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Entree

Drug discovery contra doenças infecciosas humanos

Processo: 15/26722-8
Modalidade de apoio:Auxílio à Pesquisa - Temático
Vigência: 01 de março de 2017 - 31 de outubro de 2024
Área do conhecimento:Ciências Biológicas - Farmacologia - Farmacologia Bioquímica e Molecular
Pesquisador responsável:Carsten Wrenger
Beneficiário:Carsten Wrenger
Instituição Sede: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brasil
Pesquisadores principais:
Alessandro Silva Nascimento
Pesquisadores associados:Cláudio Romero Farias Marinho ; Helio Alexandre Stefani ; Igor Polikarpov
Auxílios(s) vinculado(s):19/00899-0 - Dissecação estrutural de nanopartículas assistidas: entrega de medicamentos nas doenças infecciosas humanas, AP.R SPRINT
17/07253-2 - EMU 2015/26722-8 DLS ZetaSizer microV, AP.EMU
17/03042-7 - EMU 2015/26722-8 CLARIOstar microplate reader, AP.EMU
17/03047-9 - EMU 2015/26722-8 Avanti J-30 I Biosafe® centrifuge including rotor, AP.EMU
17/04782-4 - EMU 2015/26722-8 AKTA pure gel filtration system, AP.EMU
Bolsa(s) vinculada(s):22/01812-8 - Interferência com a montagem de vírions SARS-CoV-2 direcionados à proteína E por rational drug design, BP.DR
21/00124-8 - Análise da SUMOlação das proteínas do Plasmodium falciparum, durante o estresse oxidativo, em eritrócitos com atividade glicose-6-fosfato desidrogenase parcialmente deficiente, BP.MS
20/12277-0 - Drug discovery contra doenças infecciosas humanas, BP.PD
+ mais bolsas vinculadas 19/20219-3 - Estudos estruturais das enzimas envolvidas na síntese de vitaminas B1 e B6 em Plasmodium, BP.PD
18/21213-6 - Caracterização estrutural das enzimas da via de síntese de vitaminas B1 e B6 em Plasmodium falciparum e Mycobacterium tuberculosis, BP.DD
18/10150-3 - Observação e análise da SUMOlação das proteínas do Plasmodium falciparum durante estresse oxidativo, BP.IC
18/08820-0 - Inibidores da via de síntese de vitamina B6 entregues por associação com nanopartículas contra Plasmodium sp, BP.DR
17/26358-0 - Dissecção do metabolismo do ácido lipóico como target druggable na Malária, BP.DR
18/00562-2 - Exploração da vitamina B1 como pro-drug na Malária e MRSA, BP.IC
17/24901-8 - Estudos estruturais para a prospecção de agentes contra doenças infecciosas humanas, BP.DD - menos bolsas vinculadas
Assunto(s):Malária  Doenças transmissíveis  Receptores citoplasmáticos e nucleares  Análise estrutural  Desenvolvimento de fármacos  Plasmodium falciparum  Staphylococcus aureus 
Palavra(s)-Chave do Pesquisador:drug discovery | Infectious diseases | malária | Nuclear Receptors | structural analysis | transgenic modifications | Protozoologia de Parasitos

Resumo

