In-silico investigation of oxoaporphine alkaloids of Xylopia aethiopica against SARS-COV-2 main protease (original) (raw)
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SDRP Journal of Computational Chemistry & Molecular Modeling, 2021
Year 2020 has been highly affected by the COVID-19 outbreak. The urgent need for a potent and effective drug for the treatment of this malignancy put pressure on researchers and scientists worldwide to develop a potential drug or a vaccine to resist SARS-CoV-2 virus. We report in this paper the assessment of the efficiency of thirty alkaloid compounds derived from African medicinal plants against the SARS-CoV-2 main protease through molecular docking and bioinformatics approaches. The results revealed four potential inhibitors (ligands 18, 21, 23 and 24) with 12.26 kcal/mol being the highest binding energy. Additionally, in silico drug-likeness and ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) properties for the four ligands showed a good predicted therapeutic profile of druggability, and fully obey the Lipinski's rule of five as well.
Journal of Advanced Biotechnology and Experimental Therapeutics, 2020
ABSTRACT: Coronaviruses are endemic in humans and infections typically mild, such as the common cold. Still, the cross-species transmission has produced some unusually virulent strains which now causing viral pneumonia, in severe cases, even acute respiratory distress syndrome and death. SARS-CoV-2 is the most threatening issue which leads the world to an uncertainty alongside thousands of regular death scenes. An effective vaccine to cure this virus is not yet available, so it requires concerted efforts at various scales. The viral Main Protease controls coronavirus replication and is a proven drug discovery target for SARS-CoV-2. Comprehensive computational study e.g., molecular docking and ADMET (absorption, distribution, metabolism and excretion) profiling were employed to predict the efficacy of medicinal plant-based bioactive compounds against SARS-CoV-2 MPP. Paritaprevir and lopinavir-previously approved viral main protease inhibitors were used as standards for comparison. MPP was docked with 90 phytochemical compounds, and the screening revealed that four compounds (azadirachtin,-12.5 kcal/mol; rutin,-9 kcal/mol; theaflavin,-9 kcal/mol; astragalin,-8.8 kcal/mol) showed the highest binding affinity than the controls paritaprevir and lopinavir (-8.7 and-7.9 kcal/mol, respectively). Comparative structural analysis of protein-inhibitor complexes revealed that the compounds have intense interaction with the vital catalytic residue His-41 and Cys-145. Furthermore, the pharmaco-kinetics and drug-likeness properties of the antiviral phytochemicals suggested that the compounds do not have any considerable detrimental effects and can be considered potential drug candidates against SARS-CoV-2. These compounds can be further explored for in vitro experimental validation against SARS-CoV-2.
Coronaviruses are endemic in humans and infections normally mild, such as the common cold but cross-species transmission has produced some unusually virulent strains which now causing viral pneumonia and in serious cases even acute respiratory distress syndrome and death. SARS-CoV-2 is the most threatening issue which leads the world to an uncertainty alongside thousands of regular death scenes. For this virus, death toll is increasing in. An effective vaccine to cure this virus is not yet available, thus requires concerted efforts at various scales. The viral Main Protease controls Coronavirus replication and is a proven drug discovery target for SARS-CoV-2. Here, comprehensive computational approaches including drug repurposing and molecular docking were employed to predict the efficacy of medicinal plant-based bioactive compounds against SARS-CoV-2 Mpro. Molecular docking was performed using PyRx-autodock vina to analyze the inhibition probability. MPP (6LU7) was docked with 90 p...
Molecular Docking Analysis of Some Phytochemicals on Two Sars-Cov-2 Targets
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (previously called 2019 novel coronavirus (2019-nCoV) is the causative agent of coronavirus disease 2019 (COVID-19), a disease recently declared a global public health emergency by the World Health Organization. At the moment there is no available drug(s) and vaccine(s) for the treatment or prevention of COVID-19. SARS-CoV-2 spike envelope glycoprotein (S) and main protease (Mpro) are crucial determinants in the virus infectious process and have been recognized as key targets for therapeutics designs. In the present in silico study, a library of 22 phytochemicals with antiviral activity obtained from PubChem Database was screened for activity against 6lu7 and 6vsb with the PyRX software. Six lead compounds with binding energies within the range of −9 to −9.6 Kcal/mol were selected for molecular docking analyses against 6lu7. SwissADMET and Molinspiration Cheminformatics for CLogP (mean range of 0.77-8.72) of the lead compo...
