| Author | Costa-Tuna, Andreia | |
| Author | Chaves, Otávio Augusto | |
| Author | Almeida, Zaida L. | |
| Author | Cunha, Rita S. | |
| Author | Pina, João | |
| Author | Serpa, Carlos | |
| Access date | 2024-04-30T12:58:23Z | |
| Available date | 2024-04-30T12:58:23Z | |
| Document date | 2024 | |
| Citation | COSTA-TUNA, Andreia et al. Profiling the interaction between human serum albumin and clinically relevant HIV reverse transcriptase inhibitors. Viruses, v. 16, n. 4, p. 1-17, 22 Mar. 2024. | |
| ISSN | 1999-4915 | |
| URI | https://www.arca.fiocruz.br/handle/icict/63760 | |
| Description | Produção científica do Laboratório de Imunofarmacologia. | pt_BR |
| Sponsorship | This research was funded by Fundação para a Ciência e a Tecnologia (FCT—Portuguese Agency for Scientific Research) through the projects UIDB/00313/2020 (https://doi.org/10.54499/UIDB/00313/2020) and UIDP/00313/2020 (https://doi.org/10.54499/UIDP/00313/2020). Otávio Augusto Chaves also thanks FCT for his PhD fellowship 2020.07504.BD. João Pina acknowledges FCT for the funding through the program CEECINST/00152/2018/CP1570/CT0012 (https://doi.org/10.54499/CEECINST/00152/2018/CP1570/CT0012). | |
| Language | eng | en_US |
| Publisher | MDPI | |
| Rights | open access | |
| Title | Profiling the interaction between human serum albumin and clinically relevant HIV reverse transcriptase inhibitors | en_US |
| Type | Article | |
| DOI | 10.3390/v16040491 | |
| Abstract | Tenofovir (TFV) is the active form of the prodrugs tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF), both clinically prescribed as HIV reverse transcriptase inhibitors. The biophysical interactions between these compounds and human serum albumin (HSA), the primary carrier of exogenous compounds in the human bloodstream, have not yet been thoroughly characterized. Thus, the present study reports the interaction profile between HSA and TFV, TDF, and TAF via UV–Vis, steady-state, and time-resolved fluorescence techniques combined with isothermal titration calorimetry (ITC) and in silico calculations. A spontaneous interaction in the ground state, which does not perturb the microenvironment close to the Trp-214 residue, is classified as weak. In the case of HSA/TFV and HSA/TDF, the binding is both enthalpically and entropically driven, while for HSA/TAF, the binding is only entropically dominated. The binding constant (Kₐ) and thermodynamic parameters obtained via ITC assays agree with those obtained using steady-state fluorescence quenching measurements, reinforcing the reliability of the data. The small internal cavity known as site I is probably the main binding pocket for TFV due to the low steric volume of the drug. In contrast, most external sites (II and III) can better accommodate TAF due to the high steric volume of this prodrug. The cross-docking approach corroborated experimental drug-displacement assays, indicating that the binding affinity of TFV and TAF might be impacted by the presence of different compounds bound to albumin. Overall, the weak binding capacity of albumin to TFV, TDF, and TAF is one of the main factors for the low residence time of these antiretrovirals in the human bloodstream; however, positive cooperativity for TAF and TDF was detected in the presence of some drugs, which might improve their residence time (pharmacokinetic profile). | en_US |
| Affilliation | Universidade de Coimbra. Faculdade de Ciências e Tecnologia. Departamento de Química. Instituto de Ciência Molecular. Centro de Química. Coimbra, Portugal. | |
| Affilliation | Universidade de Coimbra. Faculdade de Ciências e Tecnologia. Departamento de Química. Instituto de Ciência Molecular. Centro de Química. Coimbra, Portugal / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisa, Inovação e Vigilância em COVID-19 e Emergências Sanitárias. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Universidade de Coimbra. Faculdade de Ciências e Tecnologia. Departamento de Química. Instituto de Ciência Molecular. Centro de Química. Coimbra, Portugal. | |
| Affilliation | Universidade de Coimbra. Faculdade de Ciências e Tecnologia. Departamento de Química. Instituto de Ciência Molecular. Centro de Química. Coimbra, Portugal. | |
| Affilliation | Universidade de Coimbra. Faculdade de Ciências e Tecnologia. Departamento de Química. Instituto de Ciência Molecular. Centro de Química. Coimbra, Portugal. | |
| Affilliation | Universidade de Coimbra. Faculdade de Ciências e Tecnologia. Departamento de Química. Instituto de Ciência Molecular. Centro de Química. Coimbra, Portugal. | |
| Subject | Prodrugs | en_US |
| Subject | HIV reverse transcriptase inhibitors | en_US |
| Subject | Tenofovir | en_US |
| Subject | HSA binding | en_US |
| Subject | Spectroscopy techniques | en_US |
| Subject | In silico calculations | en_US |
| Subject | Isothermal titration calorimetry | en_US |
| e-ISSN | 1999-4915 | |
| xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |
| xmlui.metadata.dc.subject.ods | 09 Indústria, inovação e infraestrutura | |
