Target-specific peptides for BK virus agnoprotein identified through phage display screening: advancing antiviral therapeutics

Abstract BK virus is implicated in polyomavirus-associated nephropathy (PVAN) and hemorrhagic cystitis, particularly in kidney transplant recipients, affecting the functionality of the transplanted kidney and posing a risk of graft loss. Despite these challenges, specific antiviral drugs targeting B...

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Main Authors: Xiaofei Xing, Jingxian Han, Keke Wang, Fuyun Tian, CuiXia Jiang, Wei Liang, Lin Qi, Xin Yue, Yinhang Wen, Yuwei Hu, Hui Qiao
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-86439-4
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author Xiaofei Xing
Jingxian Han
Keke Wang
Fuyun Tian
CuiXia Jiang
Wei Liang
Lin Qi
Xin Yue
Yinhang Wen
Yuwei Hu
Hui Qiao
author_facet Xiaofei Xing
Jingxian Han
Keke Wang
Fuyun Tian
CuiXia Jiang
Wei Liang
Lin Qi
Xin Yue
Yinhang Wen
Yuwei Hu
Hui Qiao
author_sort Xiaofei Xing
collection DOAJ
description Abstract BK virus is implicated in polyomavirus-associated nephropathy (PVAN) and hemorrhagic cystitis, particularly in kidney transplant recipients, affecting the functionality of the transplanted kidney and posing a risk of graft loss. Despite these challenges, specific antiviral drugs targeting BK virus remain elusive. Agnoprotein, a small, positively charged protein encoded by the BK virus late gene, functions in the assembly, maturation, and release of the virus. Consequently, agnoprotein emerges as a promising target for potential anti-BK virus drugs. Utilizing phage display technology, we conducted screening to identify specific binding peptides against the agnoprotein. The primary objective of screening binding peptides is to utilize them to disrupt the virus’s life cycle, impeding its replication and transmission, thereby achieving antiviral effects. In the current experimental study, a combination of phage 7 peptide libraries and 12 peptide libraries was employed for screening purposes. Following four rounds of screening, seven positive phages demonstrating the ability to bind Agnoprotein were successfully isolated. Following ELISA validation, it was observed that the optical density (OD) values for Agnoprotein binding of the seven positive clones significantly exceeded three times the value of the negative control (NC). Subsequent analysis identified one 7-peptide and six 12-peptides within the binding peptides. Moreover, OD values of dodecapeptide phage clones bound to agnoprotein were generally higher than those of heptapeptide phage clones.In conclusion, our study demonstrates the successful identification of specific binding peptides against agnoprotein, a crucial component in the BK virus life cycle.
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spelling doaj-art-e7113f3c55f2434b8a4badbc70c231192025-01-26T12:24:26ZengNature PortfolioScientific Reports2045-23222025-01-0115111110.1038/s41598-025-86439-4Target-specific peptides for BK virus agnoprotein identified through phage display screening: advancing antiviral therapeuticsXiaofei Xing0Jingxian Han1Keke Wang2Fuyun Tian3CuiXia Jiang4Wei Liang5Lin Qi6Xin Yue7Yinhang Wen8Yuwei Hu9Hui Qiao10Department of Clinical Laboratory, Zhengzhou No. 7 People’s HospitalHenan Key Laboratory of Cardiac Remodeling and Transplantation, Zhengzhou NO.7 People’s HospitalHenan Key Laboratory of Cardiac Remodeling and Transplantation, Zhengzhou NO.7 People’s HospitalDepartment of Clinical Laboratory, Zhengzhou No. 7 People’s HospitalDepartment of Clinical Laboratory, Zhengzhou No. 7 People’s HospitalDepartment of Clinical Laboratory, Zhengzhou No. 7 People’s HospitalDepartment of Clinical Laboratory, Zhengzhou No. 7 People’s HospitalDepartment of Clinical Laboratory, Zhengzhou No. 7 People’s HospitalDepartment of Clinical Laboratory, Zhengzhou No. 7 People’s HospitalDepartment of Clinical Laboratory, Zhengzhou No. 7 People’s HospitalDepartment of Clinical Laboratory, Zhengzhou No. 7 People’s HospitalAbstract BK virus is implicated in polyomavirus-associated nephropathy (PVAN) and hemorrhagic cystitis, particularly in kidney transplant recipients, affecting the functionality of the transplanted kidney and posing a risk of graft loss. Despite these challenges, specific antiviral drugs targeting BK virus remain elusive. Agnoprotein, a small, positively charged protein encoded by the BK virus late gene, functions in the assembly, maturation, and release of the virus. Consequently, agnoprotein emerges as a promising target for potential anti-BK virus drugs. Utilizing phage display technology, we conducted screening to identify specific binding peptides against the agnoprotein. The primary objective of screening binding peptides is to utilize them to disrupt the virus’s life cycle, impeding its replication and transmission, thereby achieving antiviral effects. In the current experimental study, a combination of phage 7 peptide libraries and 12 peptide libraries was employed for screening purposes. Following four rounds of screening, seven positive phages demonstrating the ability to bind Agnoprotein were successfully isolated. Following ELISA validation, it was observed that the optical density (OD) values for Agnoprotein binding of the seven positive clones significantly exceeded three times the value of the negative control (NC). Subsequent analysis identified one 7-peptide and six 12-peptides within the binding peptides. Moreover, OD values of dodecapeptide phage clones bound to agnoprotein were generally higher than those of heptapeptide phage clones.In conclusion, our study demonstrates the successful identification of specific binding peptides against agnoprotein, a crucial component in the BK virus life cycle.https://doi.org/10.1038/s41598-025-86439-4BK virusKidney transplantAgnoproteinPhage display technologyPeptide drugs
spellingShingle Xiaofei Xing
Jingxian Han
Keke Wang
Fuyun Tian
CuiXia Jiang
Wei Liang
Lin Qi
Xin Yue
Yinhang Wen
Yuwei Hu
Hui Qiao
Target-specific peptides for BK virus agnoprotein identified through phage display screening: advancing antiviral therapeutics
Scientific Reports
BK virus
Kidney transplant
Agnoprotein
Phage display technology
Peptide drugs
title Target-specific peptides for BK virus agnoprotein identified through phage display screening: advancing antiviral therapeutics
title_full Target-specific peptides for BK virus agnoprotein identified through phage display screening: advancing antiviral therapeutics
title_fullStr Target-specific peptides for BK virus agnoprotein identified through phage display screening: advancing antiviral therapeutics
title_full_unstemmed Target-specific peptides for BK virus agnoprotein identified through phage display screening: advancing antiviral therapeutics
title_short Target-specific peptides for BK virus agnoprotein identified through phage display screening: advancing antiviral therapeutics
title_sort target specific peptides for bk virus agnoprotein identified through phage display screening advancing antiviral therapeutics
topic BK virus
Kidney transplant
Agnoprotein
Phage display technology
Peptide drugs
url https://doi.org/10.1038/s41598-025-86439-4
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