Application of pseudovirus system in the development of vaccine, antiviral-drugs, and neutralizing antibodies

Microbiological Research, Journal Year: 2022, Volume and Issue: 258, P. 126993 - 126993

Published: Feb. 16, 2022

Language: Английский

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Sub‐lineages of the SARS‐CoV‐2 Omicron variants: Characteristics and prevention

MedComm, Journal Year: 2022, Volume and Issue: 3(3)

Published: Aug. 16, 2022

Abstract Since the start of coronavirus disease 2019 (COVID‐19) pandemic, new variants severe acute respiratory syndrome 2 (SARS‑CoV‑2) have emerged, accelerating spread virus. Omicron was defined by World Health Organization in November 2021 as fifth “variant concern” after Alpha, Beta, Gamma, and Delta. In recent months, has become main epidemic strain. Studies shown that carries more mutations than Delta, wild‐type, facilitating immune escape its transmission. This review focuses on variant's origin, transmission, biological features, subvariants, mutations, escape, vaccination, detection methods. We also discuss appropriate preventive therapeutic measures should be taken to address challenges posed variant. is valuable guide surveillance, prevention, development vaccines other therapies for variants. It desirable develop a efficient vaccine against variant take effective constrain promote public health.

Language: Английский

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Development of a screening platform to discover natural products active against SARS-CoV-2 infection using lung organoid models

Biomaterials Research, Journal Year: 2023, Volume and Issue: 27(1)

Published: Feb. 9, 2023

Natural products can serve as one of the alternatives, exhibiting high potential for treatment and prevention COVID-19, caused by SARS-CoV-2. Herein, we report a screening platform to test antiviral efficacy natural product library against SARS-CoV-2 verify their activity using lung organoids. Since is classified risk group 3 pathogen, drug assay must be performed in biosafety level (BSL-3) laboratory. To circumvent this limitation, pseudotyped viruses (PVs) have been developed replacements live We PVs containing spikes from Delta Omicron variants improved infection an angiotensin-converting enzyme 2 (ACE2)-dependent manner. Human induced pluripotent stem cells (hiPSCs) derived organoids were generated therapeutic products. Flavonoids our had strong Delta- or Omicron-spike-containing without affecting cell viability. aimed develop strategies discover dual function either inhibiting at beginning cycle reducing spike stability following infection. When are already infected with virus, active flavonoids degradation protein exerted anti-inflammatory effects. Further experiments confirmed that organoid models. This will open new paths providing promising standard system discovering novel leads help candidates clinical investigation therapeutics COVID-19.

Language: Английский

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Variant-specific interactions at the plasma membrane: Heparan sulfate’s impact on SARS-CoV-2 binding kinetics

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 10, 2024

Abstract The worldwide spread of SARS-CoV-2 has been characterised by the emergence several variants concern (VOCs) presenting an increasing number mutations in viral genome. spike glycoprotein, responsible for engaging receptor ACE2, exhibits highest density mutations, suggesting ongoing evolution to optimize entry. However, previous studies focussed on isolated molecular interactions, neglecting intricate composition plasma membrane and interplay between attachment factors. Our study explores role avidity complexity modulating virus-host binding kinetics during early stages entry original Wuhan strain three VOCs: Omicron BA.1, Delta, Alpha. We employ fluorescent liposomes decorated with from VOCs as virion mimics single-particle tracking native supported lipid bilayers derived pulmonary Calu-3 cells. findings reveal increase affinity multivalent bond cell surface driven increased association rate. show that heparan sulfate (HS), a sulfated glycosaminoglycan commonly expressed cells’ membrane, plays central interaction we observe shift its screening ACE2 important factor Omicron. This is caused ∼10-fold Omicron’s HS compared strain, shown using atomic force microscopy-based single-molecule spectroscopy. results importance coreceptors, particularly HS, modulation VOCs. highlight transition variants’ strategy towards use initial docking site, which likely shaping tropism infection upper airways, milder symptoms, higher transmissibility.

Language: Английский

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Developing Pseudovirus-Based Neutralization Assay against Omicron-Included SARS-CoV-2 Variants

Viruses, Journal Year: 2022, Volume and Issue: 14(6), P. 1332 - 1332

Published: June 18, 2022

The global spread of SARS-CoV-2 and its variants poses a serious threat to human health worldwide. Recently, the emergence Omicron has presented new challenge prevention control COVID-19 pandemic. A convenient reliable in vitro neutralization assay is an important method for validating efficiency antibodies, vaccines, other potential drugs. Here, we established effective based on pseudovirus carrying full-length spike (S) protein HIV-1 backbone, with luciferase reporter gene inserted into non-replicate genome. key parameters packaging were optimized, including ratio S expression plasmids HIV backbone collection time Alpha, Beta, Gamma, Kappa, particles. was validated using several approved or developed monoclonal underscoring that can escape some neutralizing such as REGN10987 REGN10933, while S309 ADG-2 still function reduced capability. capacity convalescent plasma from patients Wuhan tested against these pseudoviruses, revealing immune evasion Omicron. Our work practical pseudovirus-based variants, which be conducted safely under biosafety level-2 (BSL-2) conditions, this will promising tool studying characterizing vaccines therapeutic candidates Omicron-included variants.

