Exploring the inhibitory potential of Saussurea costus and Saussurea involucrata phytoconstituents against the Spike glycoprotein receptor binding domain of SARS-CoV-2 Delta (B.1.617.2) variant and the main protease (Mpro) as therapeutic candidates, using Molecular docking, DFT, and ADME/Tox studies

Houchi, Selma; Messasma, Zakia

doi:10.1016/j.molstruc.2022.133032

Cited by 18 publications

(11 citation statements)

References 110 publications

(126 reference statements)

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“…The formation of hydrogen bonds is an important factor influencing the integrity and stability of any protein‐ligand interaction. [ 18 ] Conventional hydrogen bonds are the only common interactions found between complexes 1 and 2 and the active sites of the spike proteins of the investigated variants. The average hydrogen bond distances between complex 1 and with Leu514, Asp425, and Glu513 amino acids of 7V76; Ans81, Arg237, Gln239, Asn137, and Thr22 amino acids of 7V78; Gly28 and Arg44 amino acids of 7V7N; Thr51, Lys202, Pro39, Asp53, and Asp228 amino acids of 7V7D; and His1058, Asp867, and Val952 amino acids of 7T9J were found as 2.14, 2.34, 2.58, 2.68, and 2.60 Å, respectively.…”

Section: Resultsmentioning

confidence: 99%

“…[ 17 ] Scientists are struggling to create anti‐CoV2 drugs and vaccines specific to SARS‐CoV‐2 due to the high rate of mutation and recombination. [ 18 ] Therefore, it is important to know the effects of drug candidate compounds on various variants. Although some metal arylcarboxylate complexes exhibit antiviral properties against some viruses, studies on the drug potential of SARS CoV‐2 were limited.…”

Section: Introductionmentioning

confidence: 99%

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Pyridine derivatives complexes of Co(II) and Ni(II) 3‐bromobenzoates: Crystal structure, in silico anti‐SARS‐CoV‐2 potential, serum albumin binding properties and cytotoxicity

Öztürkkan¹,

Özdemir²,

Akbaba³

et al. 2023

Applied Organom Chemis

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Two mononuclear [Co(3‐BrBA)2(NA)2(H2O)2] (1) and [Ni(3‐BrBA)2(3‐CNPY)2(H2O)2] (2) (3‐BrBA = 3‐bromobenzoate, NA = pyridine‐3‐carboxylic acid, and 3‐CNPy = 3‐cyanopyridine) were synthesized and characterized by single crystal X‐ray diffraction, elemental analysis, and FT‐IR spectroscopy. In both complexes, the metal atom is coordinated by two oxygen atoms of two carboxylate anions, two nitrogen atoms of two pyridine rings, and two oxygen atoms of two water molecules in the distorted octahedral environment. Intermolecular interactions were examined with the help of the 3D Hirshfeld surfaces and 2D fingerprint plots. With the help of density functional theory (DFT) studies, besides verifying the experimentally obtained structural properties, the electronic energies, polarizability, dipole moments, ionization potentials, electron affinities, electronegativity, chemical hardness, global softness, electrophilic indexes, HOMO‐LUMO orbitals, and band gaps were also calculated. In vitro cytotoxic activity of the complexes on primary peripheral blood mononuclear cells were evaluated using the MTT assay. Fluorescence quenching techniques and molecular docking studies were used to investigate the interaction between bovine serum albumin (BSA) and the complexes. The molecular docking study has been used to explain the interaction of complexes with spike proteins of beta variant (B.1.351), gamma variant (P.1), delta variant (B.1.617.2), kappa variant (B.1.617.1), and omicron variant (B.1.1.529) of coronavirus. Additionally, the pharmacokinetic and toxicological properties of the complexes have been computed using the SwissADME and ProTox‐II online databases, respectively.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pyridine derivatives complexes of Co(II) and Ni(II) 3‐bromobenzoates: Crystal structure, in silico anti‐SARS‐CoV‐2 potential, serum albumin binding properties and cytotoxicity

Öztürkkan¹,

Özdemir²,

Akbaba³

et al. 2023

Applied Organom Chemis

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“…S. costus has been approved as a potential antiviral drug candidate against the B.1.617.2 Delta variant of SARS-CoV2. It contains bioactive compounds that act as viral protease inhibitors [17]. Additionally, its biological activities are widely studied and showed that it contains anti-trypanosomal activities [18].…”

Section: Resultsmentioning

confidence: 99%

Extraction and Evaluation of Active Ingredients of Saussurea costus Roots and Determination of its Antibacterial Activity

Al-Zayadi,

Shanan,

Salihi

2023

IOP Conf. Ser.: Earth Environ. Sci.

