دورية أكاديمية

Amuvatinib Blocks SARS-CoV-2 Infection at the Entry Step of the Viral Life Cycle

التفاصيل البيبلوغرافية
العنوان: Amuvatinib Blocks SARS-CoV-2 Infection at the Entry Step of the Viral Life Cycle
المؤلفون: Trang T. X. Huynh, Thuy X. Pham, Gun-Hee Lee, Jae-Bong Lee, Sung-Geun Lee, Dongseob Tark, Yun-Sook Lim, Soon B. Hwang
المصدر: Microbiology Spectrum, Vol 11, Iss 3 (2023)
بيانات النشر: American Society for Microbiology, 2023.
سنة النشر: 2023
المجموعة: LCC:Microbiology
مصطلحات موضوعية: SARS-CoV-2, COVID-19, amuvatinib, tyrosine kinase, therapeutic agent, Microbiology, QR1-502
الوصف: ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). SARS-CoV-2 propagation is mediated by the protein interaction between viral proteins and host cells. Tyrosine kinase has been implicated in viral replication, and hence, it has become a target for developing antiviral drugs. We have previously reported that receptor tyrosine kinase inhibitor blocks the replication of hepatitis C virus (HCV). In the present study, we investigated two receptor tyrosine kinase-specific inhibitors, amuvatinib and imatinib, for their potential antiviral efficacies against SARS-CoV-2. Treatment with either amuvatinib or imatinib displays an effective inhibitory activity against SARS-CoV-2 propagation without an obvious cytopathic effect in Vero E6 cells. Notably, amuvatinib exerts a stronger antiviral activity than imatinib against SARS-CoV-2 infection. Amuvatinib blocks SARS-CoV-2 infection with a 50% effective concentration (EC50) value ranging from ~0.36 to 0.45 μM in Vero E6 cells. We further demonstrate that amuvatinib inhibits SARS-CoV-2 propagation in human lung Calu-3 cells. Using pseudoparticle infection assay, we verify that amuvatinib blocks SARS-CoV-2 at the entry step of the viral life cycle. More specifically, amuvatinib inhibits SARS-CoV-2 infection at the binding-attachment step. Moreover, amuvatinib exhibits highly efficient antiviral activity against emerging SARS-CoV-2 variants. Importantly, we demonstrate that amuvatinib inhibits SARS-CoV-2 infection by blocking ACE2 cleavage. Taken together, our data suggest that amuvatinib may provide a potential therapeutic agent for the treatment of COVID-19. IMPORTANCE Tyrosine kinase has been implicated in viral replication and has become an antiviral drug target. Here, we chose two well-known receptor tyrosine kinase inhibitors, amuvatinib and imatinib, and evaluated their drug potencies against SARS-CoV-2. Surprisingly, amuvatinib displays a stronger antiviral activity than imatinib against SARS-CoV-2. Amuvatinib blocks SARS-CoV-2 infection by inhibiting ACE2 cleavage and the subsequent soluble ACE2 receptor. All these data suggest that amuvatinib may be a potential therapeutic agent in SARS-CoV-2 prevention for those experiencing vaccine breakthroughs.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2165-0497
Relation: https://doaj.org/toc/2165-0497
DOI: 10.1128/spectrum.05105-22
URL الوصول: https://doaj.org/article/5a48daac5d894da284da852e0950ef88
رقم الأكسشن: edsdoj.5a48daac5d894da284da852e0950ef88
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:21650497
DOI:10.1128/spectrum.05105-22