentrations. Furthermore, it has a high CC50 value that signifies low cytotoxicity and a significant SI thus demonstrating a good potency as an antiviral agent against DENV.
Depok: Universitas Indonesia, 2014
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UI - Skripsi Membership  Universitas Indonesia Library
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Maria Nathania
Abstrak :
Infeksi yang disebabkan oleh virus dengue atau juga diketahui sebagai demam berdarah, adalah masalah kesehatan yang sangat signifikan dengan adanya sebanyak 150.000 kasus per tahun. saat ini, belum ada vaksin maupun antiviral yang ada untuk mencegah maupun untuk pengelolaan penyakit. Hal-hal ini lah yang meningkatkan urgensi untuk menginvestigasi kemungkinan adanya aktifitas antiviral dalam ekstrak natural yang dapat digunakan sebagai intervensi terapeutik. Garcinia dulcis (G. dulcis) adalah tumbuhan yang berasal dari Indonesia dan negara Asia Tenggara lainnya. Tumbuhan ini diketahui memiliki aktifitas antimalarial dan antioxidan yang tinggi. Tujuan dari riset ini adalah untuk meneliti efektifitas ekstrak daun G. dulcis sebagai antiviral terhadap virus dengue (DENV). Dalam percobaan ini, DENV dengan serotype 2 NGC dan Huh-7 cell line digunakan untuk antiviral assay. Maximal inhibitory concentration (IC50), didapatkan dengan cara memberikan perlakuan dengan berbagai konsentrasi G. dulcis (80μg/ml, 40μg/ml, 20μg/ml, 10μg/ml and 5μg/ml) terhadap sel Huh-7 yang sudah diinfeksikan oleh DENV-2 NGC. Jumlah inhibisi terhadap replikasi DENV ditentukan dengan menggunakan focus assay. Dimethyl sulfoxide (DMSO), digunakan sebagai kontrol positif. Sitotoksisitas (CC50) dicari menggunakan MTT assay. Pada perlakuan dengan konsentrasi G. dulcis sebesar 80μg/ml dan 40μg/ml, DENV terhambat secara signifikan sebanyak 92.8% (p=0.01) dan 71.3% (p=0.02) secara berurutan. Selanjutnya, pada konsentrasi 20μg/ml, DENV terhambat sebesar 11.7% (p=0.83). Hasil dari percobaan ini, menunjukkan bahwa IC50, CC50, dan SI dari G. dulcis adalah sebesar 44.7μg/ml, 314.8μg/ml, dan 7.04 secara berurutan. Ekstrak daun G. dulcis menunjukkan aktivitas penghambatan yang signifikan terhadap DENV pada konsentrasi 80 μg/ml dan 40 μg/ml dan sitotoksisitas yang rendah. Rendahnya sitotoksisitas merupakan karakteristik yang menguntungkan untuk menjadi antiviral. Maka, sub-fraksi dari G. dulcis harus dicari untuk dapat menemukan senyawa murni yang dapat mennghambat replikasi DENV dengan efektif. Selain itu, investigasi lebih lanjut pada batang, kulit dan benih G. dulcis dapat dilakukan. Ekstrak natural perlu diperlajari secara ekstensif perlu dilakukan untuk menemukan antiviral yang efektif untuk menangani infeksi DENV.
Dengue virus (DENV) infection is a major health problem in Indonesia, with more than 150,000 cases occurring annually. Currently, no approved vaccines or antivirals are available to prevent or manage the disease. This urges the need to investigate possible antiviral activity of natural extracts to be used as therapeutic management for DENV infection. Garcinia dulcis (G. dulcis) is a plant native to Indonesia and other Southeast Asia countries; it is known to have antimalarial and high antioxidant activities. The objective of this research is to investigate the effectivity of G. dulcis leaves extract as a viable antiviral against DENV. In this study, we used DENV serotype 2 NGC and Huh-7 cells line for antiviral assay. Maximal inhibitory concentration (IC50) was determined by applying various concentrations of G. dulcis (80μg/ml, 40μg/ml, 20μg/ml, 10μg/ml and 5μg/ml) to DENV-2 NGC-infected Huh-7 cells with 6 times replication. Inhibition of DENV replication was determined by focus assay from G. dulcis treated supernatant. We used dimethyl sulfoxide (DMSO) on dengue-infected cells as positive control. The cytotoxicity (CC50) was determined by MTT assay. Upon treatment with 80μg/ml and 40μg/ml of G. dulcis extract, DENV infection was significantly inhibited as much as 92.8% (p=0.01) and 71.3% (p=0.02) respectively. At concentrations of 20μg/ml, DENV was insignificantly inhibited by 11.7% (p=0.83). The result showed, that IC50, CC50, and SI of G. dulcis extract were 44.7μg/ml, 314.8μg/ml, and 7.04, respectively. G. dulcis leaves extract showed significant inhibitory effect towards dengue virus in vitro at concentrations of 80 μg/ml and 40 μg/ml and it has low cytotoxicity. Low cytotoxicity is a characteristic that can be advantageous for an antiviral agent. Thus, sub-fractions of G. dulcis leaves needs to be done to find pure compound that effectively inhibit DENV replication. Alternatively, further investigations on stems, barks and seeds of G. dulcis can also be done. Extensive studies on natural extracts should be continued to develop an antiviral in managing DENV infection.
