Strong anti-SARS-CoV-2 activity of Lucilia cuprina maggots’ excretion/secretion and its effect on viral entry and notch pathway in vitro: First work

Mohammad R. K. Abdel-Samad Fatma A. Taher Mahmoud Shehata Noura M. Abo Shama Ahmed Mostafa Mohamed A. Ali Iman H. Ibrahim   

Open Access   

Published:  Jun 19, 2022

Abstract

The global pandemic caused by SARS-CoV-2 requires new lines of treatment to hinder viral entry and pathogenesis. Lucilia cuprina maggots’ excretion/secretion (E/S) contains proteases and antioxidants, among other active ingredients that contribute to its antibacterial, antifungal, and antiviral activity. This study aims to assess the potential effects of E/S on the entry and molecular pathogenesis of a SARS-CoV-2 isolate “NRC-03-nhCoV” in vitro for the first time. E/S was obtained from the collected maggots of L. cuprina that were maintained under controlled laboratory conditions. The E/S was used to treat VERO-E6 cells infected with SARS-CoV-2. The predicted antiviral activity of the E/S and the expression of the Notch pathway and viral pathogenesis-related genes were assessed at three time points. E/S showed potential antiviral activity against SARS-CoV-2 (IC50 = 0.324 µg/ml) with a high selectivity index value (SI = 572.997). Serine protease present in E/S was predicted to interact with transmembrane protease, serine 2 and cathepsin B. E/S was able to significantly downregulate Notch-related genes, SUMO1, and TDG in SARS-CoV-2-infected cells, shifting their expression toward levels of the control. Therefore, E/S of L. cuprina maggots is a potential strong inhibitor for SARS-CoV-2.


Keyword:     SARS-CoV-2 TEMPRSS2 cathepsin B Notch pathway Lucilia cuprina maggots excretion/secretion.


Citation:

Abdel-Samad MRK, Taher FA, Shehata M, Abo Shama NM, Mostafa A, Ali MA, Ibrahim IH. Strong anti-SARS-CoV-2 activity of Lucilia cuprina maggots’ excretion/secretion and its effect on viral entry and notch pathway in vitro: First work. J Appl Pharm Sci, 2022; 12(07):122–130.

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

HTML Full Text

Reference

Abate G, Memo M, Uberti D. Impact of covid-19 on alzheimer's disease risk: viewpoint for research action. Healthc, 2020; 8(3):286. https://doi.org/10.3390/healthcare8030286

Abdel-Samad MRK. Antiviral and virucidal activities of Lucilia cuprina maggots' excretion/secretion (Diptera: Calliphoridae): first work. Heliyon, 2019; 5(11):e02791. https://doi.org/10.1016/j.heliyon.2019.e02791

Adachi S, Jigami T, Yasui T, Nakano T, Ohwada S, Omori Y, Sugano S, Ohkawara B, Shibuya H, Nakamura T, Akiyama T. Role of a BCL9-related β-catenin-binding protein, B9L, in tumorigenesis induced by aberrant activation of Wnt signaling. Cancer Res, 2004; 64(23):8496-501. PMid:15574752. https://doi.org/10.1158/0008-5472.CAN-04-2254

Baril M, Es-Saad S, Chatel-Chaix L, Fink K, Pham T, Raymond VA, Audette K, Guenier AS, Duchaine J, Servant M, Bilodeau M, Cohen É, Grandvaux N, Lamarre D. Genome-wide RNAi screen reveals a new role of a WNT/CTNNB1 signaling pathway as negative regulator of virusinduced innate immune responses. PLoS Pathog, 2013; 9(6):e1003416. PMid:23785285. https://doi.org/10.1371/journal.ppat.1003416

Breikaa RM, Lilly B. The Notch pathway: a link between COVID-19 pathophysiology and its cardiovascular complications. Front Cardiovasc Med, 2021; 0:528. https://doi.org/10.3389/fcvm.2021.681948

Casu RE, Pearson RD, Jarmey JM, Cadogan LC, Riding GA, Tellam RL. Excretory/secretory chymotrypsin from Lucilia cuprina: purification, enzymatic specificity and amino acid sequence deduced from mRNA. Insect Mol Biol, 1994; 3(4):201-11. PMid:7704304. https://doi.org/10.1111/j.1365-2583.1994.tb00168.x

Chambers L, Woodrow S, Brown AP, Harris PD, Phillips D, Hall M, Church JCT, Pritchard DI. Degradation of extracellular matrix components by defined proteinases from the greenbottle larva Lucilia sericata used for the clinical debridement of non-healing wounds. Br J Dermatol, 2003; 148 (1):14-23. PMid:12534589. https://doi.org/10.1046/j.1365-2133.2003.04935.x

Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, Xia J, Yu T, Zhang X, Zhang L. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet, 2020; 395(10223):507-13. PMid:32007143. https://doi.org/10.1016/S0140-6736(20)30211-7

De Strooper B, Iwatsubo T, Wolfe MS. Presenilins and γ-secretase: structure, function, and role in Alzheimer disease. Cold Spring Harb Perspect Med, 2012; 2(1):a006304. PMid:22315713. https://doi.org/10.1101/cshperspect.a006304

Feng Y, Zhao M, He Z, Chen Z, Sun L. Research and utilization of medicinal insects in China. Entomol Res, 2009; 39(5):313-6. https://doi.org/10.1111/j.1748-5967.2009.00236.x

Feoktistova M, Geserick P, Leverkus M. Crystal violet assay for determining viability of cultured cells. Cold Spring Harb Protoc, 2016; 2016(4):343-6. PMid:27037069. https://doi.org/10.1101/pdb.prot087379

Gupta A. A review of the use of maggots in wound therapy. Ann Plast Surg, 2008; 60(2):224-7. PMid:18216520. https://doi.org/10.1097/SAP.0b013e318053eb5e

Hassan MI, Hammad KM, Fouda MA, Kamel MR. The using of Lucilia cuprina maggots in the treatment of diabetic foot wounds. J Egypt Soc Parasitol, 2014; 44(1):125-9. https://doi.org/10.21608/jesp.2014.90716

Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, Müller MA, Drosten C, Pöhlmann S. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell, 2020; 181(2):271-80.e8. PMid:32142651. https://doi.org/10.1016/j.cell.2020.02.052

Ibrahim IH, Ellakwa DES. SUMO pathway, blood coagulation and oxidative stress in SARS-CoV-2 infection. Biochem Biophys Reports, 2021; 26:100938. PMid:33558851. https://doi.org/10.1016/j.bbrep.2021.100938

Ito T, Allen RM, Carson IV WF, Schaller M, Cavassani KA, Hogaboam CM, Lukacs NW, Matsukawa A, Kunkel SL. The critical role of Notch ligand delta-like 1 in the pathogenesis of influenza a virus (H1N1) infection. PLoS Pathog, 2011; 7(11):e1002341. PMid:22072963. https://doi.org/10.1371/journal.ppat.1002341

Jacobs AL, Schär P. DNA glycosylases: in DNA repair and beyond. Chromosoma, 2012; 121(1):1-20. PMid:22048164. https://doi.org/10.1007/s00412-011-0347-4

Jiang KC, Sun XJ, Wang W, Liu L, Cai Y, Chen YC, Luo N, Yu JH, Cai DY, Wang AP. Excretions/secretions from bacteria-pretreated maggot are more effective against Pseudomonas aeruginosa Biofilms. PLoS One, 2012; 7(11):e49815. PMid:23226221. https://doi.org/10.1371/journal.pone.0049815

journal.pone.0049815 Kandeil A, Mostafa A, El-Shesheny R, Shehata M, Roshdy WH, Ahmed SS, Gomaa M, Taweel AE, Kayed AE, Mahmoud SH, Moatasim Y. Coding-complete genome sequences of two SARS-CoV-2 isolates from Egypt. Microbiol Resour Announc, 2020; 9(22). PMid:32467284. https://doi.org/10.1128/MRA.00489-20

Kandeil A, Mostafa A, Hegazy RR, El-Shesheny R, Taweel A El, Gomaa MR, Shehata M, Elbaset MA, Kayed AE, Mahmoud SH, Moatasim Y, Kutkat O, Yassen NN, Shabana ME, Gaballah M, Kamel MN, Shama NMA, Sayes M El, Ahmed AN, Elalfy ZS, Mohamed BMSA, Abd El-Fattah SN, Hariri HM El, Kader MA, Azmy O, Kayali G, Ali MA. Immunogenicity and safety of an inactivated sars-cov-2 vaccine: preclinical studies. Vaccines, 2021; 9(3):1-15. https://doi.org/10.3390/vaccines9030214

Kawase M, Shirato K, van der Hoek L, Taguchi F, Matsuyama S. Simultaneous treatment of human bronchial epithelial cells with serine and cysteine protease inhibitors prevents severe acute respiratory syndrome coronavirus entry. J Virol, 2012; 86(12):6537-45. PMid:22496216. https://doi.org/10.1128/JVI.00094-12

Keewan E, Naser SA. The role of notch signaling in macrophages during inflammation and infection: implication in rheumatoid arthritis? Cells, 2020; 9(1):111. PMid:31906482. https://doi.org/10.3390/cells9010111

Khare P, Sahu U, Pandey SC, Samant M. Current approaches for target-specific drug discovery using natural compounds against SARSCoV-2 infection. Virus Res, 2020; 290:198169. PMid:32979476. https://doi.org/10.1016/j.virusres.2020.198169

Lescure FX, Bouadma L, Nguyen D, Parisey M, Wicky PH, Behillil S, Gaymard A, Bouscambert-Duchamp M, Donati F, Le Hingrat Q, Enouf V, Houhou-Fidouh N, Valette M, Mailles A, Lucet JC, