Integrating different approaches for the identification of new disruptors of HIV-1 capsid multimerization
Human Immunodeficiency Virus (HIV) belongs to the Lentivirus genus, Retroviridae family, enveloped by a lipid bilayer within which the capsid protein encases the viral genome, reverse transcriptase, and integrase proteins, key components for viral replication. Viral capsid has been linked to key ear...
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| مؤلفون آخرون: | , , , , , , , |
| التنسيق: | article |
| اللغة: | الإنجليزية |
| منشور في: |
2025
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| الموضوعات: | |
| الوصول للمادة أونلاين: | https://hdl.handle.net/20.500.12381/5273 https://doi.org/10.1016/j.bbrc.2025.151572 |
| الوسوم: |
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| _version_ | 1868889981002448896 |
|---|---|
| author | Artía, Zoraima |
| author2 | Guillon, Christophe Robert, Xavier Granzella, Maximiliano Segovia, Ana Clara Truong, Ha H Álvarez, Guzmán Corvo, Ileana Randall-Carlevaro, Lía |
| author2_role | author author author author author author author author |
| author_browse | Artía, Zoraima Corvo, Ileana Granzella, Maximiliano Guillon, Christophe Randall-Carlevaro, Lía Robert, Xavier Segovia, Ana Clara Truong, Ha H Álvarez, Guzmán |
| author_facet | Artía, Zoraima Guillon, Christophe Robert, Xavier Granzella, Maximiliano Segovia, Ana Clara Truong, Ha H Álvarez, Guzmán Corvo, Ileana Randall-Carlevaro, Lía |
| author_role | author |
| collection | REDI |
| dc.creator.none.fl_str_mv | Artía, Zoraima Guillon, Christophe Robert, Xavier Granzella, Maximiliano Segovia, Ana Clara Truong, Ha H Álvarez, Guzmán Corvo, Ileana Randall-Carlevaro, Lía |
| dc.date.none.fl_str_mv | 2025-10-28T18:32:42Z 2025-05-12 2026-05-12T03:30:12Z |
| dc.identifier.none.fl_str_mv | https://hdl.handle.net/20.500.12381/5273 FCE_3_2022_1_172494 https://doi.org/10.1016/j.bbrc.2025.151572 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | Elsevier |
| dc.relation.none.fl_str_mv | https://hdl.handle.net/20.500.12381/5280 https://hdl.handle.net/20.500.12381/5284 https://hdl.handle.net/20.500.12381/5285 https://hdl.handle.net/20.500.12381/5286 https://hdl.handle.net/20.500.12381/5305 |
| dc.rights.none.fl_str_mv | Acceso abierto info:eu-repo/semantics/openAccess Reconocimiento-NoComercial-SinObraDerivada 4.0 Internacional. (CC BY-NC-ND) El artículo no se encuentra en una revista de acceso abierto 2026-05-12 |
| dc.source.none.fl_str_mv | Biochemical and Biophysical Research Communications reponame:REDI instname:Agencia Nacional de Investigación e Innovación instacron:Agencia Nacional de Investigación e Innovación |
| dc.subject.none.fl_str_mv | Artificial intelligence Capsid Drug development HIV-1 Screening Ciencias Médicas y de la Salud Medicina Básica Bioquímica y Biología Molecular Medicina Química Farmacología y Farmacia |
| dc.title.none.fl_str_mv | Integrating different approaches for the identification of new disruptors of HIV-1 capsid multimerization |
| dc.type.none.fl_str_mv | Artículo info:eu-repo/semantics/article Aceptado info:eu-repo/semantics/acceptedVersion |
| description | Human Immunodeficiency Virus (HIV) belongs to the Lentivirus genus, Retroviridae family, enveloped by a lipid bilayer within which the capsid protein encases the viral genome, reverse transcriptase, and integrase proteins, key components for viral replication. Viral capsid has been linked to key early and late stages of viral infection, including nuclear entry, promoting reverse transcription and assembly of new viral particles within target TCD4+ lymphocytes. Effective treatments for HIV involve multi drug therapy, which can reduce the patient's viral load to undetectable values, thus avoiding the appearance of Acquired Immunodeficiency Syndrome (AIDS). In this study, a conserved region of the HIV capsid protein was selected and 84 compounds were selected from a massive Artificial Intelligence-based virtual screening as potential HIV capsid assembly disruptors. In vitro screening was performed using recombinant protein and complemental approaches were carried out to identify molecules capable of interfering with capsid multimerization. From this work, 9 compounds were selected as successful to continue through in cell and toxicity assays for further development as possible HIV treatments. In conclusion, this work demonstrates the efficiency of integrating rational computational and experimental methodologies to identify new candidates as potential antiviral molecules. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | anni_20a7741d1985d00f86d70bbfd7bb7c1b |
| identifier_str_mv | FCE_3_2022_1_172494 |
| instacron_str | Agencia Nacional de Investigación e Innovación |
| institution | Agencia Nacional de Investigación e Innovación |
| instname_str | Agencia Nacional de Investigación e Innovación |