Depok: Universitas Indonesia, 2014
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UI - Skripsi Membership  Universitas Indonesia Library
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Christian Marco Hadi Nugroho
Abstrak :
Latar Belakang: Avian influenza merupakan penyakit infeksius yang mudah menular secara aerosol. Salah satu subtipenya yakni H9N2 mewabah pertama kali di wilayah peternakan unggas di Indonesia pada tahun 2016 dan dilaporkan membawa gen yang cenderung menginfeksi sel mamalia. Antiviral berbasis sialidase dikembangkan sebagai pencegahan dan pengobatan infeksi virus saluran pernafasan seperti avian influenza yang membutuhkan sialic acid sebagai pintu masuknya virus ke dalam sel. Penelitian ini bertujuan mengembangkan antiviral berbasis sialidase asal bakteri Pasteurella multocida, khususnya terhadap infeksi subtipe H9N2. Metode: Penelitian diawali dengan kultur Pasteurella multocida yang secara genetik hanya mengandung satu jenis sialidase yakni NanB. Sialidase dipurifikasi melalui metode kloroform, dan dilanjutkan dengan ion exchange chromatography dan affinity chromatography. NanB sialidase yang dihasilkan diuji aktivitasnya pada suhu, pH dan lama waktu inkubasi yang berbeda. Uji toksisitas dan spesifisitas NanB sialidase dilakukan dengan menggunakan berbagai dosis sialidase pada media sel darah merah ayam dan kelinci serta sel MDCK. Dilanjutkan dengan uji hambatan infeksi virus avian influenza H9N2 dan ekspresi gen penyandi apoptosis sebagai respon sel terhadap infeksi avian influenza H9N2. Hasil: Pasteurella multocida B018 terbukti menghasilkan NanB sialidase dengan berat molekul sekitar 55 kDa. NanB sialidase yang dihasilkan bersifat stabil pada suhu 37℃ dan pH 5 hingga 7 meskipun mengalami penurunan aktivitas pada 72 jam inkubasi. Dosis 0.258 U/ml merupakan dosis toksik yang melisiskan sel darah merah dan merusak sel MDCK. Dosis efektif yang mampu menghirolisis sialic acid adalah 0.129 U/ml, namun NanB sialidase cenderung menghidrolisis sialic acid Neu5Acα(2,6)-Gal pada mamalia. Dosis tersebut juga mampu menghambat ikatan virus H9N2 pada sel darah merah serta menekan jumlah infeksi virus pada sel MDCK tanpa menyebabkan peningkatan ekspresi gen penyandi apoptosis sel. Kesimpulan: NanB Sialidase asal bakteri Pasteurella multocida berpotensi sebagai antivirus avian influenza melalui hilangnya sialic acid akibat proses hidrolisis yang terjadi. ......Background: Avian influenza is an infectious disease easily transmitted by aerosol. One of the subtypes, H9N2, first appeared in poultry farming areas in Indonesia in 2016 and was reported to carry a gene that tends to infect mammalian cells. Sialidase-based antivirals were developed to prevent and treat viral respiratory infections such as avian influenza, which require sialic acid as the entry point for viruses to enter cells. This study aims to develop a sialidase-based antiviral from the Pasteurella multocida, especially against infection with the H9N2 subtype. Methods: The research started with Pasteurella multocida culture, which contains only one type of sialidase, NanB. Sialidase was purified by the chloroform method and followed by ion-exchange chromatography and affinity chromatography. NanB sialidase was tested for its activity at different temperatures, pH, and incubation times. The toxicity and specificity test of NanB sialidase was carried out using various doses of sialidase on chicken and rabbit red blood cells and MDCK cells, followed by the inhibition test of avian influenza H9N2 virus infection and expression of apoptotic coding genes as a cell response to avian influenza H9N2 infection. Results: Pasteurella multocida B018 produced NanB sialidase with a molecular weight of about 55 kDa. The resulting NanB sialidase was stable at 37℃ and pH 5 to 7, although it decreased in activity at 72 hours of incubation. The dose of 0.258 U/ml is a toxic dose that lyses red blood cells and destroys MDCK cells. The effective dose capable of hydrolyzing sialic acid is 0.129 U/ml, but NanB sialidase tends to hydrolyze Neu5Acα(2,6)-Gal sialic acid in mammals. This dose also inhibited the binding of the H9N2 virus on red blood cells. It suppressed the number of viral infections in MDCK cells without increasing the expression of genes encoding cell apoptosis. Conclusion: NanB Sialidase from Pasteurella multocida has the potential as an antiviral for avian influenza through the loss of sialic acid due to the hydrolysis process
