scholarly journals Arthropod Ectoparasites Have Potential to Bind SARS-CoV-2 via ACE

Viruses ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 708
Author(s):  
Su Datt Lam ◽  
Paul Ashford ◽  
Sandra Díaz-Sánchez ◽  
Margarita Villar ◽  
Christian Gortázar ◽  
...  
Keyword(s):  
Binding Energy ◽  
In Silico ◽  
Protein Sequences ◽  
3D Models ◽  
Spike Protein ◽  
Complex Stability ◽  
Water Flea ◽  
Cat Flea ◽  
Binding Energy Calculations

Coronavirus-like organisms have been previously identified in Arthropod ectoparasites (such as ticks and unfed cat flea). Yet, the question regarding the possible role of these arthropods as SARS-CoV-2 passive/biological transmission vectors is still poorly explored. In this study, we performed in silico structural and binding energy calculations to assess the risks associated with possible ectoparasite transmission. We found sufficient similarity between ectoparasite ACE and human ACE2 protein sequences to build good quality 3D-models of the SARS-CoV-2 Spike:ACE complex to assess the impacts of ectoparasite mutations on complex stability. For several species (e.g., water flea, deer tick, body louse), our analyses showed no significant destabilisation of the SARS-CoV-2 Spike:ACE complex, suggesting these species would bind the viral Spike protein. Our structural analyses also provide structural rationale for interactions between the viral Spike and the ectoparasite ACE proteins. Although we do not have experimental evidence of infection in these ectoparasites, the predicted stability of the complex suggests this is possible, raising concerns of a possible role in passive transmission of the virus to their human hosts.

scholarly journals In-silico Studies of Antimalarial-agent Artemisinin and Derivatives Portray More Potent Binding to Lys353 and Lys31-Binding Hotspots of SARS-CoV-2 Spike Protein than Hydroxychloroquine: Potential Repurposing of Artenimol for COVID-19.

2020 ◽  
Author(s):  
Moussa SEHAILIA ◽  
Smain chemat
Keyword(s):  
Clinical Trials ◽  
In Silico ◽  
Spike Protein ◽  
Antimalarial Agent ◽  
In Silico Studies ◽  
Better Than

<p>The role of hydroxychloroquine to prevent hACE2 from interacting with SARS-CoV-2 Spike protein is unveiled. Artemisinin & derived compounds entangle better than hydroxychloroquine into Lys353 and Lys31 binding hotspots of the virus Spike protein, therefore preventing infection occurs. Since these molecules are effective antivirals with excellent safety track records, their potential repurposing is recommended for clinical trials of COVID-19 patients.</p>

scholarly journals Elucidation of the interactions between SARS-CoV-2 Spike protein and wild and mutant types of IFITM proteins by in silico methods

2021 ◽  
Author(s):  
Nazli Irmak Giritlioglu ◽  
Gizem Koprululu Kucuk
Keyword(s):  
Molecular Docking ◽  
Amino Acid ◽  
Binding Energy ◽  
Hydrogen Bonds ◽  
In Silico ◽  
Protein Complexes ◽  
Protein Product ◽  
Binding Energies ◽  
Spike Protein ◽  
Web Based