Doenças infecciosas são uma ameaça a humanidade e atualmente seus agentes patogênicos estão se espalhando geograficamente devido à globalização e ao desenvolvimento de resistência às drogas disponíveis. A resistência aos fármacos disponíveis atualmente está ocorrendo em quase todos os patógenos e portanto há uma urgente necessidade de descobrir novo alvos terapêuticos e/ou novas classes de alvos. Neste projeto o foco será a descoberta de novos pró-fármacos explorando as vias de biossíntese das vitaminas B1/B6 dos patógenos humanos: Plasmodium falciparum, o parasita responsável por causar a malária severa, e a bactéria muti-resistente Staphylococcus aureus MRSA. Compostos serão identificados e desenhados de acordo com avaliações baseadas nas estruturas cristalográficas das respectivas enzimas envolvidas na biossíntese das vitaminas B1/B6, visando a incorporação dos compostos no metabolismo do patógeno. Portanto os novos compostos buscarão envenenar as enzimas dependentes das vitaminas como co-fatores. Ensaios complementares envolverão o uso de linhagens celulares humanas, assim como suas respectivas linhagens transgênicas super expressando receptores nucleares para xenobióticos, a fim de reportar possíveis interações com o hospedeiro. (AU)

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Publicações científicas (47)
(Referências obtidas automaticamente do Web of Science e do SciELO, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores)
LINZKE, MARLEEN; YAN, SUN LIU REI; TARNOK, ATTILA; ULRICH, HENNING; GROVES, MATTHEW R.; WRENGER, CARSTEN. Live and Let Dye: Visualizing the Cellular Compartments of the Malaria Parasite Plasmodium falciparum. Cytometry Part A, v. 97, n. 7, SI, . (12/50880-4, 17/03966-4, 15/26722-8, 14/23330-9, 17/26358-0, 12/50393-6)
DE PAULA, KARINA; SANTOS, JADEMILSON C.; MAFUD, ANA CAROLINA; NASCIMENTO, ALESSANDRO S.. Tetrazoles as PPAR gamma ligands: A structural and computational investigation. JOURNAL OF MOLECULAR GRAPHICS & MODELLING, v. 106, . (10/15376-8, 20/03983-9, 14/06565-2, 15/26722-8)
KRUGER, ARNE; ZIMBRES, FLAVIA M.; KRONENBERGER, THALES; WRENGER, CARSTEN. Molecular Modeling Applied to Nucleic Acid-Based Molecule Development. BIOMOLECULES, v. 8, n. 3, . (17/03966-4, 18/08820-0, 15/26722-8)
BARRA, ANGELICA LUANA C.; DANTAS, LIVIA DE OLIVEIRA C.; MORAO, LUANA GALVAO; GUTIERREZ, RAISSA F.; POLIKARPOV, IGOR; WRENGER, CARSTEN; NASCIMENTO, ALESSANDRO S.. Essential Metabolic Routes as a Way to ESKAPE From Antibiotic Resistance. FRONTIERS IN PUBLIC HEALTH, v. 8, . (15/13684-0, 17/18173-0, 15/26722-8)
MURAD, ALINE MELRO; BROGNARO, HEVILA; FALKE, SVEN; LINDNER, JASMIN; PERBANDT, MARKUS; MUDOGO, CELESTIN; SCHUBERT, ROBIN; WRENGER, CARSTEN; BETZEL, CHRISTIAN. Structure and activity of the DHNA Coenzyme-A Thioesterase from Staphylococcus aureus providing insights for innovative drug development. SCIENTIFIC REPORTS, v. 12, n. 1, p. 14-pg., . (17/03966-4, 12/12790-3, 15/26722-8)
BRIGANTI, LORENZO; CAPETTI, CAIO; PELLEGRINI, VANESSA O. A.; GHIO, SILVINA; CAMPOS, ELEONORA; NASCIMENTO, ALESSANDRO S.; POLIKARPOV, IGOR. Structural and molecular dynamics investigations of ligand stabilization via secondary binding site interactions in Paenibacillus xylanivorans GH11 xylanase. COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL, v. 19, p. 1557-1566, . (20/03983-9, 15/26722-8, 15/13684-0)