Language: Английский

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High-throughput detection of neutralizing antibodies to SARS-CoV-2 variants using flow cytometry

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 9, 2023

Abstract Detecting neutralizing antibodies (NAbs) to SARS-CoV-2 variants is crucial for controlling COVID-19 spread. We developed a high-throughput assay the broad systematic examination of NAbs eleven variants, which include D614G, Alpha, Beta, Gamma, Delta, Kappa, and Omicron sub-lineages BA.1-BA.5. The cost-effective, reliable, 35-fold more sensitive than Luminex technology, can new during evolution. Importantly, our results highly correlated with commercial IgG serological (R = 0.89), FDA-approved cPass sVNT 0.93), pseudivirus-based 0.96, R 0.66, 0.65) live virus based neutralization 0.79, 0.64) . Using this platform, we constructed comprehensive overview interactions between variants’ Spike trimer proteins ACE2 receptors, identified polyclonal Ab activity. Furthermore, when compared D614G variant, found that serum elicited by third dose vaccine demonstrated decreased inhibition multiple including Gamma (0.94×), Alpha (0.91×), Delta Beta (0.81×), Kappa BA.2 (0.44×), BA.1 (0.43×), BA.3 (0.41×), BA.5 (0.35×) BA.4 (0.33×), in cohort 56 vaccinated individuals. Altogether, proteomics platform proves be an effective tool detect population aid development future vaccines vaccination strategies.

Language: Английский

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Targeting Viral and Cellular Cysteine Proteases for Treatment of New Variants of SARS-CoV-2

Viruses, Journal Year: 2024, Volume and Issue: 16(3), P. 338 - 338

Published: Feb. 22, 2024

The continuous emergence of SARS-CoV-2 variants caused the persistence COVID-19 epidemic and challenged effectiveness existing vaccines. viral proteases are most attractive targets for developing antiviral drugs. In this scenario, our study explores use HIV-1 protease inhibitors against SARS-CoV-2. An in silico screening a library identified four anti-HIV compounds able to interact with 3CLpro Thus, vitro studies were designed evaluate their potential We employed pseudovirus technology simulate, highly safe manner, adsorption alpha (α-SARS-CoV-2) omicron (ο-SARS-CoV-2) inhibitory mechanism selected cell–virus interaction. results reported mild activity PLpro, but efficient effects on internalization both mediated by cathepsin B/L. Our findings provide insights into feasibility using drugs exhibiting other viruses host required entry.

Language: Английский

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An efficient plasmid-based system for the recovery of recombinant vesicular stomatitis virus encoding foreign glycoproteins

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: June 25, 2024

Abstract Viral glycoproteins mediate entry into host cells, thereby dictating range and pathogenesis. In addition, they constitute the principal target of neutralizing antibody responses, making them important antigens in vaccine development. Recombinant vesicular stomatitis virus (VSV) encoding foreign can provide a convenient safe surrogate system to interrogate function, evolution, antigenicity viral from viruses that are difficult manipulate or those requiring high biosafety level containment. However, production recombinant VSV be technically challenging. this work, we present an efficient robust plasmid-based for glycoproteins. We validate using different families, including arenaviruses, coronaviruses, hantaviruses, as well highlight their utility studying effects mutations on fitness. Overall, methods described herein facilitate study both native serve basis VSV-based vaccines.

Language: Английский

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Molecular Engineering of Virus Tropism

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(20), P. 11094 - 11094

Published: Oct. 15, 2024

Engineered viral vectors designed to deliver genetic material specific targets offer significant potential for disease treatment, safer vaccine development, and the creation of novel biochemical research tools. Viral tropism, specificity a virus infecting particular host, is often modified in recombinant viruses achieve precise delivery, minimize off-target effects, enhance transduction efficiency, improve safety. Key factors influencing tropism include surface protein interactions between host-cell, availability host-cell machinery replication, host immune response. This review explores current strategies modifying by altering their proteins. We provide an overview recent advancements targeting non-enveloped (adenovirus adeno-associated virus) enveloped (retro/lentivirus, Rabies, Vesicular Stomatitis Virus, Herpesvirus) cell types. Additionally, we discuss approaches, such as rational design, directed evolution, silico machine learning-based methods, generating AAV variants with desired use chimeric envelope proteins pseudotyping viruses. Finally, highlight applications these challenges future directions engineering tropism.

Language: Английский

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Strictinin, a Major Ingredient in Yunnan Kucha Tea Possessing Inhibitory Activity on the Infection of Mouse Hepatitis Virus to Mouse L Cells

Molecules, Journal Year: 2023, Volume and Issue: 28(3), P. 1080 - 1080

Published: Jan. 21, 2023

Theacrine and strictinin of Yunnan Kucha tea prepared from a mutant variety wild Pu’er plants were two major ingredients responsible for the anti-influenza activity. As COVID-19 outbreak is still lurking, developing safe cost-effective therapeutics an urgent need. This study aimed to evaluate effects these compounds on infection mouse hepatitis virus (MHV), β-coronavirus serving as surrogate SARS-CoV. Treatment with (100 μM), but not theacrine, completely eliminated MHV infection, indicated by pronounced reduction in plaque formation, nucleocapsid protein expression, progeny production MHV. Subsequently, time-of-drug addition protocol, including pre-, co-, or post-treatment, was exploited further possible mechanism antiviral activity mediated strictinin, remdesivir, potential drug treatment SARS-CoV-2, used positive control against infection. The results showed that all three treatments remdesivir (20 μM) blocked In contrast, no significant effect observed when cells pre-treated prior while inhibition introduced upon viral adsorption (co-treatment) after entry (post-treatment). Of note, compared co-treatment group, inhibitory more striking post-treatment group. These indicate suppresses multiple mechanisms; it possibly interferes also critical step(s) Evidently, significantly inhibited might be suitable ingredient protection coronavirus

Language: Английский

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