Evolutionary progression of collective mutations in Omicron sub-lineages towards efficient RBD-hACE2: allosteric communications between and within viral and human proteins DOI Creative Commons
Victor Barozi, Adrienne L. Edkins, Özlem Taştan Bishop

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2022, Номер unknown

Опубликована: Авг. 8, 2022

Abstract The interaction between the Spike (S) protein of SARS-CoV-2 and human angiotensin converting enzyme 2 (hACE2) is essential for infection, a target neutralizing antibodies. Consequently, selection mutations in S expected to be driven by impact on with hACE2 antibody escape. Here, first time, we systematically characterized collective effects each Omicron sub-lineages (BA.1, BA.2, BA.3 BA.4) both viral receptor binding domain (RBD) using post molecular dynamics studies dynamic residue network (DRN) analysis. Our analysis suggested that sub-lineage result altered physicochemical properties change conformational flexibility compared reference structure, may contribute We also observed changes substrate groove some sub-lineages. Notably, identified unique allosteric communication paths complex formed DRN metrics betweenness centrality eigencentrality hubs, originating from RBD core traversing motif N-terminal active site. showed proteins due mutations. Taken together, these data suggest progressive evolution towards more efficient which account increased transmissibility variants.

Язык: Английский

Targeting Spike Protein: Modified Antibody for Broad-Spectrum Binding to Coronaviruses: An In Silico Study DOI Open Access

Rai RC

Virology & Immunology Journal, Год журнала: 2023, Номер 7(3), С. 1 - 15

Опубликована: Июль 7, 2023

An antibody-mediated immune response against the Spike protein is one of potential ways to target SARS-CoV-2 virus. The discovery a highly effective vaccine or an antiviral drug that specifically targets viral entry its replication pathway, are commonly pursued as way combat COVID-19-like situation. virus has RNA genetic material, which known for high mutation rate. This makes efficiency and efficacy it suboptimal later due continuous mutations in epitope region was evident case spread Omicron (B.1.1.529) variant. Here we tested in-silico approach towards finding antibody recognise bind across most variants. We achieved this by altering sequences VDJ heavy light chains natural human (Wuhan, PDB ID: 7BWJ). first antibodies be studied published along with crystal structure during mid2020, have ability neutralize Wuhan isolate. Iterative substitutions were induced 7BWJ sequence different combinations. After 28 iterations, found variants comparatively higher docking score. also showed many members Coronaviruses.

Язык: Английский

Процитировано

4
Review from host and guest approach to new frontiers nutraceuticals in the era of COVID-19 DOI Creative Commons
Matteo Micucci, Silvia Gioacchini, Melissa Baggieri

и другие.

Future Foods, Год журнала: 2024, Номер 9, С. 100303 - 100303

Опубликована: Янв. 21, 2024

COVID-19 continues to claim victims in the world, especially among elderly subjects and people suffering from chronic-degenerative pathologies, like cardiovascular diseases. Several vaccines drugs have been developed mitigate infection spread its deleterious consequences. However, emergence of new variants requires identification solutions deal with challenging mutations. In this context, investigation phytocomplexes related compounds used folk medicine culinary purposes may lead unfold nutraceuticals endowed antiviral, cardioprotective properties. We described several vegetal extracts secondary metabolites that hit most important viral host targets bind them. The connection between SARS-CoV-2 diseases were also outlined, as well potentials for their mitigation. review provides both an entry point researchers area, a comprehensive overview further natural products presented.

Язык: Английский

Процитировано

1
A review of the role of graphene-based nanomaterials in tackling challenges posed by the COVID-19 pandemic DOI
Sachin Sharma Ashok Kumar, Shahid Bashir,

M. Pershaanaa

и другие.

Microbial Pathogenesis, Год журнала: 2024, Номер 197, С. 107059 - 107059

Опубликована: Окт. 22, 2024

Язык: Английский

Процитировано

1
Evolutionary progression of collective mutations in Omicron sub-lineages towards efficient RBD-hACE2: Allosteric communications between and within viral and human proteins DOI Creative Commons
Victor Barozi, Adrienne L. Edkins, Özlem Taştan Bishop

и другие.

