scholarly journals Virtual Screening of Plant-Derived Compounds Against SARS-CoV-2 Viral Proteins Using Computational Tools

2020 ◽  
Author(s):  
Maria Antonela Zigolo ◽  
Matías Rivero Goytia ◽  
Hugo Ramiro Poma ◽  
Verónica Rajal ◽  
Veronica Patricia Irazusta
Keyword(s):  
Hydrophobic Interactions ◽  
Viral Proteins ◽  
Natural Compounds ◽  
Docking Studies ◽  
Binding Energies ◽  
Host Cells ◽  
Computational Tools ◽  
S Protein ◽  
Synthetic Drugs ◽  
Main Protease

<p>The new SARS-CoV-2, responsible for the COVID-19 pandemic, has been threatening public health worldwide for half a year. The aim of this work was to evaluate compounds of natural origin, mainly from medicinal plants, as potential SARS-CoV-2 inhibitors through docking studies. The viral spike (S) glycoprotein and the main protease M<sup>pro</sup>, involved in the recognition of virus by host cells and in viral replication, respectively, were the main molecular targets in this study. </p> <p>The best energy binding values for S protein were, in kcal/mol: -19.22 for glycyrrhizin, -17.84 for gitoxin, -12.05 for dicumarol, -10.75 for diosgenin, and -8.12 for delphinidin. For M<sup>pro</sup> were, in kcal/mol: -9.36 for spirostan, -8.75 for <i>N</i>-(3-acetylglycyrrhetinoyl)-2-amino-propanol, -8.41 for α-amyrin, -8.35 for oleanane, -8.11 for taraxasterol, and -8.03 for glycyrrhetinic acid. In addition, the synthetic drugs umifenovir, chloroquine, and hydroxychloroquine were used as controls for S protein, while atazanavir and nelfinavir were used for M<sup>pro</sup>. Key hydrogen bonds and hydrophobic interactions between natural compounds and the respective viral proteins were identified, allowing us to explain the great affinity obtained in those compounds with the lowest binding energies. These results suggest that these natural compounds could potentially be useful as drugs to be experimentally evaluated against COVID-19. </p>

scholarly journals Virtual Screening of Plant-Derived Compounds Against SARS-CoV-2 Viral Proteins Using Computational Tools

2020 ◽  
Author(s):  
Maria Antonela Zigolo ◽  
Matías Rivero Goytia ◽  
Hugo Ramiro Poma ◽  
Verónica Rajal ◽  
Veronica Patricia Irazusta
Keyword(s):  
Hydrophobic Interactions ◽  
Viral Proteins ◽  
Natural Compounds ◽  
Docking Studies ◽  
Binding Energies ◽  
Host Cells ◽  
Computational Tools ◽  
S Protein ◽  
Synthetic Drugs ◽  
Main Protease

<p>The new SARS-CoV-2, responsible for the COVID-19 pandemic, has been threatening public health worldwide for half a year. The aim of this work was to evaluate compounds of natural origin, mainly from medicinal plants, as potential SARS-CoV-2 inhibitors through docking studies. The viral spike (S) glycoprotein and the main protease M<sup>pro</sup>, involved in the recognition of virus by host cells and in viral replication, respectively, were the main molecular targets in this study. </p> <p>The best energy binding values for S protein were, in kcal/mol: -19.22 for glycyrrhizin, -17.84 for gitoxin, -12.05 for dicumarol, -10.75 for diosgenin, and -8.12 for delphinidin. For M<sup>pro</sup> were, in kcal/mol: -9.36 for spirostan, -8.75 for <i>N</i>-(3-acetylglycyrrhetinoyl)-2-amino-propanol, -8.41 for α-amyrin, -8.35 for oleanane, -8.11 for taraxasterol, and -8.03 for glycyrrhetinic acid. In addition, the synthetic drugs umifenovir, chloroquine, and hydroxychloroquine were used as controls for S protein, while atazanavir and nelfinavir were used for M<sup>pro</sup>. Key hydrogen bonds and hydrophobic interactions between natural compounds and the respective viral proteins were identified, allowing us to explain the great affinity obtained in those compounds with the lowest binding energies. These results suggest that these natural compounds could potentially be useful as drugs to be experimentally evaluated against COVID-19. </p>

scholarly journals MOLECULAR DOCKING STUDIES ON SCREENING AND ASSESSMENT OF SELECTED BIOFLAVONOIDS AS POTENTIAL INHIBITORS OF COVID-19 MAIN PROTEASE

