In vitro and in vivo validation of the antiviral effect of hCypA against SARS-CoV-2 via binding to the RBD of spike protein

Copyright © 2024 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved..

The novel coronavirus disease 2019 has stimulated the rapid development of new biological therapeutics to inhibit SARS-CoV-2 infection; however, this remains a challenging task. In a previous study using structural analysis, we revealed that human cyclophilin A inhibits the entry of SARS-CoV-2 into host cells by interfering with the interaction of the receptor-binding domain of the spike protein with angiotensin-converting enzyme 2 on the host cell surface, highlighting its potential for antiviral therapy. For a comprehensive experimental validation, in this study, we verified the antiviral effects of human cyclophilin A against SARS-CoV-2, including its variants, using in vitro assays and experiments on an in vivo mouse model. Human cyclophilin A demonstrated a highly effective antiviral effect, with an 85% survival rate upon SARS-CoV-2 infection. It also reduced viral titers, inflammation in the lungs and brain, and cytokine release in the serum, suggesting a controlled immune response and potentially faster recovery. Overall, our study provides insights into the potential of human cyclophilin A as a therapeutic agent against SARS-CoV-2, which should guide future clinical trials that might provide an additional therapeutic option for patients.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - year:2024

Enthalten in:

Molecular therapy : the journal of the American Society of Gene Therapy - (2024) vom: 25. März

Sprache:

Englisch

Beteiligte Personen:

Shin, Woo-Ri [VerfasserIn]
Kim, Do-Young [VerfasserIn]
Kim, Sang Yong [VerfasserIn]
Ahn, Gna [VerfasserIn]
Park, Dae-Young [VerfasserIn]
Min, Jiho [VerfasserIn]
Ahn, Ji-Young [VerfasserIn]
Kim, Yang-Hoon [VerfasserIn]

Links:

Volltext

Themen:

Antiviral
COVID-19
Cyclophilin A
Cytokine storm
Inflammation
Journal Article
SARS-CoV-2
Spike protein
Therapeutic

Anmerkungen:

Date Revised 07.04.2024

published: Print-Electronic

Citation Status Publisher

doi:

10.1016/j.ymthe.2024.03.029

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM370221753