Computational and Structural Biotechnology Journal, Год журнала: 2022, Номер 20, С. 4562 - 4578

Опубликована: Янв. 1, 2022

The interaction between the Spike (S) protein of SARS-CoV-2 and human angiotensin converting enzyme 2 (hACE2) is essential for infection, a target neutralizing antibodies. Consequently, selection mutations in S expected to be driven by impact on with hACE2 antibody escape. Here, first time, we systematically characterized collective effects each Omicron sub-lineages (BA.1, BA.2, BA.3 BA.4) both viral receptor binding domain (RBD) using post molecular dynamics studies dynamic residue network (DRN) analysis. Our analysis suggested that sub-lineage result altered physicochemical properties change conformational flexibility compared reference structure, may contribute We also observed changes substrate groove some sub-lineages. Notably, identified unique allosteric communication paths complex formed DRN metrics betweenness centrality eigencentrality hubs, originating from RBD core traversing motif N-terminal active site. showed proteins due mutations. Taken together, these data suggest progressive evolution towards more efficient which account increased transmissibility variants.

Язык: Английский

Процитировано

6
Identification of potential Indonesian marine invertebrate bioactive compounds as TMPRSS2 and SARS-CoV-2 Omicron spike protein inhibitors through computational screening DOI Creative Commons

Haviani Rizka Nurcahyaningtyas,

Alfrina Irene,

Joko Tri Wibowo

и другие.

Arabian Journal of Chemistry, Год журнала: 2023, Номер 16(9), С. 104984 - 104984

Опубликована: Май 17, 2023

The coronavirus pandemic led to the announcement of a worldwide health emergency. SARS-CoV-2 Omicron variant, which swiftly spread worldwide, has fueled existing challenges. Appropriate medication is necessary avoid severe disease. human TMPRSS2 and spike protein, are required for viral entry into host phase, were identified as target proteins through computational screening. Structure-based virtual screening; molecular docking; absorption, distribution, metabolism, excretion, toxicity (ADMET) analysis; dynamics simulation methods applied protein inhibitors. Bioactive marine invertebrates from Indonesia employed test ligands. Camostat nafamostat (co-crystal) utilized reference ligands against TMPRSS2, whereas mefloquine was used ligand protein. Following docking simulation, we found that acanthomanzamine C remarkable effectiveness Compared camostat (-8.25 kcal/mol), (-6.52 (-6.34 binds with binding energies −9.75 kcal/mol −9.19 kcal/mol, respectively. Furthermore, slight variances in MD demonstrated consistent after initial 50 ns. These results highly valuable search treatment infection.

Язык: Английский

Процитировано

3
A computational study on the molecular mechanisms of panduratin A as a potential inhibitor on SARS-CoV-2 protein targets DOI Creative Commons

Patamalai Boonserm,

Pongsak Khunrae, Thana Sutthibutpong

и другие.

Heliyon, Год журнала: 2023, Номер 9(1), С. e12780 - e12780

Опубликована: Янв. 1, 2023

Panduratin A from Boesebergia rotunda was recently reported as a potent anti-SARS-CoV-2 compound. However, the molecular mechanisms underlying inhibition by and its target remained unclear. Molecular docking calculations were performed between panduratin five important proteins, i.e., main protease (Mpro), papain-like (PLpro), receptor binding domain (RBD) of spike RNA-dependent-RNA-polymerase (RdRp), 2′-O-methyltransferase (MTase). The estimated free energy interaction networks extracted best mode for each complex suggested that MTase most probable inhibition. To further validate ability to inhibit MTase, dynamics (MD) simulations A-MTase complex, in comparison with another sinefungin positive control. Chemical features compared their contribution binding. It found both molecules could bind S-Adenosyl methionine (SAM) pocket prevent SAM entrance co-substrate, which eventually halt function MTase. Despite slightly weaker energy, equilibrated positional at closer distance active sites. Therefore, this study proposed possible A, along inhibition, prompting future vitro verification.