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Saussurea costus (Sc) plant belongs to the Asteraceae family. It contains various bioactive compounds used traditionally in treating multiple diseases. This study intends to extract and evaluate the active ingredients of Sc roots (Scrs) and determine their antibacterial activities. S. costus roots were purchased from the herbal market and the chemical compositions, including protein, lipid, carbohydrates, moisture, and ash, were determined according to AOAC procedures 2016 with some modifications. HPLC and amino acids analyzer were used to determine the phenolic compounds and amino acid composition of S. costus roots extract (ScrsE). The antibacterial activities of S. costus roots extract were done according to the Kirby-Bauer disc diffusion method. The S. costus roots were revealed a fusiform (or) conical and tapering appearance, collapsing in the centre with longitudinal wrinkles revealing 11-19 cm and 1-2.5 cm for long and wide, respectively. The extraction yield was 9.52% and the weight of the concentrated crude extract was 10 g. According to Proximate analysis, the S. costus roots extract showed 3.88% and 20.12% moisture and ash contents, respectively. The compositions of carbohydrates, protein, and crude fat were 75.25%, 2.51%, and 1.85%, respectively. HPLC analysis showed that the S. costus roots Extract contained two phenolic acids and two flavonoids. Moreover, twelve amino acids were determined for the first time in the S. costus roots extract. Various antibacterial activities were seen with maximum inhibition zone for Streptococcus pyogenes & E.coli; and minimum for Bacillus subtilis & Pseudomonas aeruginosa. In conclusion, this study investigated various contents of S. costus roots extract including amino acids, carbohydrates, protein, and crude fat, in addition to its antibacterial activities. The authors recommend more future studies to investigate the therapeutic activities of S. costus roots extract.

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“…Perhaps the most common misinterpretation of computational studies related to SARS-CoV-2 is taking molecular docking results as a demonstration of ligand binding . Examples of this can be found in the scientific literature, particularly in reports where a few plant-derived compounds are docked into the Mpro and/or PLpro enzymes, and authors claimed that the top-scoring ones are enzyme inhibitors. ,− We understand that not all research groups have the capability of experimentally testing their predictions. However, some theoretical options could add additional support to computational studies, making them attractive for groups who do have the capacity for performing experimental evaluations.…”

Section: Resultsmentioning

confidence: 99%

Critical Review of Plant-Derived Compounds as Possible Inhibitors of SARS-CoV-2 Proteases: A Comparison with Experimentally Validated Molecules

et al. 2022

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Ever since coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, was declared a pandemic on March 11, 2020, by the WHO, a concerted effort has been made to find compounds capable of acting on the virus and preventing its replication. In this context, researchers have refocused part of their attention on certain natural compounds that have shown promising effects on the virus. Considering the importance of this topic in the current context, this study aimed to present a critical review and analysis of the main reports of plant-derived compounds as possible inhibitors of the two SARS-CoV-2 proteases: main protease (Mpro) and Papain-like protease (PLpro). From the search in the PubMed database, a total of 165 published articles were found that met the search patterns. A total of 590 unique molecules were identified from a total of 122 articles as potential protease inhibitors. At the same time, 114 molecules reported as natural products and with annotation of theoretical support and antiviral effects were extracted from the COVID-19 Help database. After combining the molecules extracted from articles and those obtained from the database, we identified 648 unique molecules predicted as potential inhibitors of Mpro and/or PLpro. According to our results, several of the predicted compounds with higher theoretical confidence are present in many plants used in traditional medicine and even food, such as flavonoids, carboxylic acids, phenolic acids, triterpenes, terpenes phytosterols, and triterpenoids. These are potential inhibitors of Mpro and PLpro. Although the predictions of several molecules against SARS-CoV-2 are promising, little experimental information was found regarding certain families of compounds. Only 45 out of the 648 unique molecules have experimental data validating them as inhibitors of Mpro or PLpro, with the most frequent scaffold present in these 45 compounds being the flavone. The novelty of this work lies in the analysis of the structural diversity of the chemical space among the molecules predicted as inhibitors of SARS-CoV-2 Mpro and PLpro proteases and the comparison to those molecules experimentally validated. This work emphasizes the need for experimental validation of certain families of compounds, preferentially combining classical enzymatic assays with interaction-based methods. Furthermore, we recommend checking the presence of Pan-Assay Interference Compounds (PAINS) and the presence of molecules previously reported as inhibitors of Mpro or PLpro to optimize resources and time in the discovery of new SARS-CoV-2 antivirals from plant-derived molecules.

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Exploring the inhibitory potential of Saussurea costus and Saussurea involucrata phytoconstituents against the Spike glycoprotein receptor binding domain of SARS-CoV-2 Delta (B.1.617.2) variant and the main protease (Mpro) as therapeutic candidates, using Molecular docking, DFT, and ADME/Tox studies

Cited by 18 publications

References 110 publications

Pyridine derivatives complexes of Co(II) and Ni(II) 3‐bromobenzoates: Crystal structure, in silico anti‐SARS‐CoV‐2 potential, serum albumin binding properties and cytotoxicity

Pyridine derivatives complexes of Co(II) and Ni(II) 3‐bromobenzoates: Crystal structure, in silico anti‐SARS‐CoV‐2 potential, serum albumin binding properties and cytotoxicity

Extraction and Evaluation of Active Ingredients of Saussurea costus Roots and Determination of its Antibacterial Activity

Critical Review of Plant-Derived Compounds as Possible Inhibitors of SARS-CoV-2 Proteases: A Comparison with Experimentally Validated Molecules

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