MORAO, LUANA G.; MANZINE, LIVIA R.; CLEMENTINO, LIVIA OLIVEIRA D.; WRENGER, CARSTEN; NASCIMENTO, ALESSANDRO S.. A scalable screening of E. coli strains for recombinant protein expression. PLoS One, v. 17, n. 7, p. 10-pg., . (17/24901-8, 17/03966-4, 15/26722-8, 19/20219-3, 20/03983-9)
MEISSNER, KAMILA ANNA; KRONENBERGER, THALES; MALTAROLLO, VINICIUS GONCALVES; GOULART TROSSINI, GUSTAVO HENRIQUE; WRENGER, CARSTEN. Targeting the Plasmodium falciparum plasmepsin V by ligand-based virtual screening. CHEMICAL BIOLOGY & DRUG DESIGN, v. 93, n. 3, p. 300-312, . (14/03644-9, 16/24790-9, 17/03966-4, 15/26722-8)
MINARI, KARINE; DE AZEVEDO, ERIKA CHANG; RODRIGUES KIRALY, VANESSA THOMAZ; HELENO BATISTA, FERNANDA APARECIDA; DE MORAES, FABIO ROGERIO; DE MELO, FERNANDO ALVES; NASCIMENTO, ALESSANDRO SILVA; GAVA, LISANDRA MARQUES; INACIO RAMOS, CARLOS HENRIQUE; BORGES, JULIO CESAR. Thermodynamic analysis of interactions of the Hsp90 with adenosine nucleotides: A comparative perspective. International Journal of Biological Macromolecules, v. 130, p. 125-138, . (15/26722-8, 13/25646-0, 17/18173-0, 11/23110-0, 14/07206-6, 12/50161-8, 09/53989-4, 17/07335-9)
REI YAN, SUN LIU; WAKASUQUI, FELIPE; DU, XIAOCHEN; GROVES, MATTHEW R.; WRENGER, CARSTEN. Lipoic Acid Metabolism as a Potential Chemotherapeutic Target Against Plasmodium falciparum and Staphylococcus aureus. RONTIERS IN CHEMISTR, v. 9, p. 7-pg., . (17/26358-0, 15/26722-8, 17/03966-4)
SCARPELLI, PEDRO H.; TESSARIN-ALMEIDA, GIULLIANA; VICOSO, KENIA LOPES; LIMA, WANIA REZENDE; BORGES-PEREIRA, LUCAS; MEISSNER, KAMILA ANNA; WRENGER, CARSTEN; RAFAELLO, ANNA; RIZZUTO, ROSARIO; POZZAN, TULLIO; et al. Melatonin activates FIS1, DYN1, and DYN2 Plasmodium falciparum related-genes for mitochondria fission: Mitoemerald-GFP as a tool to visualize mitochondria structure. Journal of Pineal Research, v. 66, n. 2, . (12/12807-3, 11/51295-5, 14/14347-5, 15/26722-8)
SOUZA JUNIOR, DOUGLAS RICARDO; MARTINS SILVA, AMANDA RIBEIRO; ROSA-FERNANDES, LIVIA; REIS, LORENNA ROCHA; ALEXANDRIA, GABRIELLY; BHOSALE, SANTOSH D.; GHILARDI, FABIO DE ROSE; DALCOQUIO, TALIA FALCAO; BERTOLIN, ADRIADNE JUSTI; NICOLAU, JOSE CARLOS; et al. HDL proteome remodeling associates with COVID-19 severity. JOURNAL OF CLINICAL LIPIDOLOGY, v. 15, n. 6, p. 796-804, . (15/26722-8, 16/00696-3, 20/04923-0, 19/25702-4, 17/07725-1, 18/15549-1, 18/18257-1, 13/07937-8)
GOMES, LAURA CORDEIRO; SANSON, MARINA CORDEIRO GOMES; BRAININ, PHILIP; DE MELO, MARIA DA CONCEICAO VIEIRA; DE SOUZA, RODRIGO MEDEIROS; MAZARO, JANAINA; LIMA, KARINE OLIVEIRA; RESENDE, JUNIA SILVA; VIEIRA, ISABELLE VICTORIA MARTINS; MESQUITA, EDINILSON DA SILVA; et al. Levels of hepatitis B antibody titers are affected by age and doses gap time in children from a high endemic area of the western Amazon. PLoS One, v. 16, n. 7, . (18/20468-0, 18/18257-1, 18/15549-1, 15/26722-8, 14/06863-3)
