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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Non-Toxic Dimeric Peptides Derived from the Bothropstoxin-I Are Potent SARS-CoV-2 and Papain-like Protease Inhibitors

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Freire, Marjorie C. L. C. [1] ; Noske, Gabriela D. [1] ; Bitencourt, Natalia V. [2] ; Sanches, Paulo R. S. [2] ; Santos-Filho, Norival A. [2] ; Gawriljuk, Victor O. [1] ; de Souza, Eduardo P. [3] ; Nogueira, Victor H. R. [1] ; de Godoy, Mariana O. [1] ; Nakamura, Aline M. [1] ; Fernandes, Rafaela S. [1] ; Godoy, Andre S. [1] ; Juliano, Maria A. [4] ; Peres, Bianca M. [5] ; Barbosa, Cecilia G. [5] ; Moraes, Carolina B. [6] ; Freitas-Junior, Lucio H. G. [5] ; Cilli, Eduardo M. [2] ; Guido, Rafael V. C. [1] ; Oliva, Glaucius [1]
Total Authors: 20
Affiliation:
[1] Univ Sao Paulo, Sao Carlos Inst Phys, Ave Joao Dagnone 1100, BR-13563120 Sao Carlos, SP - Brazil
[2] Sao Paulo State Univ Unesp, Inst Chem, Dept Biochem & Organ Chem, BR-14800060 Araraquara, SP - Brazil
[3] Univ Fed Sao Carlos, Dept Genet & Evolut, Rodovia Washington Luis Km 235, BR-13565905 Sao Carlos, SP - Brazil
[4] Univ Fed Sao Paulo, Sao Paulo Sch Med, Rua Tres Maio 100, BR-04044020 Sao Paulo, SP - Brazil
[5] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Av Prof Lineu Prestes 1374, BR-05508900 Sao Paulo, SP - Brazil
[6] Univ Fed Sao Paulo, Dept Pharmaceut Sci, Rua Sao Nicolau 210, BR-09913030 Diadema, SP - Brazil
Total Affiliations: 6
Document type: Journal article
Source: Molecules; v. 26, n. 16 AUG 2021.
Web of Science Citations: 0
Abstract

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-Cys(11), Lys(12),Lys(13)-(pBthTX-I)(2)K ((pBthTX-I)(2)K)) and derivatives against SARS-CoV-2 are reported. The lead peptide (pBthTX-I)(2)K and derivatives showed attractive inhibitory activities against SARS-CoV-2 (EC50 = 28-65 mu M) and mostly low cytotoxic effect (CC50 > 100 mu M). To shed light on the mechanism of action underlying the peptides' antiviral activity, the Main Protease (M-pro) and Papain-Like protease (PLpro) inhibitory activities of the peptides were assessed. The synthetic peptides showed PLpro inhibition potencies (IC(50)s = 1.0-3.5 mu M) and binding affinities (K-d = 0.9-7 mu M) at the low micromolar range but poor inhibitory activity against M-pro (IC50 > 10 mu M). 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. (AU)

FAPESP's process: 18/17095-8 - Structural characterization of the Chikungunya Virus NSP4 RNA-dependent RNA polymerase and search for antiviral agents
Grantee:Marjorie Caroline Liberato Cavalcanti Freire
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 20/04602-9 - Development of antivirals for the treatment of COVID-19
Grantee:Glaucius Oliva
Support type: Regular Research Grants
FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
Grantee:Glaucius Oliva
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 20/05761-3 - Study of the action of synthetic peptides as antivirals against SARS-CoV-2 (COVID-19) and combined evaluation with commercial anti-inflammatories
Grantee:Eduardo Maffud Cilli
Support type: Regular Research Grants
FAPESP's process: 20/12519-4 - Study of the action of synthetic peptides as antivirals against SARS-CoV-2 (COVID-19) and combined evaluation with commercial anti-inflammatories
Grantee:Paulo Ricardo da Silva Sanches
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 18/25600-4 - Discovery and development of antiviral candidates against Yellow Fever virus based on the structure of the NS2B-NS3 protease complex
Grantee:Gabriela Dias Noske
Support type: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 16/19712-9 - Structural characterization of Zika virus proteins and search for antiviral agents
Grantee:Andre Schutzer de Godoy
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 16/13884-2 - Multi-User Equipment approved in grant 2013/07600-3: MicroScale Thermophoresis (MST)
Grantee:Glaucius Oliva
Support type: Multi-user Equipment Program
FAPESP's process: 18/13588-0 - Multi - user equipment approved in grant 2012/50191-4: mass spectrometer impact II - Bruker
Grantee:Maria Aparecida Juliano
Support type: Multi-user Equipment Program