De novo design of covalent bonding peptides for target protein

hLife, Journal Year: 2024, Volume and Issue: unknown

Published: July 1, 2024

To rapidly develop hyper-stable inhibitors that bind specifically and covalently to functional proteins is critical for diagnostics therapeutics. Taking targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants as an example, we report a fast low-cost de novo design strategy on covalent bonding peptides toward the SARS-CoV-2 spike protein receptor-binding domain (RBD), hence blocking its interaction with human angiotensin-converting enzyme (hACE2). As proof-of-concept, peptide scaffolds built by ligating hotspot residues at hACE2-Omicron RBD interface were docked against RBD, then chemically modified designed predicting their reactivity using Amber ff14SB force field. Two (15- 16-mer peptides) equipped sulfonyl fluoride warheads bound conserved Y449 residue of via sulfur (VI) exchange (SuFEx) click chemistry. With permanent without dissociation, two blocked Omicron BA.2 pseudovirus infection IC50 values 1.07 μM 1.56 μM, respectively. Our approach greatly promotes discovery other evolving viruses, potentially applicable combat future viral outbreaks efficiently.

Language: Английский

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Lectins and lectibodies: potential promising antiviral agents

Cellular & Molecular Biology Letters, Journal Year: 2022, Volume and Issue: 27(1)

Published: May 13, 2022

Abstract In nature, lectins are widely dispersed proteins that selectively recognize and bind to carbohydrates glycoconjugates via reversible bonds at specific binding sites. Many viral diseases have been treated with due their wide range of structures, specificity for carbohydrates, ability carbohydrates. Through hemagglutination assays, these can be detected interacting various on the surface cells envelopes. This review discusses most robust rationally engineered versions, such as lectibodies, antiviral proteins. Fusion lectin antibody’s crystallizable fragment (Fc) immunoglobulin G (IgG) produces a molecule called “lectibody” act carbohydrate-targeting antibody. Lectibodies not only glycoproteins neutralize clear viruses or infected by but also perform Fc-mediated antibody effector functions. These functions include complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated (ADCC), phagocytosis (ADCP). addition entering host cells, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein S1 binds angiotensin-converting enzyme (ACE2) downregulates it type I interferons in way may lead lung disease. The SARS-CoV-2 human immunodeficiency virus (HIV) envelope heavily glycosylated, which could make them major target developing vaccines, diagnostic tests, therapeutic drugs. neutralization clearance glycans located (e.g., glycosylated protein).

Language: Английский

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Understanding Mutations in Human SARS-CoV-2 Spike Glycoprotein: A Systematic Review & Meta-Analysis

Viruses, Journal Year: 2023, Volume and Issue: 15(4), P. 856 - 856

Published: March 27, 2023

Genetic variant(s) of concern (VoC) SARS-CoV-2 have been emerging worldwide due to mutations in the gene encoding spike glycoprotein. We performed comprehensive analyses protein significant variant clade SARS-CoV-2, using data available on Nextstrain server. selected various mutations, namely, A222V, N439K, N501Y, L452R, Y453F, E484K, K417N, T478K, L981F, L212I, N856K, T547K, G496S, and Y369C for this study. These were chosen based their global entropic score, emergence, spread, transmission, location receptor binding domain (RBD). The relative abundance these was mapped with mutation D614G as a reference. Our suggest rapid emergence newer alongside D614G, reported during recent waves COVID-19 parts world. could be instrumentally imperative infectivity, virulence, host immune system’s evasion SARS-CoV-2. probable impact vaccine effectiveness, antigenic diversity, antibody interactions, stability, RBD flexibility, accessibility human cell ACE2 studied silico. Overall, present study can help researchers design next generation vaccines biotherapeutics combat infection.

Language: Английский

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mRNA: Vaccine or Gene Therapy? The Safety Regulatory Issues

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(13), P. 10514 - 10514

Published: June 22, 2023

COVID-19 vaccines were developed and approved rapidly in response to the urgency created by pandemic. No specific regulations existed at time they marketed. The regulatory agencies therefore adapted them as a matter of urgency. Now that pandemic emergency has passed, it is consider safety issues associated with this rapid approval. mode action mRNA should classify gene therapy products (GTPs), but have been excluded agencies. Some tests undergone produced non-compliant results terms purity, quality batch homogeneity. wide persistent biodistribution mRNAs their protein products, incompletely studied due classification vaccines, raises issues. Post-marketing studies shown passes into breast milk could adverse effects on breast-fed babies. Long-term expression, integration genome, transmission germline, passage sperm, embryo/fetal perinatal toxicity, genotoxicity tumorigenicity be light events reported pharmacovigilance databases. potential horizontal (i.e., shedding) also assessed. In-depth vaccinovigilance carried out. We would expect these controls required for future outside context

Language: Английский

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Viral inactivation by light

eLight, Journal Year: 2022, Volume and Issue: 2(1)

Published: Sept. 26, 2022

Abstract Nowadays, viral infections are one of the greatest challenges for medical sciences and human society. While antiviral compounds chemical inactivation remain inadequate, physical approaches based on irradiation provide new potentials prevention treatment infections, without risk drug resistance other unwanted side effects. Light across electromagnetic spectrum can inactivate virions using ionizing non-ionizing radiations. This review highlights anti-viral utility radiant methods from aspects radiation, including high energy ultraviolet, gamma ray, X-ray, neutron, photo-inactivation, lasers blue light.