Scientifica
Since the outbreak of the COVID-19 (coronavirus disease 19) pandemic, researchers have been trying to investigate several active compounds found in plants that have the potential to inhibit the proliferation of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). The present study aimed to evaluate bioactive compounds found in plants using a molecular docking approach to inhibit the main protease (Mpro) and spike (S) glycoprotein of SARS-CoV-2. The evaluation was performed on the docking scores calculated using AutoDock Vina (AV) as a docking engine. A rule of five (Ro5) was calculated to determine whether a compound meets the criteria as an active drug orally in humans. The determination of the docking score was performed by selecting the best conformation of the protein-ligand complex that had the highest affinity (most negative Gibbs’ free energy of binding/ Δ G ). As a comparison, nelfinavir (an antiretroviral drug), chloroquine, and hydroxychloroquine sulfate (antimala...
Molecular docking analysis of selected phytochemicals on two SARS-CoV-2 targets
F1000Research
Background: The coronavirus spike (S) glycoprotein and M protease are two key targets that have been identified for vaccines and drug development against COVID-19. Methods: Virtual screening of some compounds of plant origin that have shown antiviral activities were carried out on the two targets, the M protease (PDB ID 6LU7) and S glycoprotein (PDB ID 6VSB), by docking with PyRx software. The binding affinities were compared with other compounds and drugs already identified as potential ligands for the M protease and S glycoprotein, as well as chloroquine and hydroxychloroquine. The docked compounds with best binding affinities were also filtered for drug likeness using the SwissADME and PROTOX platforms on the basis of physicochemical properties and toxicity, respectively. Results: The docking results revealed that scopadulcic acid and dammarenolic acid had the best binding affinity for the S glycoprotein and Mpro protein targets, respectively. Silybinin, through molecular docking...
In silico analysis of selected alkaloids against main protease (Mpro) of SARS-CoV-2
Chemico-Biological Interactions, 2020
In the present situation, COVID-19 has become the global health concern due to its high contagious nature. It initially appeared in December 2019 in Wuhan, China and now affected more than 190 countries. As of now preventive measures are the sole solution to stop this disease for further transmission from person to person transmissions as there is no effective treatment or vaccine available to date. Research and development of new molecule is a laborious process; therefore, drug repurposing can be an alternative solution that involves the identification of potential compounds from the already available data. Alkaloids are potential source of therapeutic agents which might be able to treat novel COVID-19. Therefore, in the present study, twenty potential alkaloid molecules that possess antiviral activity against different viral diseases have taken into consideration and scrutinized using Lipinski's rule. Then out of twenty compounds seventeen were further selected for docking study. Docking study was performed using Autodock software and the best four molecule which provides maximum negative binding energy was selected for further analysis. Two alkaloids namely thalimonine and sophaline D showed potential activity to inhibit the M pro but to confirm the claim further in-vitro studies are required.
Chemistry Africa
At the end of 2019, the world faced a big challenge and crisis caused by the SARS-CoV-2 virus. It spreads rapidly and is contagious; no treatment has officially been found. Algeria has used medicinal plants native to the country to defend against this pandemic. The objective of this paper is based on a molecular docking study of the active compounds of five Algerian medicinal plants with their target Sars-2Cov-2 virus protease to assess their potential antiviral activity against COVID-19. Innovative software and computerized databases were introduced into the in-silico domain, mainly the Auto-Dock software version 1.5.6. Similar results were obtained for all ligands, with a better chemical affinity of − 5.600 kcal/mol for the protease target 6LU7 and − 5.700 kcal/mol for the protease target 6WTT, with an average of − 4.227 kcal/mol and − 4.221 kcal/mol, respectively. The protease targets 6LU7 and 6WTT. In the ADME-Tox study, the active compounds of Algerian medicinal plants also demonstrated an excellent pharmacokinetic and toxic profile. Best scores were noted for cedrol, camphor, and eucalyptol. A molecular dynamics simulation showed the stability of camphor-6LU7 and cedrol-6LU7 complexes, favoring the biological potential of white artemisia and cypress plants.