LAZARI, LUCAS C.; ZERBINATI, RODRIGO M.; ROSA-FERNANDES, LIVIA; SANTIAGO, VERONICA FEIJOLI; ROSA, KLAISE F.; ANGELI, CLAUDIA B.; SCHWAB, GABRIELA; PALMIERI, MICHELLE; SARMENTO, DMITY J. S.; MARINHO, CLAUDIO R. F.; et al. ALDI-TOF mass spectrometry of saliva samples as a prognostic tool for COVID-1. OURNAL OF ORAL MICROBIOLOG, v. 14, n. 1, . (18/15549-1, 20/06409-1, 20/04923-0, 18/18257-1, 15/26722-8, 17/03966-4, 21/07490-0, 18/20468-0)
BORGES-PEREIRA, LUCAS; MEISSNER, KAMILA ANNA; WRENGER, CARSTEN; GARCIA, CELIA R. S.. Plasmodium falciparum GFP-E-NTPDase expression at the intraerythrocytic stages and its inhibition blocks the development of the human malaria parasite. PURINERGIC SIGNALLING, v. 13, n. 3, p. 267-277, . (12/12807-3, 10/51593-3, 15/26722-8, 13/10288-1, 11/51295-5)
WUNDERLICH, GERHARD; BETZEL, CHRISTIAN; WRENGER, CARSTEN. Editorial: From Apicomplexan Genes to Drug Discovery. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 11, p. 2-pg., . (15/26722-8, 19/00899-0, 17/24267-7)
GAO, KAI; WANG, WENJIA; KRONENBERGER, THALES; WRENGER, CARSTEN; GROVES, MATTHEW R.. The Crystal Structure of the Plasmodium falciparum PdxK Provides an Experimental Model for Pro-Drug Activation. CRYSTALS, v. 9, n. 10, . (17/03966-4, 14/03644-9, 15/26722-8)
MACEDO-DA-SILVA, JANAINA; ROSA-FERNANDES, LIVIA; GOMES, VINICIUS DE MORAIS; SANTIAGO, VERONICA FEIJOLI; SANTOS, DEIVID MARTINS; MOLNAR, CATARINA MARIA STANISCHESK; BARBOZA, BRUNO RAFAEL; DE SOUZA, EDMARCIA ELISA; MARQUES, RODOLFO FERREIRA; BOSCARDIN, SILVIA BEATRIZ; et al. Protein Arginylation Is Regulated during SARS-CoV-2 Infection. Viruses-Basel, v. 15, n. 2, p. 25-pg., . (18/15549-1, 18/18257-1, 20/06409-1, 22/09915-0, 20/02988-7, 21/00140-3, 20/12277-0, 21/14179-9, 15/26722-8)
BOTOSSO, VIVIANE FONGARO; DURIGON, EDISON LUIZ; DE SOUZA, EDMARCIA ELISA. Emerging human viruses with pandemic potential: Diagnostics, pathogenesis, and therapeutics. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 13, p. 2-pg., . (20/12277-0, 21/11946-9, 15/26722-8)
ULLAH, NAJEEB; ANDALEEB, HINA; MUDOGO, CELESTIN NZANZU; FALKE, SVEN; BETZEL, CHRISTIAN; WRENGER, CARSTEN. Solution Structures and Dynamic Assembly of the 24-Meric Plasmodial Pdx1-Pdx2 Complex. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 21, n. 17, p. 16-pg., . (17/03966-4, 15/26722-8)
MONTEIRO JUNIOR, JULIO CESAR; KRUGER, ARNE; PALMISANO, GIUSEPPE; WRENGER, CARSTEN. Transporter-Mediated Solutes Uptake as Drug Target in Plasmodium falciparum. FRONTIERS IN PHARMACOLOGY, v. 13, p. 8-pg., . (15/26722-8, 18/15549-1, 18/18257-1, 18/08820-0, 20/04923-0)
SUMAM DE OLIVEIRA, DAFFINY; KRONENBERGER, THALES; PALMISANO, GIUSEPPE; WRENGER, CARSTEN; DE SOUZA, EDMARCIA ELISA. Targeting SUMOylation in Plasmodium as a Potential Target for Malaria Therapy. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 11, . (18/10150-3, 20/04923-0, 19/26771-0, 20/12277-0, 17/03966-4, 18/18257-1, 18/15549-1, 15/26722-8)
