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Indonesian Journal of Medical Chemistry and Bioinformatics

Abstract

Background: There are still no specific treatments for coronavirus disease (COVID-19) until present days. Several studies have been conducted to determine whether herbal medicine can be an option to be used as a definitive medicine for COVID-19. S2 subunit of spike protein which is responsible for SARS-CoV-2 entry to the host cell, is a potential drug target to inhibit the viral infection. In this study, we aimed to find some compounds from the HerbalDB database that have potential as SARS-CoV-2 spike (S2) glycoprotein inhibitor.

Methods: The 6LXT protein was used as the target protein. The procedure in this study consisted of these following steps: protein and ligand preparation, pharmacophore modelling and compound screening, molecular docking, ADME, and toxicity analysis. The docking of hit compounds to the target protein were compared to arbidol and quercetin as positive controls.

Results: Four hit compounds were screened from HerbalDB compounds. Two of them, octopamine and L-noradrenaline, showed lower binding energies (respectively, -5.19 and -4.98 kcal/mol) than positive controls whereas the other two compounds, mimosine and L-theanine, showed higher binding energies (respectively, -3.99 and -3.62 kcal/mol) compared to positive controls. Mimosine, L-noradrenaline, octopamine, and L-theanine had toxicity classes of IV, II, IV, and IV, respectively.

Conclusion: Octopamine shows the best potential as SARS-CoV-2 spike (S2) glycoprotein inhibitor. However, this compound also poses several toxicity risks and therefore, needs a more elaborate considera-tion upon using.

There are still no specific treatments for coronavirus disease (COVID-19) until present days. Several studies have been conducted to determine whether herbal medicine can be an option to be used as a definitive medicine for COVID-19. S2 subunit of spike protein which is responsible for SARS-CoV-2 entry to the host cell, is a potential drug target to inhibit the viral infection. In this study, we aimed to find some compounds from the HerbalDB database that have potential as SARS-CoV-2 spike (S2) glycoprotein inhibitor.

Bahasa Abstract

Latar belakang: Hingga saat ini masih belum ada pengobatan khusus untuk COVID-19. Beberapa penelitian telah dilakukan untuk mengetahui apakah obat herbal dapat menjadi pilihan untuk digunakan sebagai obat definitif untuk COVID-19. Subunit S2 dari protein spike yang bertanggung jawab atas masuknya SARS-CoV-2 ke sel inang, merupakan target obat yang potensial untuk menghambat infeksi virus. Dalam penelitian ini, kami bertujuan untuk menemukan beberapa senyawa dari database HerbalDB yang berpotensi sebagai inhibitor glikoprotein spike (S2) SARS-CoV-2.

Metode: Protein 6LXT digunakan sebagai protein target. Prosedur dalam penelitian ini terdiri dari langkah-langkah berikut: preparasi protein dan ligan, pemodelan farmakofor dan skrining senyawa, molecular docking, ADME, dan analisis toksisitas. Docking senyawa hit ke protein target dibandingkan dengan arbidol dan quercetin sebagai kontrol positif.

Hasil: Empat senyawa hit disaring dari senyawa HerbalDB. Dua di antaranya, octopamine dan L-noradrenaline, menunjukkan energi ikat yang lebih rendah (masing-masing, -5,19 dan -4,98 kkal/mol) dibandingkan kontrol positif sedangkan dua senyawa lainnya, mimosine dan L-theanine, menunjukkan energi ikat yang lebih tinggi (masing-masing, -3,99 dan -3,62 kkal/mol) dibandingkan dengan kontrol positif. Mimosine, L-noradrenaline, octopamine, dan L-theanine masing-masing memiliki kelas toksisitas IV, II, IV, dan IV.

Kesimpulan: Octopamine menunjukkan potensi terbaik sebagai inhibitor glikoprotein spike (S2) SARS-CoV-2. Namun, senyawa ini juga menimbulkan beberapa risiko toksisitas. Oleh karena itu, perlu pertimbangan yang lebih terperinci saat digunakan.

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