2020 ◽  
pp. 174-178
Author(s):  
SHAILENDRA SANJAY SURYAWANSHI ◽  
POOJA BHAVAKANA JAYANNACHE ◽  
RAJKUMAR SANJAY PATIL ◽  
PALLED MS ◽  
ALEGAON SG
Keyword(s):  
Molecular Docking ◽  
Treatment Options ◽  
Docking Studies ◽  
Binding Energies ◽  
Molecular Docking Studies ◽  
Discovery Studio ◽  
Main Protease ◽  
Potential Inhibitors ◽  
Binding Energy Calculations ◽  
Native Ligand

Objectives: The objective of the study was to screen and assess the selected bioactive bioflavonoids in medicinal plants as potential coronaviruses (CoV) main protease (Mpro) inhibitors using molecular docking studies. Methods: We have investigated several bioflavonoids which include apigenin, galangin, glycitein, luteolin, morin, naringin, resveratrol, and rutin. Nelfinavir and lopinavir were used as standard antiviral drugs for comparison. Mpro was docked with selected compounds using PyRx 0.8 and docking was analyzed by PyRx 0.8 and Biovia Discovery Studio 2019. Results: The binding energies obtained from the docking of 6LU7 with native ligand, nelfinavir, lopinavir, apigenin, galangin, glycitein, luteolin, morin, naringin, resveratrol, and rutin were found to be −7.4, −8.3, −8.0, −7.8, −7.3, −7, −7.4, −7.6, −7.8, −6.9, and −9 kcal/mol, respectively. Conclusion: From the binding energy calculations, we can conclude that nelfinavir and lopinavir may represent potential treatment options and apigenin, galangin, glycitein, luteolin, morin, naringin, resveratrol, and rutin found to possess the best inhibitors of CoV disease-19 main protease.

scholarly journals Natural Compounds from Djiboutian Medicinal Plants as Inhibitors of COVID-19 by in Silico Investigations

2020 ◽  
Author(s):  
abdirahman elmi ◽  
S. al jawad sayem ◽  
Mohamed Ahmed ◽  
fatouma mohamed
Keyword(s):  
Medicinal Plants ◽  
Natural Compounds ◽  
Binding Energies ◽  
Receptor Binding Domain ◽  
Global Pandemic ◽  
Main Protease ◽  
Target Sites ◽  
Better Than

The new coronavirus type SARS-Cov 2 (severe acute respiratory syndrome), which appeared in autumn 2019 in China, became a global pandemic in a few months. In this work, we looked for the potential anti SARS-Cov 2 of the compounds isolated from three Djiboutian medicinal plants namely Acacia seyal, Cymbopogon commutatus, and Indigofera caerulea. For this we carried out a docking with nine biomolecules, β-Sitosterol , Quercetin, Catechin, Lupeol, Rutin, Kaempferol, Gallic acid, Piperitone and Limonene on three target sites which are SARS-CoV-2 main protease (Mp), SARS-CoV-2 receptor binding domain (RBD) and human furin protease. These targets are chosen because of their role in the process of penetration of the virus into human cells and its multiplication. The phenolic compounds have a very good afinity on these three target sites with binding energies of up to -9.098 kcal/mol for rutin on SARS-CoV-2 Mp, much better than the two reference drugs hydroxychloroquine (-5.816 kcal / mol) and remdesivir (-7.194 kcal/mol). These natural compounds do not present toxicities and can be used pending In vitro and In vivo evaluations.

scholarly journals Natural Compounds as Inhibitors of SARS-CoV-2 Main Protease (3CLpro): A Molecular Docking and Simulation Approach to Combat COVID-19

2020 ◽  
Author(s):  
Md Tabish Rehman ◽  
Mohamed F AlAjmi ◽  
Afzal Hussain
Keyword(s):  
Clinical Trials ◽  
Hydrophobic Interactions ◽  
Rapid Development ◽  
Economic Loss ◽  
Binding Pocket ◽  
Natural Compounds ◽  
Active Site Residues ◽  
Reference Drug ◽  
Drug Molecules ◽  
Main Protease