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2022
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UI - Disertasi Membership  Universitas Indonesia Library
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Haryo Satrio Muhammad
Abstrak :
[Saat ini tengah banyak studi yang dilakukan untuk menemukan antivirus dengue (DENV) dari ekstrak bebagai tumbuhan sebagai alternatif pengobatan terhadap infeksi DENV. Calophyllum flavoramulum (C. flavoramulum) merupakan tanaman yang banyak hidup di daerah Asia Tenggara ini memiliki kandungan dari turunan xanthone dan flavonoid yang memiliki potensi sebagai antivirus. Pada studi ini dilakukan evaluasi efek inhibisi dari fraksi etanol ekstrak daun C. flavoramulum terhadap DENV-2 strain New Guinea C (NGC). Efek inhibisi (IC50) dievaluasi dengan menggunakan focus assay. Sedangkan efek toksisitas (CC50) terhadap sel dievaluasi pada sel Huh7it-1 menggunakan metode MTT assay. Hasil dari studi ini menunjukan CC50 = 473,50ug/ml, IC50 = 41,74ug/ml, dan SI=11,33. Hasil tersebut menunjukan bahwa C. flavoramulum tidak toksik terhadap sel hidup dan memiliki nilai SI yang cukup tinggi sehingga efektif untuk digunakan sebagai antivirus dengue. Akan tetapi, perlu diteliti lebih lanjut mengenai kandungan aktif dalam C. flavoramulum yang memiliki aktivitas untuk menghambat replikasi DENV.;In recent years, several studies have been conducted to find dengue (DENV) antiviral from natural extract as an alternative management for dengue infection. Calophyllum flavoramulum(C. flavoramulum), one of South East Asia plants, contains derivates of flavonoid and xanthone where both have been known as potential dengue antivirals. This study evaluated inhibitory potential of ethanol extract from C. flavoramulum leaf to DENV-2 strain New Guinea C (NGC) through focus assay. Along with inhibitory effect (IC50), toxicity effect (CC50) to Huh7it-1 cell also evaluated through MTT assay. The result of this study shown IC50 = 41.74 μg/mL, CC50 = 473.50 μg/mL, and SI=11.33. In conclusion, extract of C. flavoramulum can be used selectively as a dengue antiviral, besides it is not toxic for living cells. More studies are needed to find its active ingredients which specifically have the ability to inhibit DENV replication.;In recent years, several studies have been conducted to find dengue (DENV) antiviral from natural extract as an alternative management for dengue infection. Calophyllum flavoramulum(C. flavoramulum), one of South East Asia plants, contains derivates of flavonoid and xanthone where both have been known as potential dengue antivirals. This study evaluated inhibitory potential of ethanol extract from C. flavoramulum leaf to DENV-2 strain New Guinea C (NGC) through focus assay. Along with inhibitory effect (IC50), toxicity effect (CC50) to Huh7it-1 cell also evaluated through MTT assay. The result of this study shown IC50 = 41.74 μg/mL, CC50 = 473.50 μg/mL, and SI=11.33. In conclusion, extract of C. flavoramulum can be used selectively as a dengue antiviral, besides it is not toxic for living cells. More studies are needed to find its active ingredients which specifically have the ability to inhibit DENV replication., In recent years, several studies have been conducted to find dengue (DENV) antiviral from natural extract as an alternative management for dengue infection. Calophyllum flavoramulum(C. flavoramulum), one of South East Asia plants, contains derivates of flavonoid and xanthone where both have been known as potential dengue antivirals. This study evaluated inhibitory potential of ethanol extract from C. flavoramulum leaf to DENV-2 strain New Guinea C (NGC) through focus assay. Along with inhibitory effect (IC50), toxicity effect (CC50) to Huh7it-1 cell also evaluated through MTT assay. The result of this study shown IC50 = 41.74 μg/mL, CC50 = 473.50 μg/mL, and SI=11.33. In conclusion, extract of C. flavoramulum can be used selectively as a dengue antiviral, besides it is not toxic for living cells. More studies are needed to find its active ingredients which specifically have the ability to inhibit DENV replication.]
