Development of an engineered ACE2 decoy for COVID-19 therapy. DOI Open Access
Toru Okamoto, Yumi Itoh, Tatsuya Suzuki

et al.

Uirusu, Journal Year: 2023, Volume and Issue: 73(2), P. 163 - 172

Published: Jan. 1, 2023

It has been passed four years since the pandemic caused by severe acute respiratory syndrome-2 (SARS-CoV-2) that began in 2019. Since June 2020, we have working on a project to develop therapeutic drug using receptor decoys, even though cannot predict how long will last or our daily lives be restricted. This decoy utilizes Angiotensin-converting enzyme 2 (ACE2), which is for SARS-CoV-2, and involves introducing mutations enhance its binding ability with spike protein of SARS-CoV-2. high-affinity ACE2, acting as protein, strategy inhibit viral infection expect effects replacing endogeneous ACE2 SARS-CoV-2 binds decoy. paper introduces development decoys progressed through collaborative research many researchers outside field virology.

Language: Английский

Applications of Cell-Based Protein Array Technology to Preclinical Safety Assessment of Biological Products DOI
Axel Vicart,

Cam Holland,

Kathryn Fraser

et al.

Toxicologic Pathology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

Off-target evaluation is essential in preclinical safety assessments of novel biotherapeutics, supporting lead molecule selection, endpoint selection toxicology studies, and regulatory requirements for first-in-human trials. interaction a therapeutic antibody derivatives has been historically assessed via the Tissue Cross-Reactivity (TCR) study, which candidate used as reagent immunohistochemistry (IHC) to assess binding panel human tissue sections. The TCR approach limited by performance an IHC reagent, often suboptimal outright infeasible. Furthermore, conditions typically poor vitro vivo translation lacks qualitative data identity putative off-targets limiting decisional value data. More recently, cell-based protein arrays (CBPA) that allow screening against large portion membrane proteome secretome have emerged complement, likely higher alternative, IHC-based off-target assessment. These identify specific interactions may be useful testing nontraditional antibody-based formats are unsuitable studies. This article presents overview CBPA technologies context assessment Selected case examples strategic considerations covering range different modalities presented.

Language: Английский

Citations

1
In vivo production of engineered ACE2 decoy protects lungs from SARS-CoV-2 infection DOI Creative Commons
Yuta Suzuki,

Takayuki Miyazaki,

Yoko Ida

et al.

Molecular Therapy — Nucleic Acids, Journal Year: 2025, Volume and Issue: 36(1), P. 102467 - 102467

Published: Jan. 29, 2025

Language: Английский

Citations

1
SARS-CoV-2 Omicron: Viral Evolution, Immune Evasion, and Alternative Durable Therapeutic Strategies DOI Creative Commons
Hailong Guo, Sha Ha, Jason Botten

et al.

Viruses, Journal Year: 2024, Volume and Issue: 16(5), P. 697 - 697

Published: April 28, 2024

Since the SARS-CoV-2 Omicron virus has gained dominance worldwide, its continual evolution with unpredictable mutations and patterns revoked all authorized immunotherapeutics. Rapid viral also necessitated several rounds of vaccine updates in order to provide adequate immune protection. It remains imperative understand how evolves into different subvariants causes escape as this could help reevaluate current intervention strategies mostly implemented clinics emergency measures counter pandemic and, importantly, develop new solutions. Here, we a review focusing on major events evolution, including features spike mutation that lead evasion against monoclonal antibody (mAb) therapy vaccination, suggest alternative durable options such ACE2-based experimental therapies superior mAbs address unprecedented virus. In addition, type unique virus-trapping molecules can zoonotic SARS coronaviruses, either from unknown animal hosts or established wild-life reservoirs SARS-CoV-2, even seasonal alpha coronavirus NL63 depends human ACE2 for infection.

Language: Английский

Citations

6
Antiviral covalent ACE2 vesicle spray DOI Creative Commons
Qian‐Fang Meng, Yu Han, Yu Liu

et al.

