Unveiling ancestral threads: Exploring CCR5 ∆32 mutation frequencies in Colombian populations for HIV/AIDS therapeutics DOI Creative Commons

Alejandro Barrios-Navas,

Thanh Long Nguyen,

Juan Esteban Gallo

и другие.

Infection Genetics and Evolution, Год журнала: 2024, Номер 125, С. 105680 - 105680

Опубликована: Окт. 5, 2024

AIDS remains a significant global health challenge since its emergence in 1981, with millions of deaths and new cases every year. The CCR5 ∆32 genetic deletion confers immunity to HIV infection by altering cell membrane protein crucial for viral entry. Stem transplants from homozygous carriers this mutation HIV-infected individuals have resulted load reduction disease remission, suggesting potential therapeutic avenue. This study aims investigate the relationship between ancestry frequency Colombian populations, exploring feasibility targeted donor searches based on composition. Utilizing genomic data CÓDIGO-Colombia consortium, comprising 532 individuals, assessed presence examined if population was Hardy-Weinberg equilibrium. Individuals were stratified into clusters African, American, European percentages, logistic regression analysis performed evaluate association frequency. Additionally, databases utilized visualize worldwide distribution mutation. findings revealed positive frequency, underscoring relevance selection. African American showed negative but non-significant associations which may be attributed study's limitations. These results emphasize importance considering selection strategies, reveal scarcity donors Colombia, underscore need consider other populations mainly stem transplant becomes routine treatment HIV/AIDS Colombia.

Язык: Английский

Development of Anti-HIV Therapeutics: From Conventional Drug Discovery to Cutting-Edge Technology DOI Creative Commons
Yaping Sun, Lingyun Wang

Pharmaceuticals, Год журнала: 2024, Номер 17(7), С. 887 - 887

Опубликована: Июль 4, 2024

The efforts to discover HIV therapeutics have continued since the first human immunodeficiency virus (HIV) infected patient was confirmed in 1980s. Ten years later, drug, zidovudine (AZT), targeting reverse transcriptase, developed. Meanwhile, scientists were enlightened new drugs that target different genes, like integrase, protease, and host receptors. Combination antiretroviral therapy (cART) is most feasible medical intervention suppress people with (PWH) control epidemic. ART treatment has made a chronic infection rather than fatal disease, but does not eliminate latent reservoirs of HIV-1 from cells; strict life-long adherence required for be effective patients. In this review, we discussed scientific history conventional drug discovery need develop more solve drug-resistant issues release side effects. Then, summarized novel research technologies, gene editing, applied their contributions eliminating as complementary therapy.

Язык: Английский

Процитировано

5
Structure-based Design of Novel 2,4,5-Trisubstituted Pyrimidine Derivatives as Potent HIV-1 NNRTIs by Exploiting the Tolerant Regions in NNTRIs Binding Pocket DOI

Zhenzhen Zhou,

Minghui Xie,

Zongji Zhuo

и другие.

European Journal of Medicinal Chemistry, Год журнала: 2025, Номер 289, С. 117464 - 117464

Опубликована: Фев. 27, 2025

Язык: Английский

Процитировано

0
Deep Thought on the HIV Cured Cases: Where Have We Been and What Lies Ahead? DOI Creative Commons
Qing Xiao, Sanxiu He, Chaoyu Wang

и другие.

Biomolecules, Год журнала: 2025, Номер 15(3), С. 378 - 378

Опубликована: Март 5, 2025

Antiretroviral therapy (ART) can effectively suppress the replication of human immunodeficiency virus (HIV), but it cannot completely eradicate virus. The persistent existence HIV reservoir is a major obstacle in quest for cure. To date, there have been total seven cured cases worldwide. These patients all cleared while undergoing allogeneic stem cell transplantation (allo-HSCT) hematological malignancies. However, these cases, specific mechanism by which allo-HSCT leads to eradication remains unclear, so necessary conduct an in-depth analysis. Due difficulty obtaining donors and risks associated with transplantation, this treatment method not applicable patients. There still need explore new strategies. In recent years, emerging therapies such as neutralizing antibody immunotherapy, chimeric antigen receptor T (CAR-T) therapy, gene editing, antiviral targeting attracted wide attention due their ability inhibit replication. This article first elaborates on nature reservoir, then deeply explores modalities potential success factors finally discusses current novel methods, hoping provide comprehensive feasible strategies achieving cure HIV.

Язык: Английский

Процитировано

0
Addition of a short HIV-1 fusion-inhibitory peptide to PRO 140 antibody dramatically increases its antiviral breadth and potency DOI Creative Commons

Hongxia Yan,

Gao Yue,

Yuanmei Zhu

и другие.

Journal of Virology, Год журнала: 2025, Номер unknown

Опубликована: Март 25, 2025

ABSTRACT PRO 140, a humanized anti-HIV monoclonal antibody targeting the cell coreceptor CCR5, is currently under clinical trials, but it only affects CCR5-tropic viruses. In this study, we have engineered two tandem fusion proteins (2P23-PRO140SC and 2P23-PRO140-Fc) with bifunctional activity by adding short fusion-inhibitory peptide 2P23 to single-chain fragment variable (scFv) of 140 (PRO140SC) or without Fc domain human IgG4. We first demonstrated that 2P23-PRO140SC 2P23-PRO140-Fc could efficiently bind membranes through CCR5 anchoring, which did not affect expression level on surface. then verified addition PRO140SC enabled very potent against CXCR4-tropic HIV-1 isolates. As expected, bispecific exhibited highly activities in inhibiting divergent subtypes viral mutants were resistant inhibitors T20, they displayed relatively low vitro cytotoxicity. Furthermore, both had robust vivo rats, much better than 2P23-PRO140SC. conclusion, our studies provided overcome drawbacks offered novel tools for studying mechanisms infection. IMPORTANCE Given evolves high variability drug resistance, development antivirals important. CCR5-directed inhibits The designed minimum enable dramatically increased viruses, thus offering antiviral agents functionality can antibody.

Язык: Английский

Процитировано

0
Unveiling ancestral threads: Exploring CCR5 ∆32 mutation frequencies in Colombian populations for HIV/AIDS therapeutics DOI Creative Commons

Alejandro Barrios-Navas,

Thanh Long Nguyen,

Juan Esteban Gallo

и другие.

Infection Genetics and Evolution, Год журнала: 2024, Номер 125, С. 105680 - 105680

Опубликована: Окт. 5, 2024

AIDS remains a significant global health challenge since its emergence in 1981, with millions of deaths and new cases every year. The CCR5 ∆32 genetic deletion confers immunity to HIV infection by altering cell membrane protein crucial for viral entry. Stem transplants from homozygous carriers this mutation HIV-infected individuals have resulted load reduction disease remission, suggesting potential therapeutic avenue. This study aims investigate the relationship between ancestry frequency Colombian populations, exploring feasibility targeted donor searches based on composition. Utilizing genomic data CÓDIGO-Colombia consortium, comprising 532 individuals, assessed presence examined if population was Hardy-Weinberg equilibrium. Individuals were stratified into clusters African, American, European percentages, logistic regression analysis performed evaluate association frequency. Additionally, databases utilized visualize worldwide distribution mutation. findings revealed positive frequency, underscoring relevance selection. African American showed negative but non-significant associations which may be attributed study's limitations. These results emphasize importance considering selection strategies, reveal scarcity donors Colombia, underscore need consider other populations mainly stem transplant becomes routine treatment HIV/AIDS Colombia.

Язык: Английский

Процитировано

1