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

10.26434/chemrxiv.12115638.v1 ◽

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. 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.

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

Current Chinese Chemistry ◽

10.2174/2666001601666210322121802 ◽

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.

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

10.26434/chemrxiv.12033774.v1 ◽

2020 ◽

Cited By ~ 2

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.

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Human basigin (CD147) does not directly interact with SARS-CoV-2 spike glycoprotein

10.1101/2021.02.22.432402 ◽

2021 ◽

Author(s):

Robert J. Ragotte ◽

David Pulido ◽

Francesca R. Donnellan ◽

Giacomo Gorini ◽

Hannah Davies ◽

...

Keyword(s):

Receptor Binding ◽

Therapeutic Target ◽

Mammalian Cells ◽

Direct Interaction ◽

Binding Domain ◽

Host Cells ◽

Size Exclusion ◽

Receptor Binding Domain ◽

Spike Glycoprotein ◽

Mortality And Morbidity

AbstractBasigin, or CD147, has been reported as a co-receptor used by SARS-CoV-2 to invade host cells. Basigin also has a well-established role in Plasmodium falciparum malaria infection of human erythrocytes where it is bound by one of the parasite’s invasion ligands, reticulocyte binding protein homolog 5 (RH5). Here, we sought to validate the claim that the receptor binding domain (RBD) of SARS-CoV-2 spike glycoprotein can form a complex with basigin, using RH5-basigin as a positive control. Using recombinantly expressed proteins, size exclusion chromatography and surface plasmon resonance, we show that neither RBD nor full-length spike glycoprotein bind to recombinant human basigin (either expressed in E. coli or mammalian cells). Given the immense interest in SARS-CoV-2 therapeutic targets, we would caution the inclusion of basigin in this list on the basis of its reported direct interaction with SARS-CoV-2 spike glycoprotein.ImportanceReducing the mortality and morbidity associated with COVID-19 remains a global health priority. Critical to these efforts is the identification of host factors that are essential to viral entry and replication. Basigin, or CD147, was previously identified as a possible therapeutic target based on the observation that it may act as a co-receptor for SARS-COV-2, binding to the receptor binding domain of the spike protein. Here, we show that there is no direct interaction between the RBD and basigin, casting doubt on its role as a co-receptor and plausibility as a therapeutic target.

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Inhibition Ability of Natural Compounds on Receptor-Binding Domain of SARS-CoV2: An In Silico Approach

Pharmaceuticals ◽

10.3390/ph14121328 ◽

2021 ◽

Vol 14 (12) ◽

pp. 1328

Author(s):

Miroslava Nedyalkova ◽

Mahdi Vasighi ◽

Subrahmanyam Sappati ◽

Anmol Kumar ◽

Sergio Madurga ◽

...

Keyword(s):

Machine Learning ◽

Molecular Docking ◽

Binding Affinity ◽

Receptor Binding ◽

In Silico ◽

Experimental Studies ◽

Natural Compounds ◽

Binding Domain ◽

Machine Learning Techniques ◽

Receptor Binding Domain

The lack of medication to treat COVID-19 is still an obstacle that needs to be addressed by all possible scientific approaches. It is essential to design newer drugs with varied approaches. A receptor-binding domain (RBD) is a key part of SARS-CoV-2 virus, located on its surface, that allows it to dock to ACE2 receptors present on human cells, which is followed by admission of virus into cells, and thus infection is triggered. Specific receptor-binding domains on the spike protein play a pivotal role in binding to the receptor. In this regard, the in silico method plays an important role, as it is more rapid and cost effective than the trial and error methods using experimental studies. A combination of virtual screening, molecular docking, molecular simulations and machine learning techniques are applied on a library of natural compounds to identify ligands that show significant binding affinity at the hydrophobic pocket of the RBD. A list of ligands with high binding affinity was obtained using molecular docking and molecular dynamics (MD) simulations for protein–ligand complexes. Machine learning (ML) classification schemes have been applied to obtain features of ligands and important descriptors, which help in identification of better binding ligands. A plethora of descriptors were used for training the self-organizing map algorithm. The model brings out descriptors important for protein–ligand interactions.