COVID-19 is a viral disease that has been a threat to the whole world since 2019. Although effective vaccines against the disease have been developed, there are still points to be clarified about the mechanism of SARS-CoV-2, which is the causative agent of COVID-19. In this study, we determined the binding energies and the bond types of complexes formed by open (6VYB) and closed (6VXX) forms of the Spike protein of SARS-CoV-2 and wild and mutant forms of IFITM1, IFITM2, and IFITM3 proteins using the molecular docking approach. First, all missense SNPs were found in the NCBI Single Nucleotide Polymorphism database (dbSNP) for IFITM1, IFITM2, and IFITM3 and analyzed with SIFT, PROVEAN, PolyPhen-2, SNAP2, Mutation Assessor, and PANTHER cSNP web-based tools to determine their pathogenicity. When at least four of these analysis tools showed that the SNP had a pathogenic effect on the protein product, this SNP was saved for further analysis. Delta delta G (DDG) and protein stability analysis for amino acid changes were performed in the web-based tools I-Mutant, MUpro, and SAAFEC-SEQ. The structural effect of amino acid change on the protein product was made using the HOPE web-based tool. HawkDock server was used for molecular docking and Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) analysis and binding energies of all complexes were calculated. BIOVIA Discovery Studio program was utilized to visualize the complexes. Hydrogen bonds, salt bridges, and non-bonded contacts between Spike and IFITM protein chains in the complexes were detected with the PDBsum web-based tool. The best binding energy among the 6VYB-IFITM wild protein complexes belong to 6VYB-IFITM1 (-46.16 kcal/mol). Likewise, among the 6VXX-IFITM wild protein complexes, the most negative binding energy belongs to 6VXX-IFITM1 (-52.42 kcal/mol). An interesting result found in the study is the presence of hydrogen bonds between the cytoplasmic domain of the IFITM1 wild protein and the S2 domain of 6VYB. Among the Spike-IFITM mutant protein complexes, the best binding energy belongs to the 6VXX-IFITM2 N63S complex (-50.77 kcal/mol) and the worst binding energy belongs to the 6VXX-IFITM3 S50T complex (4.86 kcal/mol). The study suggests that IFITM1 protein may act as a receptor for SARS-CoV-2 Spike protein. Assays must be advanced from in silico to in vitro for the determination of the receptor-ligand interactions between IFITM proteins and SARS-CoV-2.

scholarly journals Understanding the role of galectin inhibitors as potential candidates for SARS-CoV-2 spike protein: in silico studies

RSC Advances ◽  
2020 ◽  
Vol 10 (50) ◽  
pp. 29873-29884 ◽  
Author(s):  
Aaftaab Sethi ◽  
Swetha Sanam ◽  
Sharon Munagalasetty ◽  
Sivaraman Jayanthi ◽  
Mallika Alvala
Keyword(s):  
In Silico ◽  
Spike Protein ◽  
In Silico Studies ◽  
Galectin 3

Galectin 3 have the potential to inhibit the SARS-CoV-2 spike protein. We validated the studies by docking, MD and MM/GBSA calculations.

scholarly journals In-silico Studies of Antimalarial-agent Artemisinin and Derivatives Portray More Potent Binding to Lys353 and Lys31-Binding Hotspots of SARS-CoV-2 Spike Protein than Hydroxychloroquine: Potential Repurposing of Artenimol for COVID-19.

2020 ◽  
Author(s):  
Moussa SEHAILIA ◽  
Smain chemat
Keyword(s):  
Clinical Trials ◽  
In Silico ◽  
Spike Protein ◽  
Antimalarial Agent ◽  
In Silico Studies ◽  
Better Than

<p>The role of hydroxychloroquine to prevent hACE2 from interacting with SARS-CoV-2 Spike protein is unveiled. Artemisinin & derived compounds entangle better than hydroxychloroquine into Lys353 and Lys31 binding hotspots of the virus Spike protein, therefore preventing infection occurs. Since these molecules are effective antivirals with excellent safety track records, their potential repurposing is recommended for clinical trials of COVID-19 patients.</p>

scholarly journals A Possible Role of Pulegone against Glypican-1 for the Treatment of Alzheimer’s Disease through In-Silico Approach

2021 ◽  
Vol 9 (VI) ◽  
pp. 4000-4007
Author(s):  
Nikita Kaushik
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Docking ◽  
Binding Energy ◽  
In Silico ◽  
Target Protein ◽  
Receptor Protein ◽  
Lipinski’S Rule ◽  
Lipinski’S Rule Of Five

