Capivasertib restricts SARS-CoV-2 cellular entry: a potential clinical application for COVID-19

Autor: Zhijian Cao, Xugang Li, Wanhong Liu, Yingliang Wu, Fang Sun, Jean-Marc Sabatier, Cédric Annweiler, Yingqiu Xie, Jiyuan Xu, Chenglin Mu, Hang Fai Kwok
Přispěvatelé: Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)
Rok vydání: 2021
Předmět:
MESH: Virus Internalization
viruses
Akt inhibitor
Applied Microbiology and Biotechnology
Chlorocebus aethiops
AKT inhibitor
Phosphatidylinositol 3-Kinases
MESH: Chlorocebus aethiops
Neoplasms
MESH: COVID-19
MESH: Animals
MESH: Neoplasms
skin and connective tissue diseases
biology
integumentary system
3. Good health
[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology
antiviral activity
MESH: Pyrroles
Research Paper
2019-20 coronavirus outbreak
Coronavirus disease 2019 (COVID-19)
Proto-Oncogene Proteins c-akt
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
MESH: Receptor Cross-Talk
MESH: Vero Cells
capivasertib
MESH: Computer Simulation
Animals
Humans
MESH: SARS-CoV-2
Computer Simulation
Pyrroles
Molecular Biology
Vero Cells
Ecology
Evolution
Behavior and Systematics

MESH: Humans
MESH: Proto-Oncogene Proteins c-akt
SARS-CoV-2
fungi
COVID-19
Cell Biology
Receptor Cross-Talk
Virus Internalization
biology.organism_classification
Virology
COVID-19 Drug Treatment
body regions
PI3K/AKT pathway
Pyrimidines
MESH: Pyrimidines
[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology
Vero cell
Commentary
[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Developmental Biology
Zdroj: International Journal of Biological Sciences
International Journal of Biological Sciences, Ivyspring International Publisher, 2021, 17 (9), pp.2348-2355. ⟨10.7150/ijbs.57810⟩
International Journal of Biological Sciences, 2021, 17 (9), pp.2348-2355. ⟨10.7150/ijbs.57810⟩
ISSN: 1449-2288
DOI: 10.7150/ijbs.57810⟩
Popis: International audience; Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has led to more than 150 million infections and about 3.1 million deaths up to date. Currently, drugs screened are urgently aiming to block the infection of SARS-CoV-2. Here, we explored the interaction networks of kinase and COVID-19 crosstalk, and identified phosphoinositide 3-kinase (PI3K)/AKT pathway as the most important kinase signal pathway involving COVID-19. Further, we found a PI3K/AKT signal pathway inhibitor capivasertib restricted the entry of SARS-CoV-2 into cells under non-cytotoxic concentrations. Lastly, the signal axis PI3K/AKT/FYVE finger-containing phosphoinositide kinase (PIKfyve)/PtdIns(3,5)P2 was revealed to play a key role during the cellular entry of viruses including SARS-CoV-2, possibly providing potential antiviral targets. Altogether, our study suggests that the PI3K/AKT kinase inhibitor drugs may be a promising anti-SARS-CoV-2 strategy for clinical application, especially for managing cancer patients with COVID-19 in the pandemic era.
Databáze: OpenAIRE