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
• Start date: July 01, 2020
• End date: 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
• City of the host institution: Araraquara
• 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

(13)

(The scientific publications listed on this page originate from the Web of Science or SciELO databases. Their authors have cited FAPESP grant or fellowship project numbers awarded to Principal Investigators or Fellowship Recipients, whether or not they are among the authors. This information is collected automatically and retrieved directly from those bibliometric databases.)

LIMA, MARIA LETICIA DUARTE; SANCHES, PAULO RICARDO DA SILVA; GERALDINI, DAYLA BOTT; AYUSSO, GABRIELA MIRANDA; DA CONCEICAO, PAMELA JOYCE PREVIDELLI; CARVALHO, TAMARA; GONZALEZ, JORGE ENRIQUE HERNANDEZ; GISMENE, CAROLINA; BITTAR, CINTIA; ARNI, RAGHUVIR KRISHNASWAMY; et al. A new synthetic peptide GA-KKALKKLKKALKKAL-CONH2 exhibits antiviral activity against ZIKV in multiple stages of the replicative cycle. VIROLOGY, v. 611, p. 12-pg., 2025-07-29. (22/03901-8, 23/02956-6, 23/04491-0, 24/00876-8, 19/07784-3, 24/13327-2, 20/05761-3, 22/05411-8, 20/08615-8)

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)

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)

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)

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)

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)

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)

DA SILVA SANCHES, PAULO RICARDO; CILLI, EDUARDO MAFFUD. The Use of Virus-like Particles as Immunogens to Treat Infectious Diseases. CURRENT TOPICS IN MEDICINAL CHEMISTRY, v. N/A, p. 11-pg., 2025-07-17. (23/02956-6, 20/05761-3, 22/05411-8)

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)

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)

SANCHES, PAULO RICARDO DA S.; FARIA, JOAO CALDANA ELIAS DE CAMPOS; BITTAR, CINTIA; OLIVIERI, HUGO ALEXANDRE SIQUEIRA GUBEROVICH; MESQUITA, NATHALYA CRISTINA DE MORAES ROSO; NOSKE, GABRIELA DIAS; DE GODOY, ANDRE SCHUTZER; OLIVA, GLAUCIUS; RAHAL, PAULA; CILLI, EDUARDO MAFFUD. The GA-Hecate Peptide inhibits the ZIKV Replicative Cycle in Different Steps and can Inhibit the Flavivirus NS2B-NS3 Protease after Cell Infection. PROTEIN AND PEPTIDE LETTERS, v. 31, n. 7, p. 12-pg., 2024-07-19. (22/11644-5, 20/05761-3, 22/05411-8, 19/08342-4, 13/07600-3, 20/12519-4, 15/23244-8)

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)

Filed patent(s) as a result of this research project