Language: Английский

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SARS-CoV-2 VOCs, Mutational diversity and clinical outcome: Are they modulating drug efficacy by altered binding strength?

Genomics, Journal Year: 2022, Volume and Issue: 114(5), P. 110466 - 110466

Published: Aug. 27, 2022

The global COVID-19 pandemic continues due to emerging Severe Acute Respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC). Here, we performed comprehensive analysis in-house sequenced SARS-CoV-2 genome mutations dynamics in the patients infected with VOCs - Delta and Omicron, within Recovered Mortality patients. Statistical highlighted significant T4685A, N4992N, G5063S RdRp; T19R NTD spike; K444N N532H RBD spike, associated mortality. Mutations, T19I Q493R N440K spike were significantly Omicron We molecular docking for possible effect on binding Remdesivir. found that Remdesivir showed less efficacy mutant Spike protein both mortality compared recovered This indicates could have a modulatory drug which be disease outcome.

Language: Английский

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The emerging pandemic recent: SARS-CoV-2

Life Cycle, Journal Year: 2023, Volume and Issue: 3

Published: Jan. 22, 2023

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome 2 (SARS-CoV-2), induces coughing, vomiting, or fever. occurrence, duration, and severity of these symptoms vary from person to person, which makes the COVID-19 infection ranging those a mild cold death in cases. cause differences can be found individual characteristics patient. Age, former diseases patient, they medications took such characteristics. As SARS-CoV-2 affects lung, related lung as chronic obstructive pulmonary disease, cancer, cystic fibrosis, moderate asthma, hypertension, embolism are especially more dangerous human body when infected SARS-CoV-2. In this paper, through various methods including comparing mutant viruses subunits COVID-19, we aimed describe risk factors deterioration strain during pandemic.

Language: Английский

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Unveiling the Potential: High-Affinity aptamers for point of care detection of SARS-CoV-2 RBD protein and it’s validation in clinical samples

Chemical Engineering Journal, Journal Year: 2024, Volume and Issue: 493, P. 152841 - 152841

Published: June 5, 2024

Language: Английский

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Aptamers and Nanobodies as New Bioprobes for SARS-CoV-2 Diagnostic and Therapeutic System Applications

Biosensors, Journal Year: 2024, Volume and Issue: 14(3), P. 146 - 146

Published: March 15, 2024

The global challenges posed by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic have underscored critical importance of innovative and efficient control systems for addressing future pandemics. most effective way to is rapidly suppress spread virus through early detection using a rapid, accurate, easy-to-use diagnostic platform. In biosensors that use bioprobes, binding affinity molecular recognition elements (MREs) primary factor determining dynamic range sensing Furthermore, sensitivity relies mainly on bioprobe quality with sufficient functionality. This comprehensive review investigates aptamers nanobodies recently developed as advanced MREs SARS-CoV-2 therapeutic applications. These bioprobes might be integrated into organic bioelectronic materials devices, promising enhanced specificity. offers valuable insights advancing biosensing technologies infectious disease diagnosis treatment new bioprobes.

Language: Английский

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Bioactive Compositions of Cinnamon (Cinnamomum verum J. Presl) Extracts and Their Capacities in Suppressing SARS-CoV-2 Spike Protein Binding to ACE2, Inhibiting ACE2, and Scavenging Free Radicals

Journal of Agricultural and Food Chemistry, Journal Year: 2023, Volume and Issue: 71(12), P. 4890 - 4900

Published: March 20, 2023

Cinnamon (Cinnamomum verum J. Presl) bark and its extracts are popular ingredients added to food supplement products. It has various health effects, including potentially reducing the risk of coronavirus disease-2019 (COVID-19). In our study, bioactives in cinnamon water ethanol were chemically identified, their potential suppressing SARS-CoV-2 spike protein–angiotensin-converting enzyme 2 (ACE2) binding, ACE2 availability, scavenging free radicals was investigated. Twenty-seven twenty-three compounds tentatively identified extracts, respectively. Seven compounds, saccharumoside C, two emodin–glucuronide isomers, physcion–glucuronide type-A proanthocyanidin hexamers, first reported cinnamon. suppressed binding protein inhibited activity a dose-dependent manner. extract had total phenolic content 36.67 mg gallic acid equivalents (GAE)/g radical activities against HO• 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) cation (ABTS•+) 1688.85 882.88 μmol Trolox (TE)/g, which significantly higher than those at 24.12 GAE/g 583.12 210.36 TE/g. The 2,2-diphenyl-1-picrylhydrazyl (DPPH•) lower that extract. present study provides new evidence reduces infection COVID-19 development.

Language: Английский

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