Computational investigation for identification of potential phytochemicals and antiviral drugs as potential inhibitors for RNA-dependent RNA polymerase of COVID-19

Singh, Jitender; Malik, Deepti; Raina, Ashvinder

doi:10.1080/07391102.2020.1847688

Cited by 14 publications

(6 citation statements)

References 55 publications

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“…Prank Web (https://prankweb.cz/), a machine learning based method was used for the prediction of plausible binding pockets of 5-LOX protein [12]. Binding site denotes the distribution of nearby amino acid residues in active pocket and act as catalytic residues [13,14].…”

Section: Identification Of Binding Pocketmentioning

confidence: 99%

‘Mechanistic insights into 5-lipoxygenase inhibition by active principles derived from essential oils of Curcuma species: Molecular docking, ADMET analysis and molecular dynamic simulation study

et al. 2022

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Inflammation is caused by a cascade of events, one of which is the metabolism of arachidonic acid, that begins with oxidation by the enzyme 5-lipoxygenase. 5-Lipoxygenase (5-LOX) plays an important role in the inflammation process by synthesizing leukotrienes and several lipid mediators and has emerged as a possible therapeutic target for treatment of inflammatory diseases such as asthma and rheumatoid arthritis. Most of the existing 5-LOX inhibitors are synthetic and exhibit adverse side effects. In view of this, there is need to search for an alternate source of 5-LOX inhibitor with minimal side effects. The essential oil of several species of Curcuma has received considerable attention in recent times in traditional system of medicine especially for treating various inflammatory disorders. Therefore, the present study was carried out to screen the most potential 5-LOX inhibitors from essential oil components of Curcuma species and elucidate their mechanisms of action through computational biology approaches. Twenty-three phytoconstituents derived from the essential oil of Curcuma species were docked and their predictive binding energies were calculated to select the best possible ligand for 5-LOX. The top 8 ranked compounds from docking was tested for drug-likeness properties, bioactivity score, and toxicity analysis. The phytoconstituents such as α-turmerone, β-turmerone, α-terpineol and dihydrocarveolshowed the best binding affinity with 5-LOX and displayed favorable physicochemical properties. Molecular dynamics simulation in POPC lipid bilayers was carried out to understand the intrinsic dynamics and flexibility of the 5-LOX (apo) and 5-LOX-complex (α-terpineol, α-turmerone, β-turmerone and dihydrocarveol) systems. The molecular dynamic results showed that these 4 phytoconstituents interacted stably with the 5-LOX active site residues and the important bonds that were observed in the initial ligand docked compounds did not alter during the course of simulation. In general, our integrative computational approach demonstrated that the natural compounds like α-turmerone, β-turmerone, α-terpineol, and dihydrocarveol could be considered for designing specific anti-inflammatory drugs using structure-based drug design.

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Section: Identification Of Binding Pocketmentioning

confidence: 99%

‘Mechanistic insights into 5-lipoxygenase inhibition by active principles derived from essential oils of Curcuma species: Molecular docking, ADMET analysis and molecular dynamic simulation study

et al. 2022

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“…Computational approaches have been revealed to be a good strategy to test antiviral agents of SARS CoV-2 − as potential RdRp inhibitors, ,, including nucleotide analogues and chain terminators. As a result of recent notable progress in computer techniques and architectures, there has been, furthermore, a tremendous breakthrough in computational abilities.…”

Section: Introductionmentioning

confidence: 99%

Viral RNA Replication Suppression of SARS-CoV-2: Atomistic Insights into Inhibition Mechanisms of RdRp Machinery by ddhCTP

Ciardullo,

Parise,

Prejanò

et al. 2024

J. Chem. Inf. Model.

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The nonstructural protein 12, known as RNA-dependent RNA polymerase (RdRp), is essential for both replication and repair of the viral genome. The RdRp of SARS-CoV-2 has been used as a promising candidate for drug development since the inception of the COVID-19 spread. In this work, we performed an in silico investigation on the insertion of the naturally modified pyrimidine nucleobase ddhCTP into the SARS-CoV-2 RdRp active site, in a comparative analysis with the natural one (CTP). The modification in ddhCTP involves the removal of the 3′-hydroxyl group that prevents the addition of subsequent nucleotides into the nascent strand, acting as an RNA chain terminator inhibitor. Quantum mechanical investigations helped to shed light on the mechanistic source of RdRp activity on the selected nucleobases, and comprehensive all-atom simulations provided insights about the structural rearrangements occurring in the active-site region when inorganic pyrophosphate (PPi) is formed. Subsequently, the intricate pathways for the release of PPi, the catalytic product of RdRp, were investigated using Umbrella Sampling simulations. The results are in line with the available experimental data and contribute to a more comprehensive point of view on such an important viral enzyme.

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“…In recent years, the outbreaks of epidemics such as SARS and COVID-19 have heightened the necessity for the rapid screening of numerous suspected infected individuals [1][2][3][4]. Traditional manual testing methods are time-consuming, expensive, and susceptible to sample cross-contamination, underscoring the immediate requirement for efficient testing methods to address this demand [5,6].…”

Section: Introductionmentioning

confidence: 99%

Development of a New Lightweight Multi-Channel Micro-Pipette Device

Zhao,

Yuan,

Lin

et al. 2024

Machines

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In this study, to improve the efficiency of the pipetting workstation and reduce the impact of the pipetting device on the stability performance of the workstation, a novel fully automatic pipetting method is proposed. Based on this method, a lightweight, multifunctional, and quantitative twelve-channel pipetting device was designed. This device can achieve simultaneous quantitative liquid absorption for twelve channels and sequential interval liquid discharge for each channel. Initially, the overall functional requirements were determined, and with the aim of a lightweight design, the total weight of the device was controlled to be within 580 g through a reasonable structural design, material selection, and choice of driving source. The device’s overall dimensions are 170 mm × 70 mm × 180 mm (length × width × height), with a micropipetting volume ranging between 1.3 μL and 1.4 μL. Subsequently, factors affecting liquid suction stability were experimentally analyzed, and appropriate pipetting parameters were selected. The stability performance of this pipetting method during prolonged operation was investigated. Finally, the twelve-channel pipetting device was validated through experiments, demonstrating results that meet the national standards for the stability of a pipetting device. In summary, the device designed in this study exhibits novel design features, low cost, and modularity, thus demonstrating promising potential for applications in high-speed micro-volume pipetting.

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Computational investigation for identification of potential phytochemicals and antiviral drugs as potential inhibitors for RNA-dependent RNA polymerase of COVID-19

Cited by 14 publications

References 55 publications

‘Mechanistic insights into 5-lipoxygenase inhibition by active principles derived from essential oils of Curcuma species: Molecular docking, ADMET analysis and molecular dynamic simulation study

‘Mechanistic insights into 5-lipoxygenase inhibition by active principles derived from essential oils of Curcuma species: Molecular docking, ADMET analysis and molecular dynamic simulation study

Viral RNA Replication Suppression of SARS-CoV-2: Atomistic Insights into Inhibition Mechanisms of RdRp Machinery by ddhCTP

Development of a New Lightweight Multi-Channel Micro-Pipette Device

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