scholarly journals Molecular Docking study of Receptor Binding Domain of SARS-CoV-2 Spike Glycoprotein with Saikosaponin, a Triterpenoid Natural Product

2020 ◽  
Author(s):  
Tamal Goswami ◽  
Bhaskar Bagchi
Keyword(s):  
Molecular Docking ◽  
Receptor Binding ◽  
Docking Study ◽  
Binding Domain ◽  
Target Cells ◽  
Receptor Binding Domain ◽  
Spike Glycoprotein ◽  
Molecular Docking Study ◽  
Computational Docking ◽  
Angiotensin Converting Enzyme 2

The appearance of SARS-CoV-2 has resulted ~19000 deaths and ~423000 infections worldwide as of March 24, 2020. Coronavirus spike (S) glycoproteins hooks on target cells and binds to the angiotensin-converting enzyme 2 (ACE2) receptor. Recent researches speculated that residues 331 to 524 of the S glycoprotein of the receptor binding domain (RDB) of the spike is the most crucial target and this side was very important for computational docking. In the present study we have considered a series of saikosaponins and molecular docking was performed. Most of the docked molecules bind favorably to the RDB region of the spike glycoprotein and among them Saikosaponin B4 is the best inhibitor.

scholarly journals Molecular Docking study of Receptor Binding Domain of SARS-CoV-2 Spike Glycoprotein with Saikosaponin, a Triterpenoid Natural Product

2020 ◽  
Author(s):  
Tamal Goswami ◽  
Bhaskar Bagchi
Keyword(s):  
Molecular Docking ◽  
Receptor Binding ◽  
Docking Study ◽  
Binding Domain ◽  
Target Cells ◽  
Receptor Binding Domain ◽  
Spike Glycoprotein ◽  
Molecular Docking Study ◽  
Computational Docking ◽  
Angiotensin Converting Enzyme 2

The appearance of SARS-CoV-2 has resulted ~19000 deaths and ~423000 infections worldwide as of March 24, 2020. Coronavirus spike (S) glycoproteins hooks on target cells and binds to the angiotensin-converting enzyme 2 (ACE2) receptor. Recent researches speculated that residues 331 to 524 of the S glycoprotein of the receptor binding domain (RDB) of the spike is the most crucial target and this side was very important for computational docking. In the present study we have considered a series of saikosaponins and molecular docking was performed. Most of the docked molecules bind favorably to the RDB region of the spike glycoprotein and among them Saikosaponin B4 is the best inhibitor.

Role of key point Mutations in Receptor Binding Domain of SARS-CoV-2 Spike Glycoprotein

2020 ◽  
Vol 20 ◽  
Author(s):  
Bipin Singh
Keyword(s):  
Receptor Binding ◽  
Point Mutations ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
Spike Glycoprotein ◽  
Angiotensin Converting Enzyme 2 ◽  
Recent Outbreak ◽  
Novel Coronavirus ◽  
Genomic Similarity

: The recent outbreak of novel coronavirus (SARS-CoV-2 or 2019-nCoV) and its worldwide spread is posing one of the major threats to human health and the world economy. It has been suggested that SARS-CoV-2 is similar to SARSCoV based on the comparison of the genome sequence. Despite the genomic similarity between SARS-CoV-2 and SARSCoV, the spike glycoprotein and receptor binding domain in SARS-CoV-2 shows the considerable difference compared to SARS-CoV, due to the presence of several point mutations. The analysis of receptor binding domain (RBD) from recently published 3D structures of spike glycoprotein of SARS-CoV-2 (Yan, R., et al. (2020); Wrapp, D., et al. (2020); Walls, A. C., et al. (2020)) highlights the contribution of a few key point mutations in RBD of spike glycoprotein and molecular basis of its efficient binding with human angiotensin-converting enzyme 2 (ACE2).

Discovery of potential inhibitors of the receptor-binding domain (RBD) of pandemic disease-causing SARS-CoV-2 Spike Glycoprotein from Triphala through molecular docking

2021 ◽  
Vol 01 ◽  
Author(s):  
Sharuk L. Khan ◽  
Falak A. Siddiqui ◽  
Mohd Sayeed Shaikh ◽  
Nitin V. Nema ◽  
Aijaz A. Shaikh
Keyword(s):  
Molecular Docking ◽  
Hydrogen Bonds ◽  
Receptor Binding ◽  
Chemical Constituents ◽  
Antioxidant Properties ◽  
Binding Domain ◽  
Quality Data ◽  
Receptor Binding Domain ◽  
Spike Glycoprotein