DOMBROWSKI, JAMILLE GREGORIO; BARATEIRO, ANDRE; MACHADO PEIXOTO, ERIKA PAULA; CLAUDIO DA SILVA BARROS, ANDRE BOLER; DE SOUZA, RODRIGO MEDEIROS; CLARK, TAANE GREGORY; CAMPINO, SUSANA; WRENGER, CARSTEN; WUNDERLICH, GERHARD; PALMISANO, GIUSEPPE; et al. Adverse pregnancy outcomes are associated with Plasmodium vivax malaria in a prospective cohort of women from the Brazilian Amazon. PLoS Neglected Tropical Diseases, v. 15, n. 4, . (17/03966-4, 17/03939-7, 18/18257-1, 19/12068-5, 15/26722-8, 17/24267-7, 20/06747-4, 18/20468-0, 20/04923-0, 18/15549-1, 17/05782-8)
PRATA, ISADORA OLIVEIRA; GALINDO CUBILLOS, ELIANA FERNANDA; KRUGER, ARNE; BARBOSA, DEIBS; MARTINS, JOAQUIM; SETUBAL, JOAO CARLOS; WUNDERLICH, GERHARD. Plasmodium falciparum Acetyl-CoA Synthetase Is Essential for Parasite Intraerythrocytic Development and Chromatin Modification. ACS INFECTIOUS DISEASES, v. 7, n. 12, p. 3224-3240, . (17/24267-7, 16/12659-5, 18/08820-0, 15/26722-8)
LUNEV, SERGEY; BUTZLOFF, SABINE; ROMERO, ATILIO R.; LINZKE, MARLEEN; BATISTA, FERNANDO A.; MEISSNER, KAMILA A.; MUELLER, INGRID B.; ADAWY, ALAA; WRENGER, CARSTEN; GROVES, MATTHEW R.. Oligomeric interfaces as a tool in drug discovery: Specific interference with activity of malate dehydrogenase of Plasmodium falciparum in vitro. PLoS One, v. 13, n. 4, . (12/12807-3, 14/23330-9, 13/10288-1, 16/24790-9, 15/26722-8)
BOSCH, SORAYA S.; LUNEV, SERGEY; BATISTA, FERNANDO A.; LINZKE, MARLEEN; KRONENBERGER, THALES; DOMLING, ALEXANDER S. S.; GROVES, MATTHEW R.; WRENGER, CARSTEN. Molecular Target Validation of Aspartate Transcarbamoylase from Plasmodium falciparum by Torin 2. ACS INFECTIOUS DISEASES, v. 6, n. 5, p. 986-999, . (17/03966-4, 15/26722-8, 13/17577-9, 14/23330-9)
WANG, MENGYING; BARRA, ANGELICA LUANA C.; BROGNARO, HEVILA; BETZEL, CHRISTIAN. Exploring Nucleation Pathways in Distinct Physicochemical Environments Unveiling Novel Options to Modulate and Optimize Protein Crystallization. CRYSTALS, v. 12, n. 3, p. 22-pg., . (18/21213-6, 15/26722-8, 19/26428-3)
REI YAN, SUN L.; WAKASUQUI, FELIPE; WRENGER, CARSTEN. Point-of-care tests for malaria: speeding up the diagnostics at the bedside and challenges in malaria cases detection. DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE, v. 98, n. 3, . (15/26722-8, 17/26358-0)
BATISTA, FERNANDO A.; BOSCH, SORAYA S.; BUTZLOFF, SABINE; LUNEV, SERGEY; MEISSNER, KAMILA A.; LINZKE, MARLEEN; ROMERO, ATILIO R.; WANG, CHAO; MUELLER, INGRID B.; DOMLING, ALEXANDER S. S.; et al. Oligomeric protein interference validates druggability of aspartate interconversion in Plasmodium falciparum. MICROBIOLOGYOPEN, v. 8, n. 7, . (17/03966-4, 15/26722-8, 16/24790-9, 14/23330-9, 13/17577-9)
DE AZEVEDO, ERIKA CHANG; NASCIMENTO, ALESSANDRO S.. Energy landscape of the domain movement in Staphylococcus aureus UDP-N-acetylglucosamine 2-epimerase. Journal of Structural Biology, v. 207, n. 2, p. 158-168, . (15/13684-0, 17/18173-0, 15/26722-8)