<p></p><p>Recently, the emergence and dissemination of SARS-CoV-2 has caused high mortality and enormous economic loss. In the fight against COVID-19, the rapid development of new drug molecules is the need of hour. However, the conventional approaches of drug development is time consuming and expensive in nature. In this study, we have adopted an alternative approach to identify lead molecules from natural sources using high throughput virtual screening approach. Ligands from natural compounds library from Selleck Inc (L1400) have been screened to evaluate their ability to bind and inhibit the main protease (M<sup>pro</sup> or 3CL<sup>pro</sup>) of SARS-CoV-2, which is a potential drug target. We found that Kaempferol, Quercetin, and Rutin were able to bind at the substrate binding pocket of 3CL<sup>pro</sup> with high affinity (10<sup>5</sup>-10<sup>6</sup> M<sup>-1</sup>) and interact with the active site residues such as His41 and Cys145 through hydrogen bonding and hydrophobic interactions. In fact, the binding affinity of Rutin was much higher than Chloroquine (1000 times) and Hydroxychloroquine (100 times) and was comparable to that of the reference drug Remdesivir, which is in clinical trials to treat COVID-19 patients. The results suggest that natural compounds such as flavonoids have the potential to be developed as novel inhibitors of SARS-CoV-2 with a comparable potency as that of Remdesivir. However, their clinical usage on COVID-19 patients is a subject of further investigations and clinical trials.</p><br><p></p>

scholarly journals Molecular docking identification of plant-derived inhibitors of the COVID-19 main protease

2021 ◽  
Vol 103 (3) ◽  
pp. 37-46
Author(s):  
S.S. Bhujbal ◽  
◽  
M. Kale ◽  
B. Chawale ◽  
◽  
...  
Keyword(s):  
Bioactive Compounds ◽  
Drug Target ◽  
Viral Proteins ◽  
Natural Compounds ◽  
Therapeutic Agents ◽  
High Rate ◽  
Therapeutic Drug ◽  
Research Organizations ◽  
Main Protease ◽  
Modeling Techniques

COVID-19 cases increase at a high rate and become dangerous in recent months. As a consequence, some healthcare and research organizations are attempting to find an effective cure for the COVID-19 outbreak. Many natural products have been reported to have powerful activity against COVID-19 in recent research studies. The primary aim of this article is to establish natural bioactive compounds with suitable antiviral properties. Lui et al. have reported in their study that SARS-Cov-2 main protease is present in a crystalline structure known as a novel therapeutic drug target. It is important to inhibit SARS-Cov-2 main protease to stop the replication of viral proteins. In this study natural compounds were screened using molecular modeling techniques to investigate probable bioactive compounds that block SARS-Cov-2. From these studies many natural compounds were found to have the potential to interact with viral proteins and show inhibitory activity against COVID-19 main protease (Mpro) and these natural compounds were also compared to known antiviral drugs such as Saquinavir and Remdesivir. Besides that, additional research is needed before these potential leads can be developed into natural therapeutic agents against COVID-19 to fight the epidemic.

scholarly journals Discovery of Fungal Metabolites Bergenin, Quercitrin and Dihydroartemisinin as Potential Inhibitors Against Main Protease of SARS-CoV-2

2020 ◽  
Author(s):  
Ravi Patel ◽  
Akash Vanzara ◽  
Nimisha Patel ◽  
Ajit Vasava ◽  
Sachin Patil ◽  
...  
Keyword(s):  
Bioactive Compounds ◽  
Active Site ◽  
Electrostatic Interactions ◽  
Hydrophobic Interactions ◽  
Binding Energies ◽  
Crystallographic Structure ◽  
Medicinal Uses ◽  
Main Protease ◽  
Cyathus Stercoreus ◽  
Potential Inhibitors

Emergence of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infection has given rise to COVID-19 pandemic, that is wreaking havoc worldwide. Therefore, there is an urgent need to find out novel drugs to combat SARS-CoV-2 infection. In this backdrop, the present study was aimed to assess potent bioactive compounds from different fungi as potential inhibitors of SARS-CoV-2 main protease (M<sup>pro</sup>) using an <i>in-silico</i> analysis. Nearly 118 bioactive compounds were extracted from <i>Dictyophora indusiata</i>, <i>Geassstrum triplex</i> and <i>Cyathus stercoreus </i>and identified using HR LC/MS analysis. Of which, only bergenin (<i>D. indusiata</i>), quercitrin (<i>G. triplex</i>) and dihydroartemisinin (<i>C. stercoreus</i>) were selected based on their medicinal uses, binding score and active site covered. The 6LU7, a protein crystallographic structure of SARS-CoV-2 M<sup>pro</sup>, was docked with bergenin, quercitrin and dihydroartemisinin using Autodock 4.2 and the binding energies obtained were -7.86, -10.29 and -7.20 kcal/mol, respectively. Bergenin, quercitrin and dihydroartemisinin formed hydrogen bond, electrostatic interactions and hydrophobic interactions with foremost active site amino acids THR190, GLU166, GLN189, GLY143, HIS163, HIS164, CYS145 and PHE140. Present investigation suggests that these three drugs may be used as alternative inhibitors against SARS-CoV-2 M<sup>pro</sup>. However, further research is necessary to assess <i>in vitro</i> potential of these drugs. To the best of our knowledge, present investigation reported these three bioactive compounds of fungal origin for the first time.

