Malaysian Journal of Analytical Sciences, Vol 27 No 6 (2023): 1300 - 1325

 

ANTIVIRAL STUDY OF SCHIFF BASE VANILLIN DERIVATIVES AGAINST NS2B-NS3 PROTEASE OF ZIKA VIRUS BASED ON PHARMACOPHORE MODELLING AND MOLECULAR DOCKING

 

(Kajian Antiviral Terbitan Vanillin Bes-Schiff Terhadap NS2B-NS3 Protease Virus Zika Berdasarkan Pemodelan Farmakofor dan Dok Molekul)

 

Woon Yi Law*, Mohd Razip Asaruddin, and Showkat Ahmad Bhawani

 

Faculty of Resource Science and Technology,

Universiti Malaysia Sarawak, 94300 Kota Samarahan, Sarawak, Malaysia

 

*Corresponding author: mendah_wylaw@hotmail.com

 

 

Received: 20 June 2023; Accepted: 24 October 2023; Published:  29 December 2023

 

 

Abstract

The Zika virus (ZIKV) is a mosquito-borne virus spread by the bite of Aedes aegypti and Aedes albopictus mosquitoes. The outbreak of the virus resulted in the 2015-2016 ZIKV epidemic, in which later Public Health Emergency of International Concern was declared by the World Health Organization (WHO). Despite the complications following the infection of ZIKV, clinically approved therapeutic agents and vaccines are still unavailable for the treatment of ZIKV. Schiff base vanillin derivatives, derived from vanillin and primary amines, were reported for their potential antiviral activity against a several viruses, including influenza virus and SARS coronaviruses. Therefore, they were aimed to be tested for their in silico antiviral activity against ZIKV NS2B-NS3 protease. In this research, ligand-based pharmacophore modelling was employed to analyse the antiviral activity of Schiff base vanillin derivatives. They were imported as test sets in the pharmacophore model generated from a list of training sets, which are reported drugs against ZIKV. Furthermore, structure-based molecular docking was also performed to analyse the docking performances of the Schiff base vanillin derivatives in the crystal structure of ZIKV NS2B-NS3 protease in a complex with a boronate inhibitor (PDB: 5LC0). The analyses were based on pharmacophore scores, binding affinities and matching interactions in comparison with the 5LC0 ligand in the active site. Based on the findings via ligand-based pharmacophore modelling and structure-based molecular docking, it was discovered that a number of Schiff base vanillin derivatives showed potential antiviral activity against ZIKV, thus being promising drug candidates and bringing futuristic in vitro and in vivo tests.

 

Keywords: Zika virus, Schiff base vanillin derivatives, pharmacophore modelling, molecular docking, computer-aided drug design

 

Abstrak

Virus Zika (ZIKV) adalah virus bawaan nyamuk yang disebarkan melalui gigitan nyamuk Aedes aegypti dan Aedes albopictus. Wabak virus ini menyebabkan epidemik ZIKV 2015-2016, di mana kemudian Darurat Kesihatan Awam Keprihatinan Antarabangsa telah diisytiharkan oleh Pertubuhan Kesihatan Sedunia (WHO). Walaupun komplikasi setelah jangkitan ZIKV, agen terapeutik dan vaksin yang diluluskan secara klinikal masih belum tersedia untuk rawatan ZIKV. Terbitan vanillin bes-Schiff, yang diperolehi daripada vanilin dan amina primer, telah dilaporkan aktiviti antiviral berpotensi terhadap beberapa virus, termasuk virus influenza dan koronavirus SARS. Oleh itu, mereka akan diuji untuk aktiviti antiviral secara in silico terhadap protease NS2B-NS3 ZIKV. Dalam penyelidikan ini, pemodelan farmakofor berasaskan ligan digunakan untuk menganalisis aktiviti antiviral terbitan vanillin bes-Schiff. Mereka diimport sebagai set ujian terhadap model farmakofor yang dihasilkan daripada senarai set latihan, iaitu ubat-ubatan dilaporkan terhadap ZIKV. Selain itu, dok molekul berasaskan struktur juga dilakukan untuk menganalisis prestasi dok terbitan vanillin bes-Schiff di dalam struktur kristal ZIKV NS2B-NS3 protease dalam kompleks dengan perencat boronat (PDB: 5LC0). Analisis dijalankan berdasarkan skor farmakofor, afiniti dok, dan interaksi yang sepadan dengan ligan 5LC0 di tapak aktif. Berdasarkan hasil pemodelan farmakofor berasaskan ligan dan dok molekul berasaskan struktur, adalah didapati bahawa beberapa terbitan vanillin bes-Schiff menunjukkan aktiviti antiviral yang berpotensi terhadap ZIKV, oleh itu menjadi calon ubat yang menjanjikan dan mampu membawa ujian in vitro dan in vivo pada masa depan.

 

Kata kunci: Virus Zika, terbitan vanillin bes-Schiff, pemodelan farmakofor, dok molekul, reka bentuk ubat bantuan komputerTop of Form

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