Mutations in SARS-CoV-2 structural proteins: a global analysis

Virology Journal, Journal Year: 2022, Volume and Issue: 19(1)

Published: Dec. 18, 2022

Abstract Background Emergence of new variants mainly concerns (VOC) is caused by mutations in main structural proteins severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, we aimed to investigate the among SARS-CoV-2 globally. Methods We analyzed samples amino-acid sequences (AASs) for envelope (E), membrane (M), nucleocapsid (N), and spike (S) from declaration 2019 (COVID-19) as pandemic January 2022. The presence location were then investigated aligning reference sequence categorizing them based on frequency continent. Finally, related human genes with viral discovered, their interactions reported. Results results indicated that most relative E, M, N, S AASs occurred regions 7 14, 66 88, 164 205, 508 635 AAs, respectively. frequent T9I, I82T, R203M/R203K, D614G. D614G was mutation all six geographical areas. Following D614G, L18F, A222V, E484K, N501Y, respectively, ranked protein Besides, A-kinase Anchoring Protein 8 Like (AKAP8L) shown linkage unit between E cluster genes. Conclusion Screening can help scientists introduce better drug vaccine development strategies.

Language: Английский

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Domperidone inhibits dengue virus infection by targeting the viral envelope protein and nonstructural protein 1

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 30, 2025

Dengue is a mosquito-borne disease caused by dengue virus (DENV) infection, which remains major public health concern worldwide owing to the lack of specific treatments or antiviral drugs available. This study investigated potential repurposing domperidone, an antiemetic and gastrokinetic agent, control DENV infection. Domperidone was identified pharmacophore-based virtual screening as small molecule that can bind both viral envelope (E) nonstructural protein 1 (NS1) DENV. Molecular dynamics (MD) simulations surface plasmon resonance (SPR) analysis were subsequently performed determine interactions domperidone with E NS1 proteins their binding affinity. Treatment immortalized human hepatocyte-like cells (imHC) could inhibit production secretion in dose-dependent manner following infection serotype 2. These inhibitory effects mediated reduction RNA replication expression, but not interference entry into oligomerization. The suppression observed across all four serotypes varying degrees between different strains. findings from our suggest target-based for modulating

Language: Английский

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Drug repurposing against main protease and RNA-dependent RNA polymerase of SARS-CoV-2 using molecular docking, MM-GBSA calculations and molecular dynamics

Structural Chemistry, Journal Year: 2022, Volume and Issue: 33(5), P. 1553 - 1567

Published: June 27, 2022

Language: Английский

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Exploring the Fatty Acid Binding Pocket in the SARS-CoV-2 Spike Protein – Confirmed and Potential Ligands

Journal of Chemical Information and Modeling, Journal Year: 2023, Volume and Issue: 63(23), P. 7282 - 7298

Published: Nov. 22, 2023

Severe Acute Respiratory syndrome 2 (SARS-CoV-2) is a respiratory virus responsible for coronavirus disease 19 (COVID-19) and the still ongoing unprecedented global pandemic. The key viral protein cell infection spike glycoprotein, surface-exposed fusion that both recognizes mediates entry into host cells. Within fatty acid binding pocket (FABP) was confirmed, with crystallization of linoleic (LA) occupying well-defined site. Importantly, when occupied by acid, an inactive conformation stabilized, recognition hindered. In this review, we discuss ligands reported so far site, correlating their activity predicted through in silico studies antispike experimental activity, assessed either assays or cell-infection assays. LA first confirmed ligand, cocrystallized cryo-EM structure protein, resulting increased stability protein. next identified lifitegrast, also experimentally as ligand antiviral suggesting potential diverse chemical scaffolds to bind Finally, SPC-14 although no inhibition were performed. 20 describing small-molecule compounds vitro inhibitory against spike-ACE2 interaction cell-based When considering all assays, good overall occupation should be complemented ability make direct interactions, hydrophilic hydrophobic, amino residues defining surface. Among active compounds, long flexible carbon chains are recurrent, retinoids capable FABP, bulkier systems affecting fitness. Compounds able site high affinity have stabilize SARS-CoV-2 therefore reduce virus's infect new Since conserved highly pathogenic human coronaviruses, including MERS-CoV SARS-CoV, effect could exploited development agents, broad-spectrum anticoronavirus activity.

