RESUMO
Global Human Immunodeficiency Virus (HIV) statistics by the World Health Organization (WHO) for the year 2017 was estimated to be 36.9 (31.1-43.9) million. Antiviral drug resistance poses a serious threat to public health and requires immediate action. Retroviral Integrase (IN), a component enzyme in the retroviral pre-integration complex (PIC) enables a retrovirus to incorporate its genetic material into the host DNA. Development of resistance by the current integrases invites immediate attention of the drug discovery community for the development of new second-generation Integrase Strand Transfer Inhibitors (INSTIs). It will exhibit greater efficacy against Elvitegravir (EVG) and Raltegravir (RAL) resistant strains of HIV. This review focuses on the mechanism, importance of integrase structure, function and current research on small molecule inhibitors of integrase to overcome drug resistance. The molecular mechanism of retroviral integrase inhibition and the evolution of resistance are also explored.
Assuntos
Desenvolvimento de Medicamentos/métodos , Farmacorresistência Viral/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/farmacologia , HIV/efeitos dos fármacos , Integrases/metabolismo , Ensaios Clínicos como Assunto , HIV/enzimologia , Infecções por HIV/virologia , Inibidores de Integrase de HIV/química , Humanos , Modelos Moleculares , Estrutura Molecular , Ligação ProteicaRESUMO
Galectin 1(Gal-1), a ß-galactoside binding mammalian lectin of 14KDa, is implicated in many signalling pathways, immune responses associated with cancer progression and immune disorders. Inhibition of human Gal-1 has been regarded as one of the potential therapeutic approaches for the treatment of cancer, as it plays a major role in tumour development and metastasis by modulating various biological functions viz. apoptosis, angiogenesis, migration, cell immune escape. Gal-1 is considered as a biomarker in diagnosis, prognosis and treatment condition. The overexpression of Gal-1 is well established and seen in many types of cancer progression like osteosarcoma, breast, lung, prostate, melanoma, etc. Gal-1 greatly accelerates the binding kinetics of HIV-1 to susceptible cells, leading to faster viral entry and a more robust viral replication by specific binding of CD4 cells. Hence, the Gal-1 is considered a promising molecular target for the development of new therapeutic drugs for cancer and HIV. The present review laid emphasis on structural insights and functional role of Gal-1 in the disease, current Gal-1 inhibitors and future prospects in the design of specific Gal-1 inhibitors.