BATISTA, FERNANDO A.; GYAU, BENJAMIN; VILACHA, JULIANA F.; BOSCH, SORAYA S.; LUNEV, SERGEY; WRENGER, CARSTEN; GROVES, MATTHEW R.. New directions in antimalarial target validation. EXPERT OPINION ON DRUG DISCOVERY, v. 15, n. 2, p. 189-202, . (17/03966-4, 15/26722-8, 13/17577-9)
VASCONCELOS, STANLEY N. S.; MEISSNER, KAMILA A.; FERRAZ, WITOR R.; TROSSINI, GUSTAVO H. G.; WRENGER, CARSTEN; STEFANI, HELIO A.. Indole-3-glyoxyl tyrosine: synthesis and antimalarial activity against Plasmodium falciparum. Future Medicinal Chemistry, v. 11, n. 6, p. 525-538, . (13/17960-7, 12/12807-3, 15/26722-8, 12/00424-2, 17/25543-8, 16/24790-9)
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LUNEV, SERGEY; BOSCH, SORAYA S.; BATISTA, FERNANDO A.; WANG, CHAO; LI, JINGYAO; LINZKE, MARLEEN; KRUITHOF, PAUL; CHAMOUN, GEORGE; DOMLING, ALEXANDER S. S.; WRENGER, CARSTEN; et al. Identification of a non-competitive inhibitor of Plasmodium falciparum aspartate transcarbamoylase. Biochemical and Biophysical Research Communications, v. 497, n. 3, p. 835-842, . (15/26722-8, 13/17577-9, 14/23330-9)
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KRUGER, ARNE; DE JESUS SANTOS, ANA PAULA; DE SA, VANESSA; ULRICH, HENNING; WRENGER, CARSTEN. Aptamer Applications in Emerging Viral Diseases. PHARMACEUTICALS, v. 14, n. 7, . (18/07366-4, 15/26722-8, 17/03966-4, 15/26642-4)
PILLAT, MICHELI MAINARDI; KRUGER, ARNE; FERREIRA GUIMARAES, LARA MENDES; LAMEU, CLAUDIANA; DE SOUZA, EDMARCIA ELISA; WRENGER, CARSTEN; ULRICH, HENNING. Insights in Chloroquine Action: Perspectives and Implications in Malaria andCOVID-19. Cytometry Part A, v. 97, n. 9, . (18/07366-4, 18/08820-0, 15/26722-8, 15/19128-2)
LAZARI, LUCAS CARDOSO; GHILARDI, FABIO DE ROSE; ROSA-FERNANDES, LIVIA; ASSIS, DIEGO M.; NICOLAU, JOSE CARLOS; SANTIAGO, VERONICA FEIJOLI; DALCOQUIO, TALIA FALCAO; ANGELI, CLAUDIA B.; BERTOLIN, ADRIADNE JUSTI; MARINHO, CLAUDIO R. F.; et al. Prognostic accuracy of MALDI-TOF mass spectrometric analysis of plasma in COVID-19. LIFE SCIENCE ALLIANCE, v. 4, n. 8, . (20/04705-2, 18/15549-1, 17/03966-4, 15/26722-8, 18/20468-0, 20/04923-0, 18/18257-1)
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WANG, CHAO; KRUEGER, ARNE; DU, XIAOCHEN; WRENGER, CARSTEN; GROVES, MATTHEW R.. Novel Highlight in Malarial Drug Discovery: Aspartate Transcarbamoylase. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 12, p. 9-pg., . (18/08820-0, 15/26722-8)
SRINIVASAN, VASUNDARA; BROGNARO, HEVILA; PRABHU, PRINCE R.; DE SOUZA, EDMARCIA ELISA; GUENTHER, SEBASTIAN; REINKE, PATRICK Y. A.; LANE, THOMAS J.; GINN, HELEN; HAN, HUIJONG; EWERT, WIEBKE; et al. Antiviral activity of natural phenolic compounds in complex at an allosteric site of SARS-CoV-2 papain-like protease. COMMUNICATIONS BIOLOGY, v. 5, n. 1, p. 12-pg., . (15/26722-8, 19/00899-0, 20/12277-0)
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