Language: Английский

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Hesperidin, a Potential Antiviral Agent against SARS-CoV-2: The Influence of Citrus Consumption on COVID-19 Incidence and Severity in China

Medicina, Journal Year: 2024, Volume and Issue: 60(6), P. 892 - 892

Published: May 28, 2024

This review examines hesperidin, a citrus bioflavonoid, as potential antiviral agent against SARS-CoV-2. The COVID-19 pandemic has demanded an urgent need to search for effective compounds, including those of natural origin, such hesperidin. provides comprehensive analysis the chemical properties, bioavailability and mechanisms particularly its efficacy A databases, PubMedPico, Scopus Web Science, was conducted using specific keywords criteria in accordance with PRISMA (Re-porting Items Systematic Reviews Meta-Analysis) guidelines between 2020 2024. Of 207 articles, 37 were selected review. key aspect is correlation vitro, silico clinical studies on effects hesperidin epidemiological data consumption China during 2020–2024. importance integrating laboratory findings actual patterns better understand role mitigating highlighted, attempt made analyze examine association juice source incidence severity example. identifies consistencies discrepancies experimental data, highlighting correlate two fields Challenges limitations interpreting results future research perspectives this area are discussed. aim bridge gap evidence contribute understanding their correlation.

Language: Английский

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Ganoderma microsporum immunomodulatory protein acts as a multifunctional broad-spectrum antiviral against SARS-CoV-2 by interfering virus binding to the host cells and spike-mediated cell fusion

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 155, P. 113766 - 113766

Published: Sept. 28, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible that has caused over 6 million fatalities. SARS-CoV-2 variants with spike mutations are frequently endowed strong capability to escape vaccine-elicited protection. Due this characteristic, broad-spectrum inhibitor against infection urgently demanded. Ganoderma microsporum immunomodulatory protein (GMI) was previously reported alleviate of through ACE2 downregulation whereas the impact GMI on virus itself less understood. Our study aims determine effects pseudovirus and more detailed mechanisms inhibition infection.ACE2-overexpressing HEK293T cells (HEK293T/ACE2) pseudoviruses carrying were used in vitro. Infectivity evaluated by fluorescence microscopy flow cytometry. Fusion rate mediated examined split fluorescent /luciferase systems. The interactions investigated immunoprecipitation immunoblotting.GMI broadly blocked various cell lines. effectively inhibited pseudotyped viruses different emerged variants, including Delta Omicron strains, HEK293T/hACE2 cells. In cell-free infection, dominantly impeded binding spike-bearing ACE2-expressing cell-to-cell fusion model, could efficiently inhibit spike-mediated syncytium without requirement downregulation.GMI, an FDA-approved dietary ingredient, acts as multifunctional antiviral become promising candidate for preventing or treating associated diseases.

Language: Английский

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The Microalgal Diatoxanthin Inflects the Cytokine Storm in SARS-CoV-2 Stimulated ACE2 Overexpressing Lung Cells

Antioxidants, Journal Year: 2022, Volume and Issue: 11(8), P. 1515 - 1515

Published: Aug. 3, 2022

Contact between SARS-CoV-2 and human lung cells involves the viral spike protein angiotensin-converting enzyme 2 (ACE2) receptor on epithelial cells, latter being strongly involved in regulation of inflammation as well blood pressure homeostasis. infection is characterized by a strong inflammatory response defined "cytokine storm". Among recent therapeutic approaches against targeting dramatic reaction, some natural products are promising. Diatoms microalgae able to produce bioactive secondary metabolites, such xanthophyll diatoxanthin (Dt). The aim this study demonstrate anti-inflammatory effects Dt A549-hACE2 cell line, exploring its interaction with ACE2 receptor, depicting role inhibiting cytokine storm induced glycoprotein. Results showed that enhanced metabolism, e.g., percent metabolically active enzymatic activity. Moreover, affected glycoprotein-exposed decreasing interleukin-6 production increasing interleukin-10 release. upregulated genes encoding for interferon pathway related antiviral defense proteins belonging innate immunity response. potential interest new agent treatment and/or prevention severe syndrome postulated.