Alzheimer’s disease (AD) dementia is a type of neurodegenerative disease, refers to a distinct arrival and certainly functional and mental decline which is linked with age which eventually leads to death. This current study was to demonstrate the role of pulegone against Glypican-1 for the treatment of Alzheimer’s disease through an in-silico approach. Methods: All the information and studies were gleaned from molecular docking. With the use of docking software, Docking was implemented between the target protein GPC1 (PDB ID: 4YWT) and the entire ligands. We preferred GPC1 (PDB ID: 4YWT) as a target protein and several natural compounds such as Rosmarinic acid, Allo ocimene, and Pulegone as ligands. When the preparation of protein is done, in PyRx software we introduced the entire ligand for the process of virtual screening. As reported by the result of PyRx and Lipinski’s Rule of Five, the finest compound against GPC1 with its smallest amount of binding energy was Pulegone. Results: For the procedure of molecular docking between the receptor protein GPC1 (PDB ID: 4YWT) and Pulegone a software called AutoDock Vina was used. The outcome showed 9 poses with distinct binding energy, RMSD LB (Root means square deviation Lower Bound), RMSD UB (Root mean square deviation Upper Bound). Through PyMol (an open-access tool for the visualization of the molecule), the interaction amidst Pulegone and GPC1 can be visualized. Conclusion: The merely compound which can restrain the activity of GPC1 (PDB ID: 4YWT) was Pulegone, based on the in-silico approach. Therefore in the advanced studies, Pulegone can be a capable medicine acquired from natural sources for dealing with Alzheimer’s disease.

scholarly journals Phytochemical Moieties From Indian Traditional Medicine for Targeting Dual Hotspots on SARS-CoV-2 Spike Protein: An Integrative in-silico Approach

2021 ◽  
Vol 8 ◽  
Author(s):  
V. Umashankar ◽  
Sanjay H. Deshpande ◽  
Harsha V. Hegde ◽  
Ishwar Singh ◽  
Debprasad Chattopadhyay
Keyword(s):  
Free Energy ◽  
Binding Energy ◽  
Traditional Medicine ◽  
Binding Affinity ◽  
In Silico ◽  
Binding Free Energy ◽  
Contemporary Literature ◽  
Dynamics Simulation ◽  
Spike Protein ◽  
Syzygium Aromaticum

SARS-CoV-2 infection across the world has led to immense turbulence in the treatment modality, thus demanding a swift drug discovery process. Spike protein of SARS-CoV-2 binds to ACE2 receptor of human to initiate host invasion. Plethora of studies demonstrate the inhibition of Spike-ACE2 interactions to impair infection. The ancient Indian traditional medicine has been of great interest of Virologists worldwide to decipher potential antivirals. Hence, in this study, phytochemicals (1,952 compounds) from eight potential medicinal plants used in Indian traditional medicine were meticulously collated, based on their usage in respiratory disorders, along with immunomodulatory and anti-viral potential from contemporary literature. Further, these compounds were virtually screened against Receptor Binding Domain (RBD) of Spike protein. The potential compounds from each plant were prioritized based on the binding affinity, key hotspot interactions at ACE2 binding region and glycosylation sites. Finally, the potential hits in complex with spike protein were subjected to Molecular Dynamics simulation (450 ns), to infer the stability of complex formation. Among the compounds screened, Tellimagrandin-II (binding energy of −8.2 kcal/mol and binding free energy of −32.08 kcal/mol) from Syzygium aromaticum L. and O-Demethyl-demethoxy-curcumin (binding energy of −8.0 kcal/mol and binding free energy of −12.48 kcal/mol) from Curcuma longa L. were found to be highly potential due to their higher binding affinity and significant binding free energy (MM-PBSA), along with favorable ADMET properties and stable intermolecular interactions with hotspots (including the ASN343 glycosylation site). The proposed hits are highly promising, as these are resultant of stringent in silico checkpoints, traditionally used, and are documented through contemporary literature. Hence, could serve as promising leads for subsequent experimental validations.

scholarly journals SARS-CoV19-2 Spike Protein Mutation Patterns: A Global Scenario

