Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production
| Autor: | Suthinee Soponpong, Chatchai Tayapiwatana, Umpa Yasamut, Supachai Sakkhachornphop, Thanathat Pamonsupornwichit, Kanokporn Sornsuwan, Tanawan Samleerat Carraway, Weeraya Thongkhum |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Anti-HIV Agents
Cell Survival viruses Virus Replication medicine.disease_cause Giant Cells Biochemistry Microbiology Article Cell Line Serine ankyrin medicine capsid Humans Ankyrin Designed Ankyrin Repeat Proteins Amino Acid Sequence Tyrosine Cell Shape Molecular Biology HIV-1 assembly chemistry.chemical_classification Mutation Syncytium Cell Death Cell Membrane virus diseases QR1-502 Cell biology chemistry Capsid DARPin CD4 Antigens HIV-1 anti-HIV-1 molecule Viral load HIV-1 drug resistance Protein Binding Subcellular Fractions |
| Zdroj: | Biomolecules, Vol 11, Iss 1437, p 1437 (2021) Biomolecules Volume 11 Issue 10 |
| 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: | OpenAIRE |
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