scholarly journals Screening, simulation, and optimization design of small molecule inhibitors of the SARS-CoV-2 spike glycoprotein

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245975
Author(s):  
Chuancai Sun ◽  
Jian Zhang ◽  
Jiao Wei ◽  
Xiaoli Zheng ◽  
Xianyang Zhao ◽  
...  
Keyword(s):  
Small Molecule ◽  
Conformational Changes ◽  
Binding Sites ◽  
Optimization Design ◽  
Binding Energies ◽  
Host Cells ◽  
Spike Glycoprotein ◽  
S Protein ◽  
Simulation And Optimization ◽  
Interaction Sites

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak is a public health emergency of international concern. The spike glycoprotein (S protein) of SARS-CoV-2 is a key target of antiviral drugs. Focusing on the existing S protein structure, molecular docking was used in this study to calculate the binding energy and interaction sites between 14 antiviral molecules with different structures and the SARS-CoV-2 S protein, and the potential drug candidates targeting the SARS-CoV-2 S protein were analyzed. Tizoxanide, dolutegravir, bictegravir, and arbidol were found to have high binding energies, and they effectively bind key sites of the S1 and S2 subunits, inhibiting the virus by causing conformational changes in S1 and S2 during the fusion of the S protein with host cells. Based on the interactions among the drug molecules, the S protein and the amino acid environment around the binding sites, rational structure-based optimization was performed using the molecular connection method and bioisosterism strategy to obtain Ti-2, BD-2, and Ar-3, which have much stronger binding ability to the S protein than the original molecules. This study provides valuable clues for identifying S protein inhibitor binding sites and the mechanism of the anti-SARS-CoV-2 effect as well as useful inspiration and help for the discovery and optimization of small molecule S protein inhibitors.

scholarly journals Molecular Docking Studies on the Anti-viral Effects of Compounds From Kabasura Kudineer on SARS-CoV-2 3CLpro

2020 ◽  
Vol 7 ◽  
Author(s):  
Savariar Vincent ◽  
Selvaraj Arokiyaraj ◽  
Muthupandian Saravanan ◽  
Manoj Dhanraj
Keyword(s):  
Molecular Docking ◽  
Critical Role ◽  
Drug Repurposing ◽  
Docking Studies ◽  
World Health ◽  
Synthetic Drugs ◽  
Energy Score ◽  
Main Protease ◽  
Novel Coronavirus ◽  
Health Organization

The COVID-19 has now been declared a global pandemic by the World Health Organization. No approved drug is currently available; therefore, an urgent need has been developed for any antiviral therapy for COVID-19. Main protease 3CLpro of this novel Coronavirus (SARS-CoV-2) play a critical role in the disease propagation, and hence represent a crucial target for the drug discovery. Herein, we have applied a bioinformatics approach for drug repurposing to identify the possible potent inhibitors of SARS-CoV-2 main proteases 3CLpro (6LU7). In search of the anti-COVID-19 compound, we selected 145 phyto-compounds from Kabasura kudineer (KK), a poly-herbal formulation recommended by AYUSH for COVID-19 which are effective against fever, cough, sore throat, shortness of breath (similar to SARS-CoV2-like symptoms). The present study aims to identify molecules from natural products which may inhibit COVID-19 by acting on the main protease (3CLpro). Obtained results by molecular docking showed that Acetoside (−153.06), Luteolin 7 -rutinoside (−134.6) rutin (−133.06), Chebulagic acid (−124.3), Syrigaresinol (−120.03), Acanthoside (−122.21), Violanthin (−114.9), Andrographidine C (−101.8), myricetin (−99.96), Gingerenone -A (−93.9), Tinosporinone (−83.42), Geraniol (−62.87), Nootkatone (−62.4), Asarianin (−79.94), and Gamma sitosterol (−81.94) are main compounds from KK plants which may inhibit COVID-19 giving the better energy score compared to synthetic drugs. Based on the binding energy score, we suggest that these compounds can be tested against Coronavirus and used to develop effective antiviral drugs.

scholarly journals Natural compounds as potential inhibitors of novel coronavirus (COVID-19) main protease: An in silico study

2020 ◽  
Author(s):  
Amaresh Mishra ◽  
Yamini Pathak ◽  
Vishwas Tripathi
Keyword(s):  
In Silico ◽  
Structural Diversity ◽  
Natural Compounds ◽  
Binding Energies ◽  
Maslinic Acid ◽  
Main Protease ◽  
In Silico Studies ◽  
Gallocatechin Gallate ◽  
Novel Coronavirus ◽  
Potential Inhibitors