2020 ◽  
Author(s):  
Renukaradhya K. Math ◽  
Mallikarjun Goni ◽  
Palaksha K. Javaregowda ◽  
Ajay S. Khandagale ◽  
AjayKumar Oli
Keyword(s):  
Structure Prediction ◽  
Protein Sequences ◽  
Homology Model ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Biological Databases ◽  
Predominant Role ◽  
Protein Mutation ◽  
Geographical Regions

Analysis of SARS-CoV-2 spike protein sequences of over 19 countries from biological databases submitted around the globe was carried out with help of bioinformatics tools and structure prediction databases. Initial data analysis showed entry of virus into different geographic regions started in the month of January 2020. Meanwhile, alignment of spike protein sequences of SARS-CoV-2 isolates from China and other countries revealed a critical mutation of D614G. Surprisingly, mutation D614G was not seen in early samples submitted in the month of January but gradually it started appearing globally from the month of March 2020. However, the mutations of amino acids in the spike protein other than D614G exhibiting similar pI and altered polarity were found to be specific to geographical regions. Besides, prediction of homology model for interaction of spike protein showed predominant role of chain C of trimeric spike protein in adhering receptor binding domain (RBD) of human ACE2 receptor. Furthermore, the prediction of glycosylation points has revealed that there are about 20 N-glycosylation potential sites on spike protein. We believe that the information present here would not only help in thorough understanding of infectivity but also enhance the knowledge of the scientific community in developing prophylactics and/or therapeutics for SARS-CoV19-2 virus.

Lead Molecule Prediction and Characterization for Designing MERS-CoV 3C-like Protease Inhibitors: An In silico Approach

2018 ◽  
Vol 15 (1) ◽  
pp. 82-88 ◽  
Author(s):  
Md. Mostafijur Rahman ◽  
Md. Bayejid Hosen ◽  
M. Zakir Hossain Howlader ◽  
Yearul Kabir
Keyword(s):  
Binding Energy ◽  
Middle East ◽  
Virtual Screening ◽  
In Silico ◽  
Screening Method ◽  
Middle East Respiratory Syndrome ◽  
Cytochrome P450 Enzymes ◽  
Drug Molecules ◽  
Essential Enzyme ◽  
Reduced Toxicity

Background: 3C-like protease also called the main protease is an essential enzyme for the completion of the life cycle of Middle East Respiratory Syndrome Coronavirus. In our study we predicted compounds which are capable of inhibiting 3C-like protease, and thus inhibit the lifecycle of Middle East Respiratory Syndrome Coronavirus using in silico methods. </P><P> Methods: Lead like compounds and drug molecules which are capable of inhibiting 3C-like protease was identified by structure-based virtual screening and ligand-based virtual screening method. Further, the compounds were validated through absorption, distribution, metabolism and excretion filtering. Results: Based on binding energy, ADME properties, and toxicology analysis, we finally selected 3 compounds from structure-based virtual screening (ZINC ID: 75121653, 41131653, and 67266079) having binding energy -7.12, -7.1 and -7.08 Kcal/mol, respectively and 5 compounds from ligandbased virtual screening (ZINC ID: 05576502, 47654332, 04829153, 86434515 and 25626324) having binding energy -49.8, -54.9, -65.6, -61.1 and -66.7 Kcal/mol respectively. All these compounds have good ADME profile and reduced toxicity. Among eight compounds, one is soluble in water and remaining 7 compounds are highly soluble in water. All compounds have bioavailability 0.55 on the scale of 0 to 1. Among the 5 compounds from structure-based virtual screening, 2 compounds showed leadlikeness. All the compounds showed no inhibition of cytochrome P450 enzymes, no blood-brain barrier permeability and no toxic structure in medicinal chemistry profile. All the compounds are not a substrate of P-glycoprotein. Our predicted compounds may be capable of inhibiting 3C-like protease but need some further validation in wet lab.

Sign in / Sign up

Export Citation Format

Share Document