Non-toxic dimeric peptides derived from the bothropstoxin-I are potent SARS-CoV-2 and papain-like protease inhibitors
Nenhuma Miniatura disponível
Data
2021-08-02
Autores
Freire, Marjorie C. L. C.
Noske, Gabriela D.
Bitencourt, Natália V. [UNESP]
Sanches, Paulo R. S. [UNESP]
Santos-Filho, Norival A. [UNESP]
Gawriljuk, Victor O.
de Souza, Eduardo P.
Nogueira, Victor H. R.
de Godoy, Mariana O.
Nakamura, Aline M.
Título da Revista
ISSN da Revista
Título de Volume
Editor
Resumo
The COVID-19 outbreak has rapidly spread on a global scale, affecting the economy and public health systems throughout the world. In recent years, peptide-based therapeutics have been widely studied and developed to treat infectious diseases, including viral infections. Herein, the antiviral effects of the lysine linked dimer des-Cys11, Lys12,Lys13-(pBthTX-I)2K ((pBthTX-I)2K)) and derivatives against SARS-CoV-2 are reported. The lead peptide (pBthTX-I)2K and derivatives showed attractive inhibitory activities against SARS-CoV-2 (EC50 = 28–65 µM) and mostly low cytotoxic effect (CC50 > 100 µM). To shed light on the mechanism of action underlying the peptides’ antiviral activity, the Main Protease (Mpro) and Papain-Like protease (PLpro) inhibitory activities of the peptides were assessed. The synthetic peptides showed PLpro inhibition potencies (IC50s = 1.0–3.5 µM) and binding affinities (Kd = 0.9–7 µM) at the low micromolar range but poor inhibitory activity against Mpro (IC50 > 10 µM). The modeled binding mode of a representative peptide of the series indicated that the compound blocked the entry of the PLpro substrate toward the protease catalytic cleft. Our findings indicated that non-toxic dimeric peptides derived from the Bothropstoxin-I have attractive cellular and enzymatic inhibitory activities, thereby suggesting that they are promising prototypes for the discovery and development of new drugs against SARS-CoV-2 infection.
Descrição
Palavras-chave
COVID-19, Inhibitors, Papain-like protease, Peptides, SARS-CoV-2
Como citar
Molecules, v. 26, n. 16, 2021.