Study of the action of synthetic peptides as antivirals against SARS-CoV-2 (COVID-19) and combined evaluation with commercial anti-inflammatories

• Grant number: 20/05761-3
• Support Opportunities: Regular Research Grants
• Duration: July 01, 2020 - June 30, 2022
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Eduardo Maffud Cilli
• Grantee: Eduardo Maffud Cilli
• Host Institution: Instituto de Química (IQ). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated researchers: Cintia Bittar Oliva ; Marilia de Freitas Calmon ; Norival Alves Santos Filho ; Paula Rahal ; Paulo Ricardo da Silva Sanches
• Associated research grant: 17/24839-0 - Nanoelectronics and nanoscale electrochemistry: fundaments and applications, AP.TEM
• Associated scholarship(s): 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, BP.PD

Abstract

Human pandemics, emerging and re-emerging viruses and the mutation of viral strains have been highlighting the importance for antiviral research. Pandemics, such as the actual caused by SARS-CoV-2, directly affect the world, mainly the public health, economy, tourism, etc. Also, due his high and fast spreading, this disease are saturating hospitals worldwide and the number of deaths are increasing constantly. Due the actual severe global health problem caused by SARS-CoV-2 and moved for the urgency for the development of treatments for this disease and future pandemics, the search for new compounds to treat infections by SARS-Cov-2 represents an important research area. Therefore, the objective of this project is identify and evaluate potential peptides able to inhibit virus SARS-CoV-2 infection progression in different steps of virus replication in vitro such as virucidal, receptor binding and cytoplasmic replication. Peptides and bioconjugates have been showing high antiviral potential in different steps of virus lifecycle. According to antiviral activity, compounds will be classified within groups (Virucidal, Inhibitor of receptor binding and inhibitor of cytoplasmic replication) and the action mechanism will be elucidate. Additionally, selected peptides will be evaluated together with anti-inflammatories (Ibuprofen and Ketoprofen) to evaluate the combination of antiviral and anti-inflammatory therapies. (AU)

Scientific publications

(10)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MENDONCA-GOMES, JULIANA MOREIRA; CHARLIE-SILVA, IVES; GUIMARAES, ABRAAO TIAGO BATISTA; ESTRELA, FERNANDA NEVES; CALMON, MARILIA FREITAS; MICELI, RAFAEL NAVA; SANCHES, PAULO R. S.; BITTAR, CINTIA; RAHAL, PAULA; CILLI, EDUARDO M.; et al. Shedding light on toxicity of SARS-CoV-2 peptides in aquatic biota: A study involving neotropical mosquito larvae (Diptera: Culicidae). Environmental Pollution, v. 289, NOV 15 2021. (19/19939-1, 20/05761-3)

VENTURA FERNANDES, BIANCA H.; FEITOSA, NATALIA MARTINS; BARBOSA, ANA PAULA; BOMFIM, CAMILA GASQUE; GARNIQUE, ANALI M. B.; ROSA, IVANA F.; RODRIGUES, MAIRA S.; DORETTO, LUCAS B.; COSTA, DANIEL F.; CAMARGO-DOS-SANTOS, BRUNO; et al. oxicity of spike fragments SARS-CoV-2 S protein for zebrafish: A tool to study its hazardous for human health. Science of The Total Environment, v. 813, MAR 20 2022. (19/00195-2, 18/07098-0, 20/05761-3, 17/17303-7, 20/04680-0, 14/04294-1, 19/21739-0, 19/19939-1, 19/18356-2, 19/14285-3, 19/12234-2)

FREIRE, MARJORIE C. L. C.; NOSKE, GABRIELA D.; BITENCOURT, NATALIA V.; SANCHES, PAULO R. S.; SANTOS-FILHO, NORIVAL A.; GAWRILJUK, VICTOR O.; DE SOUZA, EDUARDO P.; NOGUEIRA, VICTOR H. R.; DE GODOY, MARIANA O.; NAKAMURA, ALINE M.; et al. Non-Toxic Dimeric Peptides Derived from the Bothropstoxin-I Are Potent SARS-CoV-2 and Papain-like Protease Inhibitors. Molecules, v. 26, n. 16, AUG 2021. (18/17095-8, 20/04602-9, 13/07600-3, 20/05761-3, 20/12519-4, 18/25600-4, 16/19712-9, 16/13884-2, 18/13588-0)

