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Aktivitas Antiinflamasi, Antivirus, Dan Mekanisme Penghambatan Replikasi Virus Dengue Dari Propil Galat Dan Etil Galat Secara In Vitro Dan In Silico = Anti-inflammatory, Antiviral Activity And Inhibition Mechanisms Of Dengue Virus Replication By Propyl Gallate And Ethyl Gallate: In Vitro And In Silico Studies

Lovendo Ilham Widodo; Beti Ernawati Dewi, supervisor; Fithriyah, supervisor; Febrina Catur Iswanti, examiner; Ade Arsianti, examiner; Bimo Ario Tejo, examiner (Fakultas Kedokteran Universitas Indonesia, 2023)

 Abstract

Infeksi virus dengue (DENV) merupakan salah satu masalah kesehatan global yang belum dapat diatasi. IFN-γ merupakan respon imun yang berperan dalam mekanisme antivirus yang juga dapat memicu reaksi inflamasi dalam perjalanan infeksi DENV. Berdasarkan hasil penelitian sebelumnya, diketahui propil galat dan etil galat memiliki kemampuan anti DENV, yang dalam penelitian ini dianalisis lebih lanjut mekanismenya dalam menghambat replikasi DENV dengan sistem kultur sel Vero, potensi antiinflamasi melalui pembentukan spot sel PBMC penghasil IFN-γ dengan sistem ADE, serta analisis ADMETox dan molecular docking yang menargetkan propil galat dan etil galat terhadap protein DENV secara in-silico. Propil galat dan etil galat terbukti memiliki aktivitas antiDENV tertinggi pada tahap pasca-infeksi, 94,04 ± 1,75% (propil galat) dan 92,07 ± 2,20% (etil galat). Pemberian propil galat dan etil galat juga terbukti dapat menurunkan jumlah SFU IFN-γ pada PBMC yang diinfeksikan DENV, 366,83±6,03 (propil galat 2xIC50), 315,75±4.99 (etil galat 2xIC50). Hasil studi ADMETox kedua antivirus ini memenuhi 5 kaidah aturan Lipisnki dan tidak bersifat toksik. Sementara itu, docking terhadap protein E, NS1, dan NS3 menghasilkan nilai energi ikatan terbesar pada protein NS3. Propil galat dan etil galat mempunyai potensi untuk dikembangkan sebagai kandidat obat untuk infeksi DENV.

Dengue virus infection (DENV) is one of the global health problems that has yet to be solved. In the course of DENV infection, IFN-γ is an immune response that plays a role in antiviral mechanisms that can also trigger inflammatory reactions. From the results of previous studies, it is known that propyl gallate and ethyl gallate have anti-DENV abilities. This study are further analyzed for their mechanisms in inhibiting DENV replication with the Vero cell culture system, anti-inflammatory potential through the formation of IFN-γ-producing PBMC cell spots with the ADE system, and analysis ADMETox of propyl gallate and ethyl gallate and binding targets evaluation to DENV proteins through in-silico analysis. Propyl gallate and ethyl gallate were shown to have the highest antiDENV activity at the post-infection stage, 94.04 ± 1.75% (propyl gallate) and 92.07 ± 2.20% (ethyl gallate). Administration of propyl gallate and ethyl gallate was also shown to reduce the number of SFU IFN-γ in DENV-infected PBMCs, 366.83 ± 6.03 (propyl gallate 2xIC50), 315.75 ± 4.99 (ethyl gallate 2xIC50). The results of the ADMETox study of these two antivirals fulfill the 5 rules of Lipisnki's rule and are not toxic. Meanwhile, docking against E, NS1, and NS3 proteins resulted in the largest binding energy value on the NS3 protein. Propyl gallate and ethyl gallate have the potential to be developed as drug candidates for DENV infection.

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Collection Type : UI - Tesis Membership
Call Number : T-pdf
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Publishing : Jakarta: Fakultas Kedokteran Universitas Indonesia, 2023
Cataloguing Source LibUI ind rda
Content Type text
Media Type computer
Carrier Type online resource
Physical Description xvii, 96 pages : illustration + appendix
Concise Text
Holding Institution Universitas Indonesia
Location Perpustakaan UI
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Call Number Barcode Number Availability
T-pdf 15-23-72886855 TERSEDIA
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No review available for this collection: 9999920519011
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