[, Fakultas Kedokteran Universitas Indonesia], 2015
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Genanda Fisabilila
Abstrak :
ABSTRAK
Infeksi virus Dengue DENV masih menjadi masalah kesehatan global. Tingginya angka infeksi dan belum adanya vaksin maupun obat spesifik terhadap virus Dengue meningkatkan risiko kematian yang ditimbulkan. Tanaman Gonystylus bancanus banyak terdapat di wilayah Indonesia yang memiliki efek analgesik, antialergi, antiinflamasi, antibakteri, dan antivirus. Penelitian ini bertujuan untuk mengetahui aktivitas ekstrak daun Gonystylus bancanus dalam menghambat pertumbuhan virus Dengue serotipe 2 DENV-2 . Penelitian dilakukan secara in vitro menggunakan sel Huh 7.5 yang diinfeksi DENV-2 dengan multiplicity of infection m.o.i 0,5. Sampel penelitian terdiri dari kultur sel terinfeksi DENV-2 sebagai kontrol positif dan kelompok perlakuan dengan ekstrak daun Gonystylus bancanus pada konsentrasi 20 g/mL, 10 g/mL, 5 g/mL, 2,5 g/mL, dan 1,25 g/mL. Aktivitas antivirus dinilai berdasarkan jumlah fokus virus yang terbentuk pada proses immunostaining. Diperoleh hasil bahwa seluruh konsentrasi ekstrak daun Gonystylus bancanus yang diujikan secara signifikan menghambat replikasi DENV-2 p < 0,05 . Aktivitas penghambatan replikasi DENV-2 berbanding lurus dengan konsentrasi uji ekstrak daun Gonystylus bancanus dengan hambatan replikasi tertinggi terjadi pada konsentrasi 20 g/mL yang dapat menekan pertumbuhan virus sebesar 46,10 . Penelitian lebih lanjut dapat dilakukan untuk mengetahui senyawa spesifik pada ekstrak Gonystylus bancanus yang memiliki kemampuan menghambat replikasi DENV-2 maupun fase replikasi DENV-2 yang dihambat.
ABSTRAK
Dengue Virus DENV infection remains a global health problem. Since the high infection rate without any specific vaccine or antiviral yet increase the mortality risk. Gonystylus bancanus plant which widely available in Indonesia having analgesic, antialergic, antiiinflamatory, antibacterial, and antiviral property. This research aims to investigate the leaf extract of Gonystylus bancanus in inhibiting DENV serotipe 2 DENV 2 replication using Huh 7.5 cells infected by DENV 2 with multiplicity of infection m.o.i 0.5 in vitro. Sample of this research consist of DENV 2 infected cell culture as positive control and the treatment groups of Gonystylus bancanus leaf extract given in 20 g mL,10 g mL, 5 g mL, 2,5 g mL, and 1,25 g mL concentration. Antiviral activity was examined based on foci forming unit using immunostaining method. The statistic analysis shows that various concentrations of given Gonystylus bancanus natural extract are significantly inhibit the DENV 2 replication p 0,05 . Inhibitory activity towards the DENV 2 are directly proportional to the concentration of given Gonystylus bancanus leaf extract with maximum inhibition activity in 20 g mL concentration which able to inhibit 46,10 of the viral replication. Further research could be conducted to investigate the specific compounds of Gonystylus bancanus extract which inhibit the DENV 2 replication and the specific replication phase of DENV 2 inhibited by it.
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2016
S70333
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