Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production

Autor: Kanokporn Sornsuwan, Weeraya Thongkhum, Thanathat Pamonsupornwichit, Tanawan Samleerat Carraway, Suthinee Soponpong, Supachai Sakkhachornphop, Chatchai Tayapiwatana, Umpa Yasamut
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Biomolecules, Vol 11, Iss 10, p 1437 (2021)
Druh dokumentu: article
ISSN: 2218-273X
DOI: 10.3390/biom11101437
Popis: Previously, a designed ankyrin repeat protein, AnkGAG1D4, was generated for intracellular targeting of the HIV-1 capsid domain. The efficiency was satisfactory in interfering with the HIV assembly process. Consequently, improved AnkGAG1D4 binding affinity was introduced by substituting tyrosine (Y) for serine (S) at position 45. However, the intracellular anti-HIV-1 activity of AnkGAG1D4-S45Y has not yet been validated. In this study, the performance of AnkGAG1D4 and AnkGAG1D4-S45Y in inhibiting wild-type HIV-1 and HIV-1 maturation inhibitor-resistant replication in SupT1 cells was evaluated. HIV-1 p24 and viral load assays were used to verify the biological activity of AnkGAG1D4 and AnkGAG1D4-S45Y as assembly inhibitors. In addition, retardation of syncytium formation in infected SupT1 cells was observed. Of note, the defense mechanism of both ankyrins did not induce the mutation of target amino acids in the capsid domain. The present data show that the potency of AnkGAG1D4-S45Y was superior to AnkGAG1D4 in interrupting either HIV-1 wild-type or the HIV maturation inhibitor-resistant strain.
Databáze: Directory of Open Access Journals
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