Published: March 1, 2025

Citations

0
Engineered DPP4 decoy confers broad-spectrum inhibition of MERS-CoV infection DOI Creative Commons

Keisuke Nishioka,

Yusuke Sakai, Daisuke Motooka

et al.

Published: March 1, 2025

Language: Английский

Citations

0
mRNA-encoded ACE2 decoy lipid nanoparticles for neutralizing SARS-CoV-2 variants DOI
Lays Cordeiro Guimarães, Heloísa Athaydes Seabra Ferreira, Pedro Pires Goulart Guimarães

et al.

Molecular Therapy — Nucleic Acids, Journal Year: 2025, Volume and Issue: 36(2), P. 102515 - 102515

Published: March 25, 2025

Citations

0
Development of Stable, Maleimide-Functionalized Peptidoliposomes Against SARS-CoV-2 DOI Open Access
Olga Michel, Aleksandra Kaczorowska, Lucyna Matusewicz

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1629 - 1629

Published: Feb. 14, 2025

Throughout the last 5 years, extensive research has been carried out towards development of effective treatments for coronavirus disease 2019 (COVID-19). Regardless worldwide efforts, only a few drugs have passed clinical trials, and there is still need to develop therapies, especially those who are particularly vulnerable severe course. Maleimide-functionalized liposomes proposed serve as platform immobilization, stabilization, delivery short peptide sequence with high affinity acute respiratory syndrome 2 (SARS-CoV-2). However, optimizations should be performed in order achieve features required reliable drug candidate, such homogeneity physical parameters their long-term stability. Here, we present step-by-step process maleimide-functionalized liposomes, which-once decorated SARS-CoV-2-binding peptide-could inhibit infection progress COVID-19. The main emphasis placed on defining optimal lipid composition formation conditions PEGylated liposomes. We propose that developed nanocarrier technology can used universal construction multiple antiviral agents.

Language: Английский

Citations

0
SARS-CoV-2 evolution has increased resistance to monoclonal antibodies and first-generation COVID-19 vaccines: Is there a future therapeutic role for soluble ACE2 receptors for COVID-19? DOI
Rohan Ameratunga,

A. M. Jordan,

Klaus Lehnert

et al.

Antiviral Research, Journal Year: 2024, Volume and Issue: 227, P. 105894 - 105894

Published: April 25, 2024

Language: Английский

Citations

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

Jenny Andrea Arévalo-Romero,

Gina López-Cantillo,

Sara Moreno-Jiménez

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(19), P. 10802 - 10802

Published: Oct. 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.

Language: Английский

Citations

2
Pathogen‐binding nanoparticles to inhibit host cell infection by heparan sulfate and sialic acid dependent viruses and protozoan parasites DOI Creative Commons
Adrian Najer

Smart Medicine, Journal Year: 2024, Volume and Issue: 3(2)

Published: March 1, 2024

Global health faces an immense burden from infectious diseases caused by viruses and intracellular protozoan parasites such as the coronavirus disease (COVID-19) malaria, respectively. These pathogens propagate through infection of human host cells. The first stage this cell mechanism is attachment, which typically involves interactions between agent surface components on membranes, specifically heparan sulfate (HS) and/or sialic acid (SA). Hence, nanoparticles (NPs) contain or mimic HS/SA that can directly bind to pathogen inhibit are emerging potential candidates for alternative anti-infection therapeutic strategy. NPs be prepared metals, soft matter (lipid, polymer, dendrimer), DNA, carbon-based materials among others designed include aspects multivalency, broad-spectrum activity, biocidal mechanisms, multifunctionality. This review provides overview anti-pathogen nanomedicines beyond drug delivery. Nanoscale inhibitors acting against obligate discussed. In future, availability broadly applicable nanotherapeutics would allow early tackling existing upcoming viral diseases. Invasion inhibitory could also provide urgently needed effective treatments parasitic infections.

Language: Английский

Citations

1