Molecular docking and pharmacokinetics studies of Curcuma longa (Curcumin) potency against Ebola virus

Abstract

The Ebola virus disease causing hemorrhagic fever in human, has been known for nearly about 40 years, with the most recent outbreak being in West Africa creating humanitarian crisis, where over 11,308 deaths were recorded as reported in 30th March, 2016 (World Health Organization). Till now, Ebola virus drugs have been far from achieving regulatory FDA approval, and coupled with toxicity of these drugs, it is become imperative to appraise the available trail drugs, as well as looking into alternative natural resources of tackling menace. Therefore, in silico methods were used to assess the potency of the bioactive phytochemical, Curcumin from Turmeric and results compared with those obtained for some selected trial drugs in use for the treatment of Ebola virus. This study is focused on molecular docking of Curcumin and eight commercially available drugs (Amodiaquine, Apilimod, Azithromycin, Bepridil, Pyronaridine, Remedesivir and Tilorone) against Ebola transcription activator VP30 proteins (PDB: 2I8B, 4Z9P and 5T3T) and their ADMET profiling. The results showed that binding affinity (ΔG kJ/mol) ranged from -5.8 (Tilorone) to -7.3 (Remdesivir) for 218B, -6.4 (Tilorone) to -8.2 (Pyronaridine, Remedesivir) and -5.8 (Bepridil) to -7.4 (Pyronaridine). Curcumin could be more desirable as inhibitor for than Tilorone, Dronedarone and Bepridil in the treatment of Ebola virus; the ADMET profile revealed that Curcumin presents attractive pharmacokinetic properties than the trial drugs.

Molecular properties and In silico bioactivity evaluation of (4-fluorophenyl)[5)-3-phen-(4-nitrophenyl yl-4,5-dihydro-1H-pyrazol-1-yl]methanone derivatives: DFT and molecular docking approaches

“…The docking was performed with AutoDock Tool 1.5.6 and AutoDock Vina 1.1.2; proteins were treated; and molecular interactions between receptors and ligands were visualized with Edupymol version 1.7.4.4 and BIOVIA Discovery studio 2019, as previously reported. 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 The grid box using AutoDock tool before use of AutoDock Vina for docking calculations was as follows: center (X = 4.834, Y = 15.305, Z = 24.227) and size (X = 64, Y = 52, Z = 74) for 5ADH , and (X = 32.382, Y = 72.334, Z = 31.711) and size (X = 62, Y = 58, Z = 66) for 1RO6 , with default exhaustiveness (exhaustiveness = 8) for steady docking calculation speed.…”

Curcumin as a natural potential drug candidate against important zoonotic viruses and prions: A narrative review

“…Nano‐curcumin and curcumin nano‐emulsion reduce the viral replication of DENV‐1 and DENV‐2 due to potentially enhanced cell cytotoxicity and substance absorption (Nabila et al, 2020). Acceptable docking scores of curcumin against multiple targets of EBOV such as viral proteins (VP30, VP35, VP40, and VP24) have been documented (Adepoju et al, 2022; Setlur et al, 2017). It also has shown to decrease HTNV viral RNA levels in different organs of animal model (Wei et al, 2013).…”

“…Most of the studies on the effect of curcumin and/or curcuminoids against EBOV have been performed in silico. These in silico investigations have shown that curcumin has an acceptable docking score against multiple targets of EBOV such as viral proteins (VP30, VP35, VP40, and VP45) (Adepoju et al, 2022;Baikerikar, 2017;Setlur et al, 2017). An in vitro study on male rats receiving 125 μg/kg liposomal curcumin suggested strong evidence for the role of curcumin in IL-6 and TNF-α reduction (Helson et al, 2015).…”

Virtual Screening Based on Docking and Molecular Dynamics Simulations of Potential Ebola Receptor Inhibitors

“…In year 2022, Semire et al proposed a computational study based on the antiviral activity of the phytochemicals of Curcuma longa against Ebola virus. [19] Similarly, Saeed et al, Widjaja et al, Malik et al and many more applied tools of CADD for designing antiviral against Ebola virus. [20][21][22][23] CADD is crucial in discovering new drugs against the Ebola virus (EBOV).…”

“…In year 2022, Semire et al. proposed a computational study based on the antiviral activity of the phytochemicals of Curcuma longa against Ebola virus [19] . Similarly, Saeed et al., Widjaja et al., Malik et al.…”