Universität zu Köln

Alkhashrom, Sewar, Kicuntod, Jintawee, Stillger, Katharina, Luetzenburg, Tamara, Anzenhofer, Christian, Neundorf, Ines ORCID: 0000-0001-6450-3991, Marschall, Manfred and Eichler, Jutta ORCID: 0000-0001-6683-9456 (2022). A Peptide Inhibitor of the Human Cytomegalovirus Core Nuclear Egress Complex. Pharmaceuticals, 15 (9). BASEL: MDPI. ISSN 1424-8247

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Abstract

The replication of human cytomegalovirus (HCMV) involves a process termed nuclear egress, which enables translocation of newly formed viral capsids from the nucleus into the cytoplasm. The HCMV core nuclear egress complex (core NEC), a heterodimer of viral proteins pUL50 and pUL53, is therefore considered a promising target for new antiviral drugs. We have recently shown that a 29-mer peptide presenting an N-terminal alpha-helical hook-like segment of pUL53, through which pUL53 interacts with pUL50, binds to pUL50 with high affinity, and inhibits the pUL50-pUL53 interaction in vitro. Here, we show that this peptide is also able to interfere with HCMV infection of cells, as well as with core NEC formation in HCMV-infected cells. As the target of the peptide, i.e., the pUL50-pUL53 interaction, is localized at the inner nuclear membrane of the cell, the peptide had to be equipped with translocation moieties that facilitate peptide uptake into the cell and the nucleus, respectively. For the resulting fusion peptide (NLS-CPP-Hook), specific cellular and nuclear uptake into HFF cells, as well as inhibition of infection with HCMV, could be demonstrated, further substantiating the HCMV core NEC as a potential antiviral target.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Alkhashrom, Sewar UNSPECIFIED UNSPECIFIED UNSPECIFIED Kicuntod, Jintawee UNSPECIFIED UNSPECIFIED UNSPECIFIED Stillger, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Luetzenburg, Tamara UNSPECIFIED UNSPECIFIED UNSPECIFIED Anzenhofer, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Neundorf, Ines UNSPECIFIED orcid.org/0000-0001-6450-3991 UNSPECIFIED Marschall, Manfred UNSPECIFIED UNSPECIFIED UNSPECIFIED Eichler, Jutta UNSPECIFIED orcid.org/0000-0001-6683-9456 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-665737
DOI:	10.3390/ph15091040
Journal or Publication Title:	Pharmaceuticals
Volume:	15
Number:	9
Date:	2022
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	1424-8247
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CELL-PENETRATING PEPTIDES; HIV-1 TAT PEPTIDES; PROTEINS PUL50; MEMBRANE Multiple languages Chemistry, Medicinal; Pharmacology & Pharmacy Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/66573