Phyton
Coronaviruses caused an outbreak pandemic disease characterized by a severe acute respiratory distress syndrome leading to the infection of more than 200 million patients and the death of more than 4 million individuals. The primary treatment is either supportive or symptomatic. Natural products have an important role in the development of various drugs. Thus, screening of natural compounds with reported antiviral activities can lead to the discovery of potential inhibitory entities against coronaviruses. In the current study, an in-silico molecular docking experiment was conducted on the effects of some of these natural antiviral phytoconstituents, (e.g., procyanidin B2, theaflavin, quercetin, ellagic acid, caffeoylquinic acid derivatives, berginin, eudesm-1β, 6α, 11-triol and arbutin), on the crystal structure of SARS-CoV-2 main protease (PDB ID: 6w63) using AutoDock-Vina software. Many of the docked compounds revealed good binding affinity, with procyanidin B2 (-8.6 Kcal/mol) and theaflavin (-8.5 Kcal/mol) showing a better or similar binding score as the ligand (-8.5 Kcal/mol). Molecular dynamics simulations were carried out at 100 ns and revealed that procyanidin B2 forms a more stable complex with SARS-CoV-2 main protease than theaflavin. Procyanidin B2, theaflavin, and 4,5-dicaffeoylquinic acid were evaluated for toxicity by ProTox-II webserver and were non-toxic according to the predicted LD50 values and safe on different organs and pathways. Additionally, these phytoconstituents showed good ADME properties and acceptable lipophilicity, as evaluated using WLOGP. Amongst the tested compounds, procyanidin B2 showed the highest lipophilic value. It is worth mentioning that these natural inhibitiors of SARS-CoV-2 main protease are components of green and black tea that can be used as a supporting supplement for COVID patients or as potential nuclei for further drug design and development campaigns. KEYWORDS Coronavirus; natural products; SARS-CoV-2 main protease; molecular docking; molecular dynamics; tea This work is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
2020
Since the outbreak of the COVID-19 (coronavirus disease 19) pandemic, researchers have been trying to investigate several active compounds found in plants that have the potential to inhibit the proliferation of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). e present study aimed to evaluate bioactive compounds found in plants using a molecular docking approach to inhibit the main protease (M pro) and spike (S) glycoprotein of SARS-CoV-2. e evaluation was performed on the docking scores calculated using AutoDock Vina (AV) as a docking engine. A rule of five (Ro5) was calculated to determine whether a compound meets the criteria as an active drug orally in humans. e determination of the docking score was performed by selecting the best conformation of the protein-ligand complex that had the highest affinity (most negative Gibbs' free energy of binding/ΔG). As a comparison, nelfinavir (an antiretroviral drug), chloroquine, and hydroxychloroquine sulfate (antimalarial drugs recommended by the FDA as emergency drugs) were used. e results showed that hesperidin, nabiximols, pectolinarin, epigallocatechin gallate, and rhoifolin had better poses than nelfinavir, chloroquine, and hydroxychloroquine sulfate as spike glycoprotein inhibitors. Hesperidin, rhoifolin, pectolinarin, and nabiximols had about the same pose as nelfinavir but were better than chloroquine and hydroxychloroquine sulfate as M pro inhibitors. is finding implied that several natural compounds of plants evaluated in this study showed better binding free energy compared to nelfinavir, chloroquine, and hydroxychloroquine sulfate, which so far are recommended in the treatment of COVID-19. From quantum chemical DFT calculations, the ascending order of chemical reactivity of selected compounds was pectolinarin > hesperidin > rhoifolin > morin > epigallocatechin gallate. All isolated compounds' C�O regions are preferable for an electrophilic attack, and O-H regions are suitable for a nucleophilic attack. Furthermore, Homo-Lumo and global descriptor values indicated a satisfactory remarkable profile for the selected compounds. As judged by the RO5 and previous study by others, the compounds kaempferol, herbacetin, eugenol, and 6-shogaol have good oral bioavailability, so they are also seen as promising candidates for the development of drugs to treat infections caused by SARS-CoV-2. e present study identified plant-based compounds that can be further investigated in vitro and in vivo as lead compounds against SARS-CoV-2.