Abstract COVID-19 pandemic, a novel coronavirus disease is caused by severe acute respiratory syndrome corona virus, SARS-CoV-2. It was first reported in Wuhan, China and has now expanded to more than 190 countries across the world. Till date, there is no specific medication available to prevent or target SARS CoV-2 infection. Very recently, the crystal structure of COVID- 19 main protease (Mpro) was revealed by Liu et al. (2020). SARS-CoV-2 main protease (Mpro) is a key enzyme that plays a crucial role in viral replication and transcription. Thus, Mpro could be a promising target to inhibit SARS-CoV-2 infection. Natural compounds due to their structural diversity and safety are considered as an excellent source of antiviral drugs. In this study, we selected Herbacetin, Rhoifolin, Pectolinarin, Apigenin, Luteolin, Amentoflavone, Daidzein, Puerarin, Epigallocatechin, Gallocatechin gallate, Resveratrol, Maslinic acid, Piperine and Ganomycin B to target the SARS-CoV-2 main protease (Mpro) using in silico tools. These compounds were examined based on ADME, drug likeness, docking studies, MD simulations using CABS-flex 2.0, and prediction of major toxicity parameters (hepatotoxicity & cytotoxicity) to check the safety aspects of the selected compounds. We also investigated the similarity of these compounds, if any, with FDA approved drugs using Swiss similarity. The docking results were found in the order of Amentoflavone (-9.13 kcal/mol), Ritonavir (-8.52 kcal/mol), Lopinavir (-8.5 kcal/mol), Puerarin (-7.97 kcal/mol), Maslinic acid (-7.97 kcal/mol), Piperine (-7.65 kcal/mol), Gallocatechin gallate (-7.59 kcal/mol), Luteolin (-7.58 kcal/mol), Apigenin (-7.42 kcal/mol), Resveratrol (-7.41 kcal/mol), Herbacetin (-7.4 kcal/mol), Daidzein (-7.32 kcal/mol), Rhoifolin (-6.71 kcal/mol), Ganomycin B (-6.46 kcal/mol), Epigallocatechin (-6.13 kcal/mol), and Pectolinarin (-5.88 kcal/mol). Among these selected natural compounds, Amentoflavone and Puerarin were the two top leads which showed the lowest binding energies. Interestingly, Amentoflavone showed highest binding affinity among all the selected compounds. Our promising findings based on in-silico studies warrants further clinical trial in order to use these compounds as potential inhibitors of SARS-CoV-2 protease.

scholarly journals Virtual Screening of Anti-Viral Drugs and Natural Compounds for Potential Inhibition of the Novel SARS-Cov-2 Spike Receptor-Binding Domain

2020 ◽  
Author(s):  
Shilu M. Mathew ◽  
Fatiha Benslimane ◽  
Asmaa A. Althani ◽  
Hadi M. Yassine
Keyword(s):  
Receptor Binding ◽  
Protein Structures ◽  
Natural Compounds ◽  
Binding Domain ◽  
Host Cells ◽  
Receptor Binding Domain ◽  
Binding Modes ◽  
S Protein ◽  
Computational Screening ◽  
Natural Drugs

Background: The spike (S) protein of SARS-CoV-2 harbors the receptor-binding domain (RBD) that mediates the virus's entry to host cells. The aim of this study was to identify novel inhibitors that target the RBD domain of S-protein through computational screening of chemical and natural compounds. Method: The S protein was modelled from the recently resolved and the previously described SARS-CoV protein structures. CLC Drug Discovery was used to computationally screen for potential inhibitory effects of currently prescribed drugs (n= 22) anti-viral natural drugs (n=100), natural compounds (n= 35032). QSAR was also performed. Results: Among currently precribed drugs to treat SARS-CoV2, hydroxychloroquine and favipiravir were identified as the best binders with an average of 4Hbonds, the binding affinity (BA): -36.66 kcal·mol−1, and interaction energy (IE): -6.63 kcal·mol−1. After the evaluation of anti-viral compounds, fosamprenavir and abacavir showed effective binding of 5H-bonds, with average BA: -18.75 kcal·mol−1, and IE: -3.57 kcal·mol−1. Furthermore, screening of 100 natural anti-viral compounds predicted potential binding modes of glycyrrhizin, nepritin, punicalagin, EGCG, and theaflavin (average BA: -49.88 kcal·mol−1, and IE: -4.35 kcal·mol−1). Additionally, the study reports 25 natural compounds that showed effective binding with an improved average BA: 51.46 kcal·mol−1. Conclusion: Using computational screening, we identified potential SARSCoV-2 spike inhibitors that bind to the RBD region.

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