Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 3 de 3
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
ChemMedChem ; 18(16): e202300216, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37248169

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is an unprecedented global health emergency causing more than 6.6 million fatalities by 31 December 2022. So far, only three antiviral drugs have been granted emergency use authorisation or approved by the FDA. The SARS-CoV-2 papain-like protease (PLpro ) is deemed an attractive drug target as it plays an essential role in viral polyprotein processing and pathogenesis although no inhibitors have yet been approved. This patent review discusses coronavirus PLpro inhibitors reported in patents published between 1 January 2003 to 2 March 2023, giving an overview on the inhibitors that have generated commercial interest, especially amongst drug companies.


Assuntos
COVID-19 , Papaína , Humanos , Peptídeo Hidrolases , Proteases Semelhantes à Papaína de Coronavírus , SARS-CoV-2 , Antivirais/farmacologia , Inibidores de Proteases/farmacologia
2.
Antiviral Res ; 118: 68-74, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25823617

RESUMO

The dengue virus is a mosquito-borne pathogen responsible for an estimated 50-100 million human dengue infections annually. There are currently no approved drugs against this disease, resulting in a major unmet clinical need. The dengue viral NS2B-NS3 protease has been identified as a plausible drug target due to its involvement in viral replication in mammalian host cells. In the past decade, at least 20 dengue NS2B-NS3 protease inhibitors have been reported in the literature with a range of inhibitory activities in protease assays. However, such assays do not shed light on an inhibitor's ability to penetrate human cell membranes where the viral protease resides. In this study, we investigated the antiviral activities of 15 small-molecule and peptide-based NS2B-NS3 inhibitors on dengue serotype 2-infected HuH-7 human hepatocarcinoma cells. Experimental results revealed anthraquinone ARDP0006 (compound 5) to be the most potent inhibitor which reduced dengue viral titer by more than 1 log PFU/mL at 1 µM in our cell-based assays involving HuH-7 and K562 cell lines, suggesting that its scaffold could serve as a lead for further medicinal chemistry studies. Compound 5 was also found to be non-cytotoxic at 1 µM over 3 days incubation on HuH-7 cells using the Alamar Blue cellular toxicity assay.


Assuntos
Antraquinonas/farmacologia , Antivirais/farmacologia , Vírus da Dengue/enzimologia , Inibidores de Proteases/farmacologia , Carga Viral , Proteínas não Estruturais Virais/antagonistas & inibidores , Antraquinonas/toxicidade , Antivirais/toxicidade , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Vírus da Dengue/efeitos dos fármacos , Vírus da Dengue/fisiologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/virologia , Humanos , Testes de Sensibilidade Microbiana , Inibidores de Proteases/toxicidade , RNA Helicases/antagonistas & inibidores , Serina Endopeptidases
3.
Antiviral Res ; 92(1): 96-101, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21763725

RESUMO

A series of tripeptide aldehyde inhibitors were synthesized and their inhibitory effect against dengue virus type 2 (DENV2) and West Nile virus (WNV) NS3 protease was evaluated side by side with the aim to discover potent flaviviral protease inhibitors and to examine differences in specificity of the two proteases. The synthesized inhibitors feature a varied N-terminal cap group and side chain modifications of a P2-lysine residue. In general a much stronger inhibitory effect of the tripeptide inhibitors was observed toward WNV protease. The inhibitory concentrations against DENV2 protease were in the micromolar range while they were submicromolar against WNV. The data suggest that a P2-arginine shifts the specificity toward DENV2 protease while WNV protease favors a lysine in the P2 position. Peptides with an extended P2-lysine failed to inhibit DENV2 protease suggesting a size-constrained S2 pocket. Our results generally encourage the investigation of di- and tripeptide aldehydes as inhibitors of DENV and WNV protease.


Assuntos
Vírus da Dengue/efeitos dos fármacos , Oligopeptídeos/farmacologia , Inibidores de Proteases/farmacologia , Proteínas Virais/antagonistas & inibidores , Vírus do Nilo Ocidental/efeitos dos fármacos , Sítios de Ligação , Vírus da Dengue/química , Vírus da Dengue/enzimologia , Vírus da Dengue/genética , Modelos Moleculares , Estrutura Molecular , Oligopeptídeos/síntese química , Oligopeptídeos/química , Peptídeo Hidrolases/química , Peptídeo Hidrolases/metabolismo , Inibidores de Proteases/síntese química , Inibidores de Proteases/química , Ligação Proteica , Relação Estrutura-Atividade , Proteínas Virais/química , Proteínas Virais/metabolismo , Vírus do Nilo Ocidental/química , Vírus do Nilo Ocidental/enzimologia , Vírus do Nilo Ocidental/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...