Background: COVID-19 (SARS-CoV-2 infection) has affected almost every region of the world. Presently, there is no defined line of treatment available for it. Triphala is already proven to have a safe biological window and well known for its antioxidant and immunomodulatory properties. Objective: Present work has been carried out to study Triphala's effectiveness for the treatment of COVID-19. Methods: The Receptor-binding domain (RBD) of SARS-CoV-2 Spike Glycoprotein responsible for the invasion into the host cell, which leads to further infection. The molecular docking (MD) was performed to explore the binding affinities (kcal/mol) of Triphala's chemical constituents and compared them with the existing drugs under investigation for the treatment of COVID-19 epidemiology. Results: Chebulinic acid binding affinity -8.5 kcal/mol with the formation of 10 hydrogen bonds. Almost all the major chemical constituents have formed two or more hydrogen bonds with RBD of SARS-CoV-2 Spike Glycoprotein. Conclusion: The present study showed that Triphala might perform vital roles in the treatment of COVID-19 and expand its usefulness to physicians to treat this illness. There is a need to complete the in-vitro, in-vivo biological testing of Triphala on SARS-CoV-2 disease to create more quality data. The binding mode of Chebulinic acid in the allosteric cavity allows a better understanding of RBD of SARS-CoV-2 Spike Glycoprotein target and provides insight for the design of new inhibitors. Triphala is already proven to have a safe biological window, which indicates we can skip the pre-clinical trials. Apart from this, Triphala is well known for its antioxidant properties, which ultimately improves the immunity of the COVID-19 patient.

scholarly journals Computational Approach Revealed Potential Affinity of Antiasthmatics Against Receptor Binding Domain of 2019n-Cov Spike Glycoprotein

2020 ◽  
Author(s):  
LAMIAE ELKHATTABI ◽  
Hicham Charoute ◽  
Rachid Saile ◽  
Abdelhamid Barakat
Keyword(s):  
Molecular Docking ◽  
Receptor Binding ◽  
In Silico ◽  
Cyclic Peptide ◽  
Direct Interaction ◽  
Binding Domain ◽  
Binding Energies ◽  
Receptor Binding Domain ◽  
Spike Glycoprotein ◽  
Pubchem Database

The novel COVID-19 pandemic is now a health threat, with a deep-felt impact worldwide. The new coronavirus 2019 (2019 n-Cov) binds to host human receptors through Receptor Binding Domain RBD of Spike glycoprotein (S), making it a prominent drug target. The present study aims to identify new potential hits that can inhibit the S protein using in silico approaches. Several natural and synthetics compounds (antiasthmatics, Antiviral, Antimalarial, Antibacterial, Anti-Inflammatory, cyclic peptide, and cyclic bis) were screened by molecular docking using AutoDock Vina. Additionally, we tested calcitriol and three known drugs (Azithromycin, HydroxyChloroquine, and Chloroquine ) against the spike protein to found if they have any direct interaction.<br>Our finding consists of 4 potential synthetic compounds from PubChem database, known for their antiasthmatic effects, that show highly binding energies each (-8.6 kcal/mol, 7.7kcal/mol, -7.2 kcal/mol and -7.0 kcal/mol). Another 5 natural compounds from the South African natural sources database (SANCDB) that bind to RBD of Spike with significant energy each: (Marchantin C with -7.3 kcal/mol, Riccardin C with -7.0 kcal/mol, Digitoxigenin-glucoside with -6.9 kcal/mol, D-Friedoolean-14-en-oic acid with -6.8 kcal/mol and, Spongotine A with -6.7 kcal/mol). The FaF-Drugs server was used to evaluate the drug-like properties of the identified compounds. Additionally, Calcitriol, Azithromycin, and HydroxyChloroquine have an appreciable binding affinity to 2019-nCoV S, suggesting a possible mechanism of action. Using in silico approaches like molecular docking and pharmacokinetic properties, we showed new potential inhibitors. Our findings need further analysis, and chemical design for more effective derivatives of these compounds speculated to disrupt the viral recognition of host receptors.

Design, synthesis and in silico studies of novel N-(2-aminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide derivatives targeting receptor-binding domain (RBD) of SARS-CoV-2 Spike Glycoprotein and evaluation as antimicrobial and antimalarial agents

2021 ◽  
Vol 18 ◽  
Author(s):  
Falak A. Siddiqui ◽  
Sharuk L. Khan ◽  
Rajendra P Marathe ◽  
Nitin V. Nemac
Keyword(s):  
Hydrogen Bonds ◽  
Receptor Binding ◽  
Drug Repurposing ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
Spike Glycoprotein ◽  
Design Synthesis ◽  
Angiotensin Converting Enzyme 2 ◽  
In Silico Studies ◽  
Novel Coronavirus

