Aktivitas Antiviral Quercetin Terhadap Replikasi Virus Dengue Serotipe 3 (Denv-3) : Studi In Silico Pada NS5 RNA-Dependent RNA Polymerase (RdRp) Dan Uji In Vitro Pada Sel Vero

Siti Zainatun Wasilah, Prof.dr.Tri Wibawa, PhD.,Sp.MK(K.).

2026 | Disertasi | S3 Kedokteran Umum

Latar belakang:Infeksi virus dengue merupakan masalah kesehatan global, termasuk di Indonesia, dengan prevalensi tinggi dan penyebaran yang cepat. Virus dengue (DENV) terdiri atas empat serotipe, dengan DENV-3 sering dikaitkan dengan kejadian luar biasa (KLB) serta manifestasi berat seperti dengue hemorrhagic fever (DHF) dan dengue shock syndrome (DSS). Meskipun vaksin telah tersedia, efektivitasnya masih terbatas. Hingga saat ini belum terdapat antivirus spesifik untuk DBD, sehingga pengembangan kandidat obat yang efektif dan terjangkau menjadi kebutuhan mendesak. Quercetin, suatu flavonoid yang banyak ditemukan pada sayuran dan buah-buahan, dilaporkan memiliki aktivitas antivirus dengan cara menghambat enzim kunci replikasi virus, termasuk RNA-dependent RNA polymerase (RdRp).Penelitian ini bertujuan mengevaluasi aktivitas antiviral quercetin terhadap DENV-3 melalui mekanisme inhibisi RNA-dependent RNA Polymerase (RdRp) menggunakan pendekatan in silico dan in vitro.

Metode: Penelitian ini menggunakan desain pre-experimental dan exsperimental yang disusun secara bertahap. Tahap in silico dilakukan untuk memprediksi interaksi quercetin dengan RdRp DENV-3 melalui pendekatan molecular docking dan molecular dynamics, guna memperoleh informasi afinitas ikatan, stabilitas kompleks, serta potensi aktivitas inhibisi quercetin. Berdasarkan hasil tersebut, tahap in vitro dilakukan untuk memverifikasi prediksi komputasi dengan menilai efek quercetin terhadap viabilitas sel dan replikasi DENV-3. Desain yang digunakan pada uji in vitro adalah post-test only with control group, dengan sel terinfeksi DENV-3 diberi perlakuan quercetin dan dibandingkan dengan kelompok kontrol tanpa perlakuan untuk menilai pengaruh quercetin terhadap jumlah RNA DENV-3 pada kondisi pre dan post infeksi, termasuk melalui uji time-of-addition.

Hasil: Analisis in silico menunjukkan bahwa quercetin memiliki afinitas tinggi terhadap RdRp DENV-3 dengan nilai Root Mean Square Deviation(RMSD)< 2>

Kesimpulan: Quercetin berpotensi sebagai kandidat antivirus yang menarget tahap replikasi DENV-3 melalui inhibisi spesifik terhadap enzim RNA-dependent RNA polymerase (RdRp).

Background: Dengue virus infection is a global health problem, including in Indonesia, with high prevalence and rapid spread. The dengue virus (DENV) consists of four serotypes, with DENV-3 often associated with outbreaks and severe manifestations such as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Although vaccines are available, their effectiveness is still limited. To date, there is no specific antiviral for DHF, making the development of effective and affordable drug candidates an urgent need. Quercetin, a flavonoid found in vegetables and fruits, has been reported to have antiviral activity by inhibiting key viral replication enzymes, including RNA-dependent RNA polymerase (RdRp). This study aims to evaluate the antiviral activity of quercetin against DENV-3 through the inhibition of viral replication via RdRp inhibition using in silico and in vitro approaches.

Method: This study used a pre-experimental and experimental design that was arranged in stages. The in silico stage was conducted to predict the interaction of quercetin with DENV-3 RdRp using molecular docking and molecular dynamics, in order to obtain information on binding affinity, complex stability, and the potential inhibitory activity of quercetin. Based on these results, the in vitro stage was conducted to verify the computational predictions by assessing the effects of quercetin on cell viability and DENV-3 replication. The design used in the in vitro test was post-test only with a control group, in which DENV-3-infected cells were treated with quercetin and compared with an untreated control group to assess the effect of quercetin on the amount of DENV-3 RNA in pre and post-infection conditions, including through a time-of-addition test.

Results: In silico analysis shows that quercetin has a high affinity for DENV-3 RdRp with a Root Mean Square Deviation (RMSD) value < 2>

Conclusion: Quercetin has potential as an antiviral candidate that targets the replication stage of DENV-3 through specific inhibition of the RNA-dependent RNA polymerase (RdRp) enzyme.

Kata Kunci : Quercetin; RdRp; DENV-3; In Silico; In Vitro