Язык: Английский

Процитировано

2
Docking Studies and Molecular Dynamics Simulations of Potential Inhibitors from the Brown Seaweed Sargassum polycystum (Phaeophyceae) against PLpro of SARS-CoV-2 DOI Creative Commons
Asmi Citra Malina A.R. Tassakka, Israini Wiyulanda Iskandar, Jamaluddin Fitrah Alam

и другие.

BioTech, Год журнала: 2023, Номер 12(2), С. 46 - 46

Опубликована: Июнь 11, 2023

The COVID-19 disease is a major problem affecting human health all over the world. Consequently, researchers have been trying to find solutions treat this pandemic-scale disease. Even if there are vaccines and approved drugs that could decrease spread of pandemic, multidisciplinary approaches still needed identify new small molecules as alternatives combat COVID-19, especially those from nature. In study, we employed computational by screening 17 natural compounds tropical brown seaweed Sargassum polycystum known anti-viral properties benefit health. This study assessed some products bound PLpro SARS-CoV-2. By employing pharmacophore molecular docking, these S. showed remarkable scores for protein targets with competitive compared X-ray crystallography ligands well-known antiviral compounds. provides insightful information advanced further in vitro examination clinical investigation drug development prospects abundant yet underexploited seaweeds.

Язык: Английский

Процитировано

2
5-Aminolevulinic acid antiviral efficacy against SARS-CoV-2 omicron variant in vitro DOI Creative Commons
Mya Myat Ngwe Tun, Takaya Sakura, Yasuteru Sakurai

и другие.

Tropical Medicine and Health, Год журнала: 2022, Номер 50(1)

Опубликована: Апрель 27, 2022

The coronavirus disease 2019 (COVID 19) pandemic continues to pose a threat global health. severe acute respiratory syndrome 2 (SARS-CoV-2) Omicron variant (B.1.1.529) has spread rapidly worldwide and became dominant in many countries. A natural 5-aminolevulinic acid (5-ALA) with sodium ferrous citrate (SFC) demonstrated antiviral activity Wuhan, Alpha, Beta, Gamma, Delta variants of SARS-CoV-2 infections vitro. In this study, we report 5-ALA, 5-ALA SFC led IC50 329 765/191, respectively after infection Our finding suggests that could be used as drug candidate treat infected patients.

Язык: Английский

Процитировано

3
Cheminformatics-enhanced discovery of therapeutic agents targeting isocitrate lyase in Mycobacterium tuberculosis infections DOI
Aftab Alam, Mohammed H. Alqarni, Bader S. Alotaibi

и другие.

Journal of Biomolecular Structure and Dynamics, Год журнала: 2024, Номер unknown, С. 1 - 18

Опубликована: Сен. 18, 2024

Tuberculosis (TB) is a global health challenge; therefore, there an urgent requirement to develop novel and more effective anti-TB therapeutic. This study targeted the isocitrate lyase (ICL) protein due its pivotal role in pathogenicity of

Язык: Английский

Процитировано

0
The inhibitory effect of vitamins on O micron virus via targeting the ACE2 receptor. In silico analysis DOI Creative Commons
Khadidja Belkheir,

Nora Laref

Journal of King Saud University - Science, Год журнала: 2023, Номер 36(2), С. 103082 - 103082

Опубликована: Дек. 26, 2023

The wide and rapid spread of epidemics like Covid 19, highlighted the need for development effective solutions. In present work, a therapeutic approach based on use vitamins against Omicron variant spike was investigated through bioinformatics tools. inhibitory effect A, B2, B3, C, E, D, K1 K7 were tested in silico molecular docking dynamic simulation four ACE2 grid boxes binding specifically proteins 7T9K, 7T9L, 7WBL 7WBP. study showed that K1, D E bind strongly efficiently to receptor. High scores with low energies strong interactions crucial amino acids residues generally noted these vitamins. analysis 100ns best docked complexes using Gromacs tools at temperature 300 K allowed screening vitamin A-grid2, E- grid4, K1-grid2 D-grid 2 as most stable compared rest systems. These findings indicate could interact directly receptor blocking this way its host.

Язык: Английский

Процитировано

1