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

10.26434/chemrxiv.12033774 ◽

2020 ◽

Cited By ~ 1

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.

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Amoxicillin Trihydrate-Clavulanate Potassium As Potential Inhibitor of 2019 Novel Coronavirus Main Protease with Strong Receptor-Binding Domain (RBD), Molecular Docking and SAR Study

SSRN Electronic Journal ◽

10.2139/ssrn.3580230 ◽

2020 ◽

Author(s):

Khedidja benarous ◽

Talia Serseg ◽

Mohamed Yousfi

Keyword(s):

Molecular Docking ◽

Receptor Binding ◽

Binding Domain ◽

Receptor Binding Domain ◽

Potential Inhibitor ◽

Main Protease ◽

Amoxicillin Trihydrate ◽

Novel Coronavirus ◽

Sar Study

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Amoxicillin and Clavulanate as Potential Multiple Effect Inhibitors of 2019 Novel Coronavirus Main Protease and RNA-Dependent RNA Polymerase with Strong Receptor-Binding Domain (RBD), Molecular Docking and SAR Study

SSRN Electronic Journal ◽

10.2139/ssrn.3618303 ◽

2020 ◽

Author(s):

Khedidja benarous ◽

Talia Serseg ◽

Mohamed Yousfi

Keyword(s):

Molecular Docking ◽

Rna Polymerase ◽

Receptor Binding ◽

Binding Domain ◽

Receptor Binding Domain ◽

Rna Dependent Rna Polymerase ◽

Multiple Effect ◽

Main Protease ◽

Novel Coronavirus ◽

Sar Study

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

Infectious Disorders - Drug Targets ◽

10.2174/1871526520666200804161650 ◽

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).

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An in Silico Scientific Basis for LL-37 as a Therapeutic and Vitamin D as Preventive for Covid-19.

10.26434/chemrxiv.12928202.v1 ◽

2020 ◽

Author(s):

Kiran Bharat Lokhande ◽

Tanushree Banerjee ◽

K. Venkateswara Swamy ◽

Manisha Deshpande

Keyword(s):

Vitamin D ◽

Receptor Binding ◽

In Silico ◽

Large Body ◽

Inverse Correlation ◽

Medical Practitioner ◽

Binding Domain ◽

The Body ◽

Receptor Binding Domain ◽

Vitamin D Levels

Even as clinical trials are underway for vaccines and therapeutics for Covid-19, establishment of modalities with a strong and complete foundation is still awaited and until then, the uncertainty remains associated. Thus, there is a requirement to research as many new and different types of approaches as possible to tackle the pandemic. In this report, in silico scientific findings are presented, which are indicative of the putative potential for the use of the LL-37 human anti-microbial peptide as a therapeutic or possibly even as a prophylactic against SARS-CoV-2. This indication is mainly based on the high structural similarity of LL-37 to the N-terminal helix of the receptor-binding domain of SARS-CoV-2, and the positive prediction of binding of LL-37 to the receptor-binding domain of SARS-CoV-2. Also, as Vitamin D is known to upregulate the expression of LL-37, the vitamin is a candidate preventive molecule. This report also provides the possible basis for why there is an inverse correlation between Vitamin D levels in the body and the severity of or susceptibility to Covid-19, as described in a large body of published literature. The path for development of LL-37 as a therapeutic could be of lesser duration, as LL-37 is native to the human body. With the scientific link put forth in this work, Vitamin D could be used at an effective, medically prescribed dose as a preventive measure. As Vitamin D is insoluble in water, it should be taken only in consultation with a medical practitioner to prevent adverse effects of its accumulation in the body. The information in this report would be valuable in bolstering the worldwide efforts to control the pandemic as early as possible.

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