Language: Английский

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In silico screening of some compounds derived from the desert medicinal plant Rhazya stricta for the potential treatment of COVID-19

Scientific Reports, Journal Year: 2022, Volume and Issue: 12(1)

Published: July 1, 2022

Abstract The latest coronavirus pandemic (SARS-CoV-2) poses an exceptional threat to human health and society worldwide. spike (S) protein, which is required for viral–host cell penetration, might be considered a promising suitable target treatment. In this study, we utilized the nonalkaloid fraction of medicinal plant Rhazya stricta computationally investigate its antiviral activity against SARS-CoV-2. Molecular docking molecular dynamics simulations were main tools used examine binding interactions compounds isolated by HPLC analysis. Ceftazidime was as reference control, showed high potency SARS-CoV-2 receptor domain (RBD) in vitro study. five (CID:1, CID:2, CID:3, CID:4, CID:5) exhibited remarkable affinities − 8.9; 8.7; 4, 5, 8.5 kcal/mol) compared control compound (− 6.2 kcal/mol). MD over period 200 ns further corroborated that certain occurred with nonalkaloidal retained their positions within RBD active site. CID:5 demonstrated stability less variance, while CID:1 CID:3 stable than ceftazidime. average number hydrogen bonds formed per timeframe CID:1, (0.914, 0.451, 1.566, 1.755, respectively) greater ceftazidime (0.317). total free energy calculations revealed interacted more strongly residues (CID:1 = 68.8, CID:2 71.6, 74.9, CID:4 75.4, 60.9 kJ/mol) 34.5 kJ/mol). drug-like properties selected relatively similar those ceftazidime, toxicity predictions categorized these into toxic classes. Structural similarity functional group analyses suggested presence H-acceptor atoms, electronegative acidic oxygen groups, nitrogen atoms amide or aromatic groups common among lowest affinities. conclusion, silico work predicts first time potential using R. treatment strategy viral entry.

Language: Английский

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Structure based Drug Designing Approaches in SARS-CoV-2 Spike Inhibitor Design

Current Topics in Medicinal Chemistry, Journal Year: 2022, Volume and Issue: 22(29), P. 2396 - 2409

Published: Nov. 1, 2022

Abstract: The COVID-19 outbreak and the pandemic situation have hastened research commu-nity to design a novel drug vaccine against its causative organism, SARS-CoV-2. spike glycoprotein present on surface of this pathogenic organism plays an immense role in viral entry antigenicity. Hence, it is considered important target design. Several three-dimensional crystal structures SARS-CoV-2 protein been identified de-posited Protein DataBank during period. This accelerated com-puter-aided designing, especially field structure-based designing. review summarizes various approaches applied pro-tein findings. Specifically, focused different such as mo-lecular docking, high-throughput virtual screening, molecular dynamics simulation, repurpos-ing, target-based pharmacophore modelling screening. These structural ligands datasets FDA-approved drugs, small chemi-cal compounds, chemical libraries, databases, analogs, natural which resulted prediction inhibitors, spike-ACE-2 interface allosteric inhibitors.

Language: Английский

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In Silico Therapeutic Study: The Next Frontier in the Fight against SARS-CoV-2 and Its Variants

Drugs and Drug Candidates, Journal Year: 2024, Volume and Issue: 3(1), P. 54 - 69

Published: Jan. 5, 2024

COVID-19 has claimed around 7 million lives (from December 2019–November 2023) worldwide and continues to impact global health. SARS-CoV-2, the virus causing disease, is characterized by a high rate of mutations, which contributes its rapid spread, virulence, vaccine escape. While several vaccines have been produced minimize severity coronavirus, diverse treatment regimens approved US FDA under Emergency Use Authorization (EUA), SARS-CoV-2 viral mutations continue derail efforts scientists as emerging variants evade recommended therapies. Nonetheless, computational models exist that offer an opportunity for swift development new drugs or repurposing old drugs. In this review, we focus on use various virtual screening techniques like homology modeling, molecular docking, dynamics simulations, QSAR, pharmacophore etc., in therapeutics against major (Alpha, Beta, Gamma, Delta, Omicron). The results promising from computer-aided drug design (CADD) studies suggesting potential compounds variants. Hence, silico therapeutic represent transformative approach holds great promise advancing our fight ever-evolving landscape

Language: Английский

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