SANCHES, PAULO RICARDO DA SILVA; SANCHEZ-VELAZQUEZ, RICARDO; BATISTA, MARIANA NOGUEIRA; CARNEIRO, BRUNO MOREIRA; BITTAR, CINTIA; DE LORENZO, GIUDITTA; RAHAL, PAULA; PATEL, ARVIND H.; CILLI, EDUARDO MAFFUD. Antiviral Evaluation of New Synthetic Bioconjugates Based on GA-Hecate: A New Class of Antivirals Targeting Different Steps of Zika Virus Replication. Molecules, v. 28, n. 13, p. 20-pg., 2023-07-01. (13/07600-3, 22/05411-8, 15/23244-8, 20/05761-3, 20/12519-4, 19/08342-4)

ROSA, IVANA F.; PECANHA, ANA P. B.; CARVALHO, TABATA R. B.; ALEXANDRE, LEONARDO S.; FERREIRA, VINICIUS G.; DORETTO, LUCAS B.; SOUZA, BEATRIZ M.; NAKAJIMA, RAFAEL T.; DA SILVA, PATRICK; BARBOSA, ANA P.; et al. Photobiomodulation Reduces the Cytokine Storm Syndrome Associated with COVID-19 in the Zebrafish Model. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 24, n. 7, p. 22-pg., 2023-04-01. (20/05761-3, 19/21739-0, 14/04294-1, 19/19939-1, 20/15237-0, 18/07098-0, 21/06742-5)

SANCHES, PAULO R. S.; CHARLIE-SILVA, IVES; BRAZ, HELYSON L. B.; BITTAR, CINTIA; CALMON, MARILIA FREITAS; RAHAL, PAULA; CILLI, EDUARDO M.. Recent advances in SARS-CoV-2 Spike protein and RBD mutations comparison between new variants Alpha (B.1.1.7, United Kingdom), Beta (B.1.351, South Africa), Gamma (P.1, Brazil) and Delta (B.1.617.2, India). JOURNAL OF VIRUS ERADICATION, v. 7, n. 3, SEP 2021. (20/12519-4, 20/05761-3)

MALAFAIA, GUILHERME; AHMED, MOHAMED AHMED IBRAHIM; DE SOUZA, SINDOVAL SILVA; ESTRELA REZENDE, FERNANDA NEVES; FREITAS, ITALO NASCIMENTO; DA LUZ, THIARLEN MARINHO; DA SILVA, ABNER MARCELINO; CHARLIE-SILVA, IVES; BEZERRA BRAZ, HELYSON LUCAS; BEZERRA JORGE, ROBERTA JEANE; et al. Toxicological impact of SARS-CoV-2 on the health of the neotropical fish, Poecilia reticulata. AQUATIC TOXICOLOGY, v. 245, p. 12-pg., 2022-04-01. (19/19939-1, 20/05761-3)

CHARLIE-SILVA, IVES; ARAUJO, AMANDA P. C.; GUIMARAES, ABRAAO T. B.; VERAS, FLAVIO P.; BRAZ, HELYSON L. B.; PONTES, LETICIA G. DE; JORGE, ROBERTA J. B.; BELO, MARCO A. A.; FERNANDES, BIANCA H. V.; NOBREGA, RAFAEL H.; et al. Toxicological insights of Spike fragments SARS-CoV-2 by exposure environment: A threat to aquatic health?. JOURNAL OF HAZARDOUS MATERIALS, v. 419, OCT 5 2021. (20/05761-3)

NOGUEIRA, RUBEN SIEDLARCZYK; SALU, BRUNO RAMOS; NARDELLI, VINICIUS GOULART; BONTURI, CAMILA RAMALHO; PEREIRA, MARINA RODRIGUES; MAFFEI, FRANCISCO HUMBERTO DE ABREU; CILLI, EDUARDO MAFFUD; OLIVA, MARIA LUIZA VILELA. A snake venom-analog peptide that inhibits SARS-CoV-2 and papain-like protease displays antithrombotic activity in mice arterial thrombosis model, without interfering with bleeding time. THROMBOSIS JOURNAL, v. 21, n. 1, p. 10-pg., 2023-01-02. (17/06630-7, 20/05761-3, 19/22243-9, 20/01512-9)

CASTRO, ANA C. H.; BEZERRA, ITALO R. S.; PASCON, ALINE M.; DA SILVA, GABRIELA H.; PHILOT, ERIC A.; DE OLIVEIRA, VIVIAN L.; MANCINI, RODRIGO S. N.; SCHLEDER, GABRIEL R.; CASTRO, CARLOS E.; DE CARVALHO, LUCIANI R. S.; et al. Modular Label-Free Electrochemical Biosensor Loading Nature-Inspired Peptide toward the Widespread Use of COVID-19 Antibody Tests. ACS NANO, v. 16, n. 9, p. 15-pg., 2022-09-27. (17/02317-2, 19/19939-1, 14/50867-3, 20/05761-3)