An engineered miniACE2 protein secreted by mesenchymal stromal cells effectively neutralizes multiple SARS-CoV- 2 variants in vitro

Molecular Medicine, Год журнала: 2025, Номер 31(1)

Опубликована: Апрель 23, 2025

Abstract SARS-CoV- 2 continues to evolve, producing novel Omicron subvariants through recombinant lineages that acquire new mutations, undermining existing antiviral strategies. The viral fitness and adaptive potential of present significant challenges emergency treatments, particularly monoclonal antibodies, which demonstrate reduced efficacy with the emergence each variant. Consequently, immunocompromised individuals, who are more susceptible severe manifestations COVID- 19 face heightened risks critical complications mortality, remain vulnerable in absence effective treatments. To develop translational approaches can benefit this at-risk population establish broader therapeutic strategies applicable across variants, we previously designed engineered silico miniACE2 decoys (designated BP2, BP9, BP11). These demonstrated promising neutralizing subvariants. In study, leveraged mesenchymal stromal cells (MSCs) for tissue repair immunomodulation lung injuries used these as a platform secretion BP2. Our innovative assays, were conducted BP2 protein secreted into culture supernatant BP2-MSCs, 2, including development advanced platforms holds promise scalability effectively mitigate impact 19, contributing resilient treatment against evolving landscape variants.

Язык: Английский

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In Silico Design of miniACE2 Decoys with In Vitro Enhanced Neutralization Activity against SARS-CoV-2, Encompassing Omicron Subvariants

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(19), С. 10802 - 10802

Опубликована: Окт. 8, 2024

The COVID-19 pandemic has overwhelmed healthcare systems and triggered global economic downturns. While vaccines have reduced the lethality rate of SARS-CoV-2 to 0.9% as October 2024, continuous evolution variants remains a significant public health challenge. Next-generation medical therapies offer hope in addressing this threat, especially for immunocompromised individuals who experience prolonged infections severe illnesses, contributing viral evolution. These cases increase risk new emerging. This study explores miniACE2 decoys novel strategy counteract variants. Using silico design molecular dynamics, blocking proteins (BPs) were developed with stronger binding affinity receptor-binding domain multiple than naturally soluble human ACE2. BPs expressed E. coli tested vitro, showing promising neutralizing effects. Notably, BP9 exhibited an average IC50 4.9 µg/mL across several variants, including Wuhan strain, Mu, Omicron BA.1, BA.2 low demonstrates potent ability BP9, indicating its efficacy at concentrations.Based on these findings, emerged therapeutic candidate combating evolving thereby positioning it potential emergency biopharmaceutical.

Язык: Английский

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Epidemiological and immunological characteristics of middle-aged and elderly people in housing estates after Omicron BA.5 wave in Jinan, China

Heliyon, Год журнала: 2024, Номер 10(19), С. e38382 - e38382

Опубликована: Сен. 25, 2024

A great number of COVID-19 patients was caused by Omicron BA.5 subvariant between December 2022 and January 2023 after the end zero-COVID-19 policy in China. In this study, we clarified epidemiological immunological characteristics 457 enrolled middle-aged elderly population two housing estates wave. total 89.9 % (411/457) individuals have suffered infection, among which 78.1 (321/411) were symptomatic. The more likely to show fatigue had longer symptomatic period than that post infection. XBB BA.2.86 subvariants extensively escaped immunity elicited level neutralizing antibody mostly affected vaccination doses rather underlying disease status these participants. It is very important strengthen investigation immune resistance assessment for control emerging SARS-CoV-2 variants.

Язык: Английский

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Protocol to evaluate virus-specific CD4+ and CD8+ T cell responses by spectral flow cytometry

STAR Protocols, Год журнала: 2024, Номер 5(4), С. 103497 - 103497

Опубликована: Дек. 1, 2024

T cell responses play an important role in viral clearance and prevention of infection. Here, we present a protocol to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific using spectral flow cytometry. We describe steps for peripheral blood mononuclear (PBMC) thawing stimulation with SARS-CoV-2 spike peptide pools. then detailed procedures confining, staining, fixation. This has potential application cytometry on other virus-specific responses. For complete details the use execution this protocol, please refer Zhao et al.

Язык: Английский

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