Background: Pneumonia induced by a novel coronavirus (SARS-CoV-2) was named as coronavirus disease 2019 (COVID-19). The Receptor-binding domain (RBD) of SARS-CoV-2 Spike Glycoprotein, causes invasion of the virus into the host cell by attaching with human angiotensin-converting enzyme-2 (hACE-2) which leads to further infection. Objectives: The novel N-(2-aminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide derivatives were designed and synthesized to inhibit the RBD of SARS-CoV-2 Spike Glycoprotein by applying molecular docking tools. Methods: The synthesized products was characterized by Infrared Spectroscopy (IR), and 1H Nuclear Magnetic Resonance (NMR). Results: All the derivatives were found to have a very good binding affinity between -9 to -10.1 kcal/mol, better than the drugs which are under investigation for the treatment of SARS-CoV-2 infection. Compound F1 has formed 4 hydrogen bonds whereas, F4 and F10 formed two hydrogen bonds each with RBD of SARS-CoV-2 Spike Glycoprotein. All the derivatives were subjected to antimicrobial, antifungal, and antimalarial susceptibility. Conclusion: From the above-obtained results, we have concluded that novel N-(2-aminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide derivatives have excellent potential to inhibit the receptor-binding domain (RBD) of SARS-CoV-2 Spike Glycoprotein, which is now an attentive target in designing SARS-CoV-2 inhibitors. This scaffold can hold an effective interest in the development of inhibitors for SARS-CoV-2 in the future if drug repurposing fails to serve the purpose.

scholarly journals Identification of a SARS-like bat coronavirus that shares structural features with the spike glycoprotein receptor-binding domain of SARS-CoV-2

2020 ◽  
Vol 2 (11) ◽  
Author(s):  
Conchita Fraguas Bringas ◽  
David Booth
Keyword(s):  
Receptor Binding ◽  
Structural Features ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
Spike Glycoprotein ◽  
Angiotensin Converting Enzyme 2 ◽  
Reliable Model ◽  
High Conservation ◽  
Host Range Determination ◽  
Bat Coronavirus

SARS-CoV-2 is a recently emerged coronavirus that binds angiotensin-converting enzyme 2 (ACE2) for cell entry via its receptor-binding domain (RBD) on a surface-expressed spike glycoprotein. Studies show that despite its similarities to severe acute respiratory syndrome (SARS) coronavirus, there are critical differences in key RBD residues when compared to SARS-CoV-2. Here we present a short in silico study, showing that SARS-like bat coronavirus Rs3367 shares a high conservation with SARS-CoV-2 in important RBD residues for ACE2 binding: SARS-CoV-2’s Phe486, Thr500, Asn501 and Tyr505; implicated in receptor-binding strength and host-range determination. These features were not shared with other studied bat coronaviruses belonging to the betacoronavirus genus, including RaTG13, the closest reported bat coronavirus to SARS-CoV-2’s spike protein. Sequence and phylogeny analyses were followed by the computation of a reliable model of the RBD of SARS-like bat coronavirus Rs3367, which allowed structural insight of the conserved residues. Superimposition of this model on the SARS-CoV-2 ACE2-RBD complex revealed critical ACE2 contacts are also maintained. In addition, residue Asn488Rs3367 interacted with a previously defined pocket on ACE2 composed of Tyr41, Lys353 and Asp355. When compared to available SARS-CoV-2 crystal structure data, Asn501SARS-CoV-2 showed a different interaction with the ACE2 pocket. Taken together, this study offers molecular insights on RBD-receptor interactions with implications for vaccine design.

scholarly journals In Silico Identification of Potential Therapeutic Agents for COVID-19 Based on Molecular Docking Study of Main Protease and Receptor Binding Domain of Spike Protein.

2021 ◽  
Author(s):  
Vajiheh Eskandari
Keyword(s):  
Folic Acid ◽  
Receptor Binding ◽  
In Silico ◽  
Docking Study ◽  
Binding Domain ◽  
Dynamics Simulation ◽  
Receptor Binding Domain ◽  
Active Site Residues ◽  
Molecular Docking Study ◽  
S Protein

Abstract Severe acute respiratory syndrome coronavirus (SARS-CoV-2) enter the cell by interacting with human angiotensin-converting enzyme 2 (ACE2) receptor through the receptor-binding domain (RBD) of S-protein. In the cell the viral 3-chymotrypsin-like cysteine protease (3CLp) enzyme is essential for its life cycle and controls coronavirus replication. Therefore the S-RBD and 3CLp are hot targets for drugs discovery against SARS-CoV-2. This study was to identify repurposing drugs using in-silico screening, docking and molecular dynamics simulation. The study identified Dibenzoyl Thiamine, Folic Acid and Vitamin B12 against the RBD of S-protein and Dibenzoyl Thiamine, Folic Acid, Fursultiamine and Riboflavin to 3CLp. The strong and stable binding of these safe and cheap vitamins at the important residues (R403, K417, Y449, Y453, N501 and Y505) in S-protein –ACE2 interface and 3CLp active site residues (His 41 and Cys 145), indicating that they could be valuable repurpose drugs for inhibiting SARS-CoV-2 entry into the host and replication.

scholarly journals Comparison of Clinically Approved Molecules on SARS-CoV-2 Drug Target Proteins: A Molecular Docking Study

2020 ◽  
Author(s):  
Hasan Cubuk ◽  
Mehmet Ozbil
Keyword(s):  
Molecular Docking ◽  
Drug Design ◽  
Receptor Binding ◽  
Binding Domain ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Molecular Docking Study ◽  
Target Proteins ◽  
Docking Simulations ◽  
Main Protease

<p>The new type of coronavirus, SARS-CoV-2 has affected more than 6.3 million people worldwide. Since the first day the virus has been spotted in Wuhan, China, there are numerous drug design studies conducted all over the globe. Most of these studies target the receptor-binding domain of spike protein of SASR-CoV-2, which is known to bind human ACE2 receptor and SARS-CoV-2 main protease, vital for the virus’ replication. However, there might be a third target, human furin protease, which cleaves the virus’ S1-S2 domains taking active role in its entry into the host cell. In this study we docked five clinically used drug molecules, favipiravir, hydroxychloroquine, remdesivir, lopinavir, and ritonavir onto three target proteins, receptor binding domain of SARS-CoV-2 spike protein, SARS-CoV-2 main protease, and human furin protease. Results of molecular docking simulations revealed that human furin protease might be targeted against COVID-19. Remdesivir, a nucleic acid derivative, strongly bound to the active site of this protease, suggesting this molecule can be used as a template for designing novel furin protease inhibitorsto fight with the disease. Protein-drug interactions revealed at the molecular level in this study can pave the way for better drug design for each specific target.<br></p>

scholarly journals Understanding the Role of Key Point Mutations in Receptor Binding Domain of SARS-CoV-2 Spike Glycoprotein

2020 ◽  
Author(s):  
Bipin Singh
Keyword(s):  
Receptor Binding ◽  
3D Structure ◽  
Point Mutations ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
Spike Glycoprotein ◽  
Angiotensin Converting Enzyme 2 ◽  
Novel Coronavirus ◽  
Genomic Similarity

The recent outbreak of novel coronavirus (2019-nCoV or SARS-CoV-2) and its spread to the whole world is currently posing one of the major threat to human health and the world economy. It has been suggested that 2019-nCoV is similar to SARS-CoV based on the genome sequence comparison. Despite the genomic similarity between SARS-CoV and SARS-CoV-2, the spike glycoprotein and receptor binding domain in SARS-CoV-2 shows considerable difference compared to SARS-CoV, due to the presence of several point mutations. We analyzed the receptor binding domain (RBD) from recently published 3D structure of spike glycoprotein of SARS-CoV-2 and compared with RBD of SARS-CoV. The observations highlight few important features of RBD in the light of the recently published findings from the 3D structures of spike glycoprotein and its complex with human angiotensin-converting enzyme 2 (ACE2) (Yan, R., et al. (2020); Wrapp, D., et al. (2020); Walls, A. C., et al. (2020)).

scholarly journals SARS-CoV-2 Structural Analysis of Receptor Binding Domain New Variants from United Kingdom and South Africa

2021 ◽  
Vol 7 ◽  
Author(s):  
Victor Padilla-Sanchez
Keyword(s):  
South Africa ◽  
United Kingdom ◽  
Structural Analysis ◽  
Receptor Binding ◽  
Binding Domain ◽  
The Other ◽  
Receptor Binding Domain ◽  
Converting Enzyme ◽  
Spike Glycoprotein ◽  
Angiotensin Converting Enzyme 2

SARS-CoV-2 has caused more than 80 million infections and close to 2 million deaths worldwide as of January 2021. This pandemic has caused an incredible damage to humanity being it medically and/or financially halting life as we know it. If it were not enough, the current virus is changing to a more deadly form because of the mutations that are arising on its genome. Importantly, two variants have emerged in recent months, one in United Kingdom and the other in South Africa that are more infectious and escape antibody binding. These two variants have mutations in the receptor binding domain of the spike glycoprotein namely N501Y (UK, SA), K417N (SA) and E484K (SA). Here, I present a structural analysis of spike glycoprotein bound to ACE2 (angiotensin converting enzyme 2) where the mutations have been introduced in silico showing the reason why these variants bind better to ACE2 receptors.

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