Studi In Silico Aktivitas Analog Senyawa Zizyphine dari Bidara Arab (Zizyphus spina-christi) sebagai Antivirus SARS-CoV-2 terhadap Reseptor 3CLpro

Taufik Muhammad Fakih, Firda Aulia Jannati, Annisa Meilani, Dwi Syah Fitra Ramadhan, Fitrianti Darusman

Abstract

COVID-19 merupakan penyakit yang penularannya human to human yang pertama kali ditemukan di China (Kota Wuhan). Tanaman bidara arab mengandung banyak metabolit sekunder yang bermanfaat, hasil fraksinasi dari buah bidara memiliki aktivitas sebagai antivirus yang signifikan terhadap virus herpes simpleks tipe 1. Tujuan penelitian ini adalah untuk mengetahui afinitas dan interaksi antara senyawa uji Zizyphine dengan reseptor 3CLpro secara in silico. Pada penelitian ini dilakukan identifikasi aktivitas biologis menggunakan PASS prediction dan sifat fisikokimia pada senyawa uji Zizyphine menggunakan webserver Swiss-ADME. Senyawa uji Zizyphine dioptimasi secara geometris menggunakan software Quantum ESPRESSO versi 6.6. Konformasi senyawa uji Zizyphine terbaik dilanjutkan ke tahap simulasi docking terhadap reseptor 3CLpro yang telah dipisahkan dengan ligan alaminya dan telah divalidasi menggunakan software MGL Tools versi 1.5.6 yang telah dilengkapi dengan Autodock Tools versi 4.2. Berdasarkan penelitian yang telah dilakukan dapat disimpulkan bahwa senyawa uji Zizyphine C memiliki afinitas yang lebih baik dibandingkan senyawa Zizyphine A, Zizyphine F, dan Zizyphine I dengan nilai energi bebas ikatan sebesar -9,32 kcal/mol dan konstanta inhibisi 146,89 nM, sehingga senyawa Zizyphine C berpotensi sebagai agen terapi COVID-19 yang bekerja terhadap reseptor 3CLpro. Selanjutnya dari hasil analisis aktivitas biologis, keseluruhan senyawa analog Zizyphine menunjukkan potensi sebagai antivirus. Akan tetapi dari prediksi ADME, senyawa-senyawa tersebut tidak menunjukkan profil yang baik sebagai obat oral.

In Silico Study of Zizyphine Analog Compound Activity of Christ's Thorn Jujube (Zizyphus spina-christi) as SARS-CoV-2 Antivirus against 3CLpro Receptors. COVID-19 is a disease with human-to-human transmission that was first discovered in China (Wuhan City). The arabian bidara plant (Christ's Thorn Jujube) contains many useful secondary metabolites, fractionated from bidara fruit has significant antivirus activity against herpes simplex virus type 1. The purpose of this study was to determine the affinity and interaction between the Zizyphine test compound and the 3CLpro receptor through in silico. In this study, the identification of biological activity using PASS prediction and physicochemical properties of Zizyphine test compounds using the Swiss-ADME webserver. The Zizyphine test compound was optimized for geometry using Quantum ESPRESSO version 6.6 software. The conformation of the best Zizyphine test compound was continued to the docking simulation stage for the 3CLpro receptor which has been separated from its natural ligand and has been validated using MGL Tools version 1.5.6 with Autodock Tools version 4.2 software. Based on the results, it can be concluded that the test compound Zizyphine C has a better affinity than Zizyphine A, Zizyphine F, and Zizyphine I with a binding free energy value of -9.32 kcal/mol and inhibition constant of 146.89 nM. Therefore, the compound Zizyphine C has potential as a COVID-19 therapeutic agent that acts against the 3CLpro receptor. Furthermore, from the results of the analysis of biological activity, all Zizyphine analog compounds showed potential as antiviruses. However according to ADME predictions, these compounds did not show a good profile as oral drugs.

Keywords

3CLpro SARS-CoV-2; Zizyphine analog; COVID-19; in silico study; Ziziphus spina-christi.

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DOI: https://doi.org/10.20961/alchemy.18.1.52188.70-79

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