期刊
ANTIVIRAL RESEARCH
卷 173, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.antiviral.2019.104620
关键词
HCoV-229E; Coronavirus nucleocapsid; Cyclophilin A/B; Cyclophilin inhibitors; Broad-spectrum antiviral
资金
- Bundesministerium fuer Bildung und Forschung of the German Government [RAPID 01Kl1723C]
- German Center for Infection Research (DZIF, partner site Munich) [TTU EI 01.806]
- Friedrich-Baur-Stiftung
- Novartis AG (Basel, Switzerland)
The well-known immunosuppressive drug cyclosporin A inhibits replication of various viruses including coronaviruses by binding to cellular cyclophilins thus inactivating their cis-trans peptidyl-prolyl isomerase function. Viral nucleocapsid proteins are inevitable for genome encapsidation and replication. Here we demonstrate the interaction between the N protein of HCoV-229E and cyclophilin A, not cyclophilin B. Cyclophilin inhibitors abolish this interaction. Upon infection, cyclophilin A stays evenly distributed throughout the cell, whereas cyclophilin B concentrates at ER-bleb-like structures. We further show the inhibitory potential of non-immunosuppressive CsA derivatives Alisporivir, NIM811, compound 3 on HCoV-229E-GFP and -Luciferase replication in human Huh-7.5 hepatoma cells at 18 and 48 h time points post infection with EC50 s at low micromolar ranges. Thus, non-immunosuppressive CsA derivatives effectively inhibit HCoV-229E replication suggesting them as possible candidates for the treatment of HCoV infection. The interruption of interaction between CypA and N protein by CsA and its derivatives suggest a mechanism how CypA inhibitors suppress viral replication.
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