Preprint / Version 1

Violacein, A Microbial Antiviral Product: Does Play Key Role as Active Agent Against SARS-CoV-2?

Authors

  • Nelson Duran Laboratory of Urogenital Carcinogenesis and Immunotherapy, Department of Structural and Functional Biology, University of Campinas
  • Giselle Z Justo Departamento de Ciências Farmacêuticas e Departamento de Bioquímica, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil
  • Gerson Nakazato Laboratory of Basic and Applied Bacteriology, Department of Microbiology, Biology Sciences Center, Universidade Estadual de Londrina (UEL), Londrina, PR, Brazil
  • Wagner J Fávaro Laboratory of Urogenital Carcinogenesis and Immunotherapy, Department of Structural and Functional Biology, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil

DOI:

https://doi.org/10.21467/preprints.315

Abstract

Violacein, a microbial product was characterized after continuous attempts to feature it, based on degradation and synthesis procedures, at the University of Liverpool (England), from 1958 to 1960 and only at 2001 was chemically synthesized. It is a quite known antimicrobial and antiviral natural product. New attempts to solve the infection caused by, or find the proper therapy for, COVID19, must adopt multidisciplinary approach. The aim of the current study is to address the targets, possible strategies and perspectives of new technologies and therapies on COVID19. It also hypothesizes the potential of using the therapeutic drug called violacein as multifunctional agent to treat patients at different COVID19 contamination stages. Our experience and knowledge about violacein has led us to extrapolate the potential use of this pigment.  Violacein multiple biological activities as also knowledge on its toxicity and antiviral activity enabled suggesting that it could be the new important agent used to treat COVID19.  Violacein is highly likely to act as protease inhibitor, at ACE2 receptor level and as immunotherapeutic drug against Covid19. In term of chemotherapy, it will be discussed the actual antiviral used against COVID19, such as, thalidomide, ivermectin and melatonin, among others.

Keywords:

Violacein, Antiviral, SARS-CoV-2, Immunology

Downloads

Download data is not yet available.

References

Boisbaudran, L. Matière colorante se format dans la calle de farine. Compt Rend Acad Sci 1882; 94: 562-567.

Bergonzini C. Um nuevo pigmento bacterio colorato. Ann Soc Natural, Modena Ser 1881; 2:149-158.

Zimmerman B. Review of Bergozini on Chromobacterium. Bot Cenrtralbl 1881; 4: 1528-1530.

Gessard C. On the blue and green coloration that appears on bandages. Compt Rend Hebdomadaires Seances de L´Acad Sci 1882; 94: 536-538.

De Moss R.D. Violacein. Antibiotics 1967; 2: 77-81.

Sneath PHA. Genus Chromobacterium Bergonzini 1881, 153AL, In NH Krieg, JG Holt eds., Bergey's Manual of Systematic Bacteriology, Vol. 1, Williams & Wilkins, Baltimore, 1984; p. 580-582.

Durán N, Menck CFM. Chromobacterium violaceum: a review of pharmacological and industrial perspectives. Crit Rev Microbiol. 2001; 27: 201-222.

Caldas LR. Photochemistry and photobiology in a virgin land. Photochem Photobiol.1077; 26: 1–2.

Caldas L.R. Um pigmento nas águas negras, Ciência Hoje 1990; 11, 56–57.

Ballantine JA, Beer RJS, Crutchley DJ, Dodd GM, Palmer DR. The chemistry of bacteria. Part VIII. The synthesis of violacein and related compounds. J Chem Soc 1960; 2292–2299.

Wille G, Steglich W. A short synthesis of the bacterial pigments violacein and deoxyviolacein. Synthesis 2001; 5: 759-762.

Azman A-S, Mawang C-I, Abubakar S. Bacterial pigments: The bioactivities and as an alternative for therapeutic applications. Nat Prod Commun 2018; 13: 1747-1754.

Choi SY, Yoon K-H, Lee JI, Mitchell RJ. Violacein: Properties and production of a versatile bacterial pigment. BioMed Res Inter 2015; 105: Article ID 465056.

Choi SY, Im H, Mitchell RJ. Violacein and bacterial predation: promising alternatives for priority multidrug resistant human pathogens. Future Microbiol 2017; 12: 835-838.

Choi SY, Lim S, Cho G, Kwon J, Mun W, Im H, et al. Chromobacterium violaceum delivers violacein, a hydrophobic antibiotic, to other microbes in membrane vesicles. Environ Microbiol 2020; 22: 705-713.

Dessaux Y, Elmerich C, Faure D. Violacein: a molecule of biological interest originating from the soil-borne bacterium Chromobacterium violaceum. Rev Méd Interne 2004; 25: 659-662.

Durán N, Justo, G.Z., Ferreira, C.V., Melo, P.S., Cordi, L., Martins, D. Violacein: properties and biological activities. Biotechnol Appl Biochem. 2007; 48: 127–133.

Durán M, Ponezi AN, Faljoni-Alario A, Teixeira MFS, Justo GZ, Durán N. Potential applications of violaceína: a microbial pigment. Med Chem Res 2012; 21: 1524-1532.

Durán N, Justo GZ, Durán M, Brocchi M, Cordi L, Tasic L, et al. Advances in Chromobacterium violaceum and properties of violacein?its main secondary metabolite: A review. Biotechnol Advan 2016; 34: 1030-1045.

Durán N, Fávaro WJ. The most prominents antiviral pharmaceutics against Covid-19 and their perspectives. Scielo Preprint Posted:2020-06-30.

Durán N, Fávaro WJ, Brocchi M, Justo GZ, Castro GR, Durán M, et al. Patents on violacein: A compound with great diversity of biological activities and industrial potential. Recent Patents Biotechnol 2021; DOI : 10.2174/2213476X07666201221111655.

Justo GZ, Durán N. Action and function of Chromobacterium violaceum in health and disease: Violacein as a promising metabolite to counteract gastroenterological diseases. Best Pract Res Clin Gastroenterol 2017; 31: 649-656.

Ramesh C, Vinithkumar NV, Kirubagaran R. Marine pigmented bacteria: A prospective source of antibacterial compounds. J Nat Sc Biol Med 2019; 10:104-113.

Venil CK, Dufossé L, Devi PR. Bacterial pigments: sustainable compounds with market potential for pharma and food industry. Front Sustain Food Syst 2020; 4:100.

Durán M, Faljoni-Alario A, Durán N. Chromobacterium violaceum and its important metabolites – review. Folia Microbiol 2010; 55: 535-547.

Kothari V, Sharma S, Padia D. Recent research advances on Chromobacterium violaceum. Asian Pacific J Trop Med 2017; 10: 744-752.

Numan M, Bashir S, Mumtaz R, Tayyab S, Rehman NU, Khan AL, et al. Therapeutic applications of bacterial pigments: a review of current status and future opportunities. Biotech 2018; 8: 207.

Haun M, Pereira MF, Hoffman ME, Joyas A, Campos V, Filardi LD, et al. Bacterial chemistry. VI. Biological activities and cytotoxicity of 1,3-dihydro-2H-indol-2-one derivatives. Biol Res 1992; 25: 21.

Melo PS, Maria SS, Vidal BC, Haun M, Durán N. Violacein cytotoxicity and induction of apoptosis in V79 cells. In Vitro Cell Dev Biol Anim 2000; 36: 539-543.

Bromberg N, Justo GZ, Haun M, Durán N, Ferreira CV. Violacein cytotoxicity on human blood lymphocytes and effect on phosphatases. J Enzyme Inhib Med Chem 2005; 20: 449-454.

Leal AM, de Queiroz JD, de Medeiros SR, Lima TK, Agnez-Lima LF. Violacein induces cell death by triggering mitochondrial membrane hyperpolarization in vitro. BMC Microbiol 2015;15: 115.

Pereira RS, Durán N, Volpe PLO. The use of violacein to study biochemical behaviour of Saccharomyces cerevisiee cells. Eur J Drug Metab Pharmacokinet 2005; 30: 225.

Cauz ACG. Carretero GPB, Saraiva GKV, Park P, Mortara L, Cuccovia IM, et al. Violacein Targets the Cytoplasmic Membrane of Bacteria. ACS Infect. Dis. 2019; 5: 539?549.

Andrighetti-Frohner CR, Ktatz JM, Antonio RV, Creczynski-Pasa TB, Barardi CRM, Simoes CMO. In vitro testing for genotoxicity of violacein assessed by Comet and Micronucleus assays. Mutation Res 2006; 603: 97.

Bromberg N, Dreyfuss JL, Regatieri CV, Palladino MV, Durán, N, Nader HB, et al. Growth inhibition and pro-apoptotic activity of violacein in Ehrlich ascites tumor. Chem Biol Interact 2010; 186: 43-52.

Pauer H, Hardoim CCP, Teixeira FL, Miranda KR, Barbirato DS, Pires de Carvalho DP, et al. Impact of violacein from Chromobacterium violaceum on the mammalian gut microbiome. Plos One 2018; 13: e0203748.

Antonisamy P, Ignacimuthu S. Immunomodulatory, analgesic and antipyretic effects of violacein isolated from Chromobacterium violaceum. Phytomedicine 2010; 17: 300–304.

Pang L, Antonisamy P, Esmail GA, Alzeer AF, Al-Dhabi NA, Arasu MV, et al. Nephroprotective effect of pigmented violacein isolated from Chromobacterium violaceum in wistar rats. Saudi J Biol Sci 2020; 27: 3307-3312.

Verinaud L, Lopes SCP, Prado ICN, Zanucoli F, da Costa TA, Di Gangi R, et al. Violacein Treatment Modulates Acute and Chronic Inflammation through the Suppression of Cytokine Production and Induction of Regulatory T Cells. PLoS ONE 2015; 10: e0125409.

May G, Lenk W, Ott H. Trans-hydroxyviolacein, process for preparing it pure and its use for the prophylaxis and therapy of viral diseases. Germany Patent. 1989; DE3813465 (A1).

May G, Brummer B, Ott H. Treatment of prophylaxis of polio and herpes virus infections - comprise administration of 3-(di:hydro-5-(hydroxy-1H- indolyl-2-oxo-3H-pyrrolidene)-di:hydro-2H-indole. Germany Patent. 1991; DE 3935066.

Andrighetti-Frohner CR, Antonio RV, Creczynski-Pasa TB, Barandi CRM, Simoes CMO. Cytotoxicity and potential antiviral evaluation of violacein produced by Chromobacterium violaceum. Mem Inst Oswaldo Cruz 2003; 98: 834–848.

Durán N, De Azevedo MBM, Alderete J. Formulation process of cyclodextrin/violacein for using as antibacterial, antitumoral, antiviral and trypanocide. Brazil Patent 1998; PIBr 9801307.

Alves OL, Gimenez IF, De Azevedo MMM, Durán N, Melo PS. Pharmacological use of cyclodextrine-Au-thiol-derivative/hydrophobic compound nanoparticles as antitumoral, antibacterial, antiviral and/or antiparasites, its obtention process and formulation. Brazil Pat 2005; PIBr 0502657-1.

Kallmayer V, Lanzendoerfer G, Meiring U, Mocigemba N, Reidel H, Schaefer J, et al. Cosmetic preparation, useful e.g. for the protection of skin and (semi)mucous membrane against bacteria and/or virus, comprises violacein dye in combination with lipophilic and/or hydrophilic substances. Germany Patent 2005; DE102005051869 A1.

Meiring U, Lanzendoerfer G, Riedel H, Kallmayer V, Viala S, Mocigemba N, et al. Cosmetic preparation, useful e.g. for the protection of skin and (semi)mucous membrane against bacteria and/or virus, comprises violacein dye in combination with lipophilic and/or hydrophilic substances. German Patent. 2007; DE102005051869 (A1).

Minbiole KPC, Harris R. Probiotic composition(s) and/or process(es) thereof. 2011; WO2011003062A3.

Martin PAW, Gundersen-Rindal D, Blackburn M, Buyer J. Chromobacterium subtsugae sp. nov., a betaproteobacterium toxic to Colorado potato beetle and other insect pests. Int J Syst Evol Microbiol 2007;57:993-999.

Blackburn MB, Sparks ME, Gundersen-Rindal DE. The genome of the insecticidal Chromobacterium subtsugae PRAA4-1 and its comparison with that of Chromobacterium violaceum ATCC 12472. Genom Data 2016;10:1–3.

Farrar RR, Gundersen-Rindal DE, Kuhar D, Blackburn MB. Insecticidal activity of Chromobacterium vaccinii. J Entomol Sci 2018; 53: 339-346.

Martin PA, Soby S. Insecticidal strains of Chromobacterium vaccinii sp. nov. for control of insects. USA Patent 2016; US 9339039 B1.

Vöing K, Harrison A, Soby SD. Draft genome sequence of Chromobacterium vaccinii, a potential biocontrol agent against mosquito (Aedes aegypti) larvae. Genome Announc 2015; 3: e00477-15.

Asolkar R, Huang H, Koivunen M, Marrone P. Chromobacterium bioactive compositions and metabolites. US Patent 2014; US8715754.

Asolkar R, Huang H, Koivunen M, Marrone P. Chromobacterium bioactive compositions and metabolites. US Patent 2016; US 20160095323 A1.

Tai W, He L, Zhang X, Pu J, Voronin D, Jiang S, et al. Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine. Cel Mol Immunol 2020; 17: 613-620.

Li S, Li S, Disoma C, Zheng R, Zhou M, Razzaq A, et al. SARS?CoV?2: Mechanism of infection and emerging technologies for future prospects. Rev Med Virol 2020; 2020: e2168.

Qiao B, de la Cruz MO. Enhanced binding of SARS-CoV 2 spike protein to receptor by distal polybasic cleavage sites. ACS Nano 2020; 14: 10616-10623.

Jin Z, Du X, Xu Y, Deng Y, Liu M, Zhao Y, et al. Structure of Mpro from COVID?19 virus and discovery of its inhibitors. Nature 2020; 582: 289-293.

Antony F, Vashi Y, Morla S. Therapeutic potential of nitazoxanide against Newcastle disease virus: A possible modulation of host cytokines. Cytokine 2020; 131: 155115.

Rossignol JF. Nitazoxanide, a new drug candidate for the treatment of Middle East respiratory syndrome coronavirus. J Infect Public Heal 2016; 9: 227-230.

Rocco PRM, Silva PL, Cruz FF, Junior MACM, Tierno PFGMM, Moura MA, et al. Early use of nitazoxanide in mild Covid-19 disease: randomised, placebo-controlled trial. Eur Respir J. 2021; doi: https://doi.org/10.1183/13993003.03725-2020).

Tabata C, Tabata R, Takahashi Y, Nakamura K, Nakano T. Thalidomide prevents cigarette smoke extract induced lung damage in mice. Inter Immunopharmacol 2015; 25: 511-517.

Chen C, Qi F, Shi K, Li Y, Li J, Chen Y, et al. Thalidomide combined with low-dose glucocorticoid in the treatment of COVID-19 Pneumonia. Preprints (www.preprints.org).| Posted: 26 February 2020.

Caly L, Druce JD, Catton MG, Jans, DA, Wagstaff KM. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res 2020; 178: 104787.

Kaur H, Shekhar N, Sharma S, Sarma P, Prakash A, Medhi B. Ivermectin as a potential drug for treatment of COVID 19: an in sync review with clinical and computational attributes. Pharmacol Rep 2021; https://doi.org/10.1007/s43440-020-00195-y.

Pandi-Perumal SR, Cardinali DP, Reiter RJ, Brown GM. Low melatonin as a contributor to SARS-CoV-2 disease. Melatonin Res 2020, 3: 558-576.

Fernandes PA, Kinker GS, Navarro BV, Jardim VC, Ribeiro-Paz ED, Córdoba-Moreno MO, et al. Melatonin-Index as a biomarker for predicting the distribution of presymptomatic and asymptomatic SARS-CoV-2 carriers. Melatonin Res 2021; 4: 189-205.

Martins D, Costa FTM, Brocchi M, Durán N. Evaluation of the antibacterial activity of poly-(D,L-lactide-co-glycolide) nanoparticles containing violacein. J Nanopart Res 2011; 13: 355-363.

Queiroz KCS, Milani R, Ruela-de-Sousa RF, Fuhler GM., Justo GZ, Zambuzzi SF, et al. Violacein induces death of resistant leukaemia cells via kinome reprogramming, endoplasmic reticulum stress and golgi apparatus collapse. PLoS ONE 2012; 7: e45362.

Platt D, Amara S, Mehta T, Vercuyssee K, Myles EL, Johnson G, et al. Violacein inhibits matrix metalloproteinase mediated CXCR4 expression: Potential anti-tumor effect in cancer invasion and metastasis. Biochem Biophys Res Commun 2014; 455: 107-112.

Meshram RJ, Bhiodaade NH, Gacche RN, Jamgle SN. Virtual screening and docking exploration on estrogen receptors: An in silico approach to decipher novel anticancer agents. Indian J Biotechmol 2012; 11: 389-395.

Downloads

Posted

2021-05-27

Section

Coronavirus

Categories