Potential of plant alkaloids as dengue ns3 protease inhibitors: Molecular docking and simulation approach

Muhammad Tahir Ul Qamar,Muhammad Muzammal Adeel,Arooj Mumtaz,Tabeer Fatima,Usman Ali Ashfaq

doi:10.3329/bjp.v9i3.18555

Muhammad Tahir Ul Qamar, Muhammad Muzammal Adeel + Show 3 more

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https://doi.org/10.3329/bjp.v9i3.18555

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Abstract

Dengue infection has become a worldwide health problem and infection rate is increasing each year. Alkaloids are important phytochemicals of medicinal plant and can be used as vaccine candidates for viruses. Therefore, present study was designed to find potential alkaloids inhibitors against the Dengue virus NS2B/NS3 protease which can inhibit the viral replication inside the host cell. Through molecular docking it was investigated that most of the alkaloids bound deeply in the binding pocket of Dengue virus NS2B/NS3 protease and had potential interactions with catalytic triad. Five alkaloids (6-desmethylthalifaboramin; 3,5-dihydroxythalifaboramine; Betanin; Reserpic acid and Tubulosine) successfully blocked the catalytic triad of NS2B/NS3 protease and these alkaloids can serve as a potential drug candidate to stop viral replication. It can be concluded from this study that these alkaloids could serve as important inhibitors to inhibit the replication of DENV and need further in-vitro investigations to confirm their efficacy and drug ability.

Highlights

Dengue infection has become a global health problem and this appalling disease has affected almost 2.5 billion people (Idrees and Ashfaq, 2012) with an estimated 25,000 deaths per year (Hakim et al, 2011)
The 3D-structure of Dengue virus (DENV) NS2/NS3 protease was retrieved from Protein Data Bank (PDB)
All alkaloids were docked with the catalytic triad of Dengue virus NS2B/NS3 Protease

Summary

Introduction

Dengue infection has become a global health problem and this appalling disease has affected almost 2.5 billion people (Idrees and Ashfaq, 2012) with an estimated 25,000 deaths per year (Hakim et al, 2011). Recent studies have shown that more than 100 countries and about 50-100 million people are being affected with this appalling disease. The DENV genome is of 11 kb and encodes a polyprotein. This polyprotein is cleaved into 10 viral proteins including three structural and seven non-structural proteins. The order of these proteins is capsid, premembrane, envelope protein, NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5. Non-structural proteins are mainly involved in viral replication (Chambers et al, 1990)

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