| language | eng |
| network_acronym_str | anni |
| network_name_str | oai-lr-anni |
| oai_identifier_str | oai:redi.anii.org.uy:20.500.12381/5273 |
| publishDate | 2025 |
| publishDateSort | 2025 |
| publisher.none.fl_str_mv | Elsevier |
| reponame_str | REDI |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | Acceso abierto Reconocimiento-NoComercial-SinObraDerivada 4.0 Internacional. (CC BY-NC-ND) El artículo no se encuentra en una revista de acceso abierto 2026-05-12 |
| spelling | Integrating different approaches for the identification of new disruptors of HIV-1 capsid multimerizationArtía, ZoraimaGuillon, ChristopheRobert, XavierGranzella, MaximilianoSegovia, Ana ClaraTruong, Ha HÁlvarez, GuzmánCorvo, IleanaRandall-Carlevaro, LíaArtificial intelligenceCapsidDrug developmentHIV-1ScreeningCiencias Médicas y de la SaludMedicina BásicaBioquímica y Biología MolecularMedicina QuímicaFarmacología y FarmaciaHuman Immunodeficiency Virus (HIV) belongs to the Lentivirus genus, Retroviridae family, enveloped by a lipid bilayer within which the capsid protein encases the viral genome, reverse transcriptase, and integrase proteins, key components for viral replication. Viral capsid has been linked to key early and late stages of viral infection, including nuclear entry, promoting reverse transcription and assembly of new viral particles within target TCD4+ lymphocytes. Effective treatments for HIV involve multi drug therapy, which can reduce the patient's viral load to undetectable values, thus avoiding the appearance of Acquired Immunodeficiency Syndrome (AIDS). In this study, a conserved region of the HIV capsid protein was selected and 84 compounds were selected from a massive Artificial Intelligence-based virtual screening as potential HIV capsid assembly disruptors. In vitro screening was performed using recombinant protein and complemental approaches were carried out to identify molecules capable of interfering with capsid multimerization. From this work, 9 compounds were selected as successful to continue through in cell and toxicity assays for further development as possible HIV treatments. In conclusion, this work demonstrates the efficiency of integrating rational computational and experimental methodologies to identify new candidates as potential antiviral molecules.Agencia Nacional de Investigación e InnovaciónUniversidad de la República. Comisión académica de posgradosAgence Nationale de Recherche sur le SIDA - Maladies Infectieuses ÉmergentesAtomwise Inc.Universidad de la República. Comisión Sectorial de Investigación CientíficaElsevier2025-10-28T18:32:42Z2026-05-12T03:30:12Z2025-05-12Artículoinfo:eu-repo/semantics/articleAceptadoinfo:eu-repo/semantics/acceptedVersionhttps://hdl.handle.net/20.500.12381/5273FCE_3_2022_1_172494https://doi.org/10.1016/j.bbrc.2025.151572Biochemical and Biophysical Research Communicationsreponame:REDIinstname:Agencia Nacional de Investigación e Innovacióninstacron:Agencia Nacional de Investigación e Innovaciónenghttps://hdl.handle.net/20.500.12381/5280https://hdl.handle.net/20.500.12381/5284https://hdl.handle.net/20.500.12381/5285https://hdl.handle.net/20.500.12381/5286https://hdl.handle.net/20.500.12381/5305Acceso abiertoinfo:eu-repo/semantics/openAccessReconocimiento-NoComercial-SinObraDerivada 4.0 Internacional. (CC BY-NC-ND)El artículo no se encuentra en una revista de acceso abierto2026-05-12oai:redi.anii.org.uy:20.500.12381/52732026-06-16T05:02:04Z |
| spellingShingle | Integrating different approaches for the identification of new disruptors of HIV-1 capsid multimerization Artía, Zoraima Artificial intelligence Capsid Drug development HIV-1 Screening Ciencias Médicas y de la Salud Medicina Básica Bioquímica y Biología Molecular Medicina Química Farmacología y Farmacia |
| status_str | acceptedVersion |
| title | Integrating different approaches for the identification of new disruptors of HIV-1 capsid multimerization |
| title_full | Integrating different approaches for the identification of new disruptors of HIV-1 capsid multimerization |
| title_fullStr | Integrating different approaches for the identification of new disruptors of HIV-1 capsid multimerization |
| title_full_unstemmed | Integrating different approaches for the identification of new disruptors of HIV-1 capsid multimerization |
| title_short | Integrating different approaches for the identification of new disruptors of HIV-1 capsid multimerization |
| title_sort | Integrating different approaches for the identification of new disruptors of HIV-1 capsid multimerization |
| topic | Artificial intelligence Capsid Drug development HIV-1 Screening Ciencias Médicas y de la Salud Medicina Básica Bioquímica y Biología Molecular Medicina Química Farmacología y Farmacia |
| url | https://hdl.handle.net/20.500.12381/5273 https://doi.org/10.1016/j.bbrc.2025.151572 |