Author(s):
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. ; Fernandes, Rafaela S. ; Godoy, Andre S. ; Juliano, Maria A. ; Peres, Bianca M. ; Barbosa, Cecília G. ; Moraes, Carolina B. ; Freitas-Junior, Lucio H. G. ; Cilli, Eduardo M. [UNESP] ; Guido, Rafael V. C. ; Oliva, Glaucius
Date: 2022
Persistent ID: http://hdl.handle.net/11449/229351
Origin: Oasisbr
Subject(s): COVID-19; Inhibitors; Papain-like protease; Peptides; SARS-CoV-2
Description
Made available in DSpace on 2022-04-29T08:32:05Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-08-02
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
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.
São Carlos Institute of Physics University of Sao Paulo, Avenida João Dagnone, 1100
Department of Biochemistry and Organic Chemistry Institute of Chemistry São Paulo State University (UNESP)
Department of Genetics and Evolution Federal University of São Carlos, Rodovia Washington Luís km 235
The Sao Paulo School of Medicine Federal University of São Paulo, Rua Três de Maio, 100
Department of Microbiology Institute of Biomedical Sciences University of Sao Paulo, Av. Prof. Lineu Prestes, 1374
Department of Pharmaceutical Sciences Federal University of São Paulo, Rua São Nicolau, 210
Department of Biochemistry and Organic Chemistry Institute of Chemistry São Paulo State University (UNESP)
CAPES: 001
FAPESP: 2013/07600-3
FAPESP: 2018/13588-0
FAPESP: 2020/04602-9
FAPESP: 2020/05761-3
FAPESP: 2020/12519-4
CNPq: 301975/2018-3
