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1.
Pharmacol Res Perspect ; 9(1): e00705, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33421347

RESUMO

Drug-drug interaction (DDI) is a common clinical problem that has occurred as a result of the concomitant use of multiple drugs. DDI may occur in patients under treatment with medications used for coronavirus disease 2019 (COVID-19; i.e., chloroquine, lopinavir/ritonavir, ribavirin, tocilizumab, and remdesivir) and increase the risk of serious adverse reactions such as QT-prolongation, retinopathy, increased risk of infection, and hepatotoxicity. This review focuses on summarizing DDIs for candidate medications used for COVID-19 in order to minimize the adverse reactions.


Assuntos
Antivirais/uso terapêutico , /tratamento farmacológico , Animais , Anticorpos Monoclonais Humanizados/uso terapêutico , Cloroquina/uso terapêutico , Interações Medicamentosas , Humanos , Lopinavir/uso terapêutico , Ribavirina/uso terapêutico , Ritonavir/uso terapêutico
2.
Iran J Pharm Res ; 18(2): 759-771, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31531059

RESUMO

Tumor necrosis factor alpha (TNF-α) is an inflammatory cytokine which plays crucial roles in pathogenesis of inflammatory diseases. The current study aimed to investigate the binding abilities of I44 and I49 domain antibodies to TNF-α. The dAbs were expressed in bacterial expression system and purified by affinity chromatography using Ni-sepharose column. The expression and purity of the proteins were evaluated using western blotting and SDS-PAGE techniques, respectively. ELISA experiment showed that I44 and I49 dAbs bind to TNF-α with the binding constants (Kd) of 5.18 ± 1.41 and 2.42 ± 0.55 µM, respectively. The inhibitory effect of dAbs on TNF-α biological effect was determined in MTT assay in which I44 and I49 prevented TNF-α cell cytotoxicity with IC50 values of 6.61 and 3.64 µM, respectively. The identified anti-TNF-α dAbs could bind to and inhibit TNF-α activity. The dAbs activities can be attributed to their ability to establish hydrogen bonds as well as hydrophobic contacts with TNF-α. The results of the current study can pave the way for further structural studies in order to introduce new more potent anti-TNF-α antibodies.

3.
Prep Biochem Biotechnol ; 49(1): 38-47, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30735094

RESUMO

Single-chain fragment variable (scFv) antibodies are antibody fragments consist of variable domains of full antibodies known to retain antigen binding properties while having much lower molecular weights granting some beneficial properties to them. In our previous study, three phage particles each displaying an individual scFv antibody (i.e. J43, J44, and J48) were identified as tumor necrosis factor alpha (TNF-α) binders. The current study aimed to produce previously identified anti-TNF-α scFv antibodies and to investigate their abilities to bind and inhibit TNF-α biological effect. The estimated free energy of folding determined using spectrofluorimetry method for the prepared scFv proteins was in the range of 6.35-12.45 kJ mol-1 indicating their proper folding in the solution. In ELISA experiment, the produced scFvs showed an appropriate affinity towards TNF-α with Kd values in the range of 0.5-2.18 µM. They also inhibited the TNF-α-induced cytotoxicity on L929 cells with sub-micromolar IC50 values (0.12 and 0.73 µM for J44 and J48, respectively). Molecular docking studies showed that J44 could mimic adalimumab interactions with TNF-α, confirming its relatively high TNF-α inhibitory effect compared to J43 and J48. It seems that the findings in the current study can be useful for designing more potent anti-TNF-α antibodies.


Assuntos
Simulação por Computador , Anticorpos de Cadeia Única/imunologia , Fator de Necrose Tumoral alfa/imunologia , Animais , Western Blotting , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Eletroforese em Gel de Poliacrilamida , Ensaio de Imunoadsorção Enzimática , Concentração Inibidora 50 , Camundongos , Simulação de Acoplamento Molecular , Mutagênese Sítio-Dirigida , Reação em Cadeia da Polimerase , Espectrometria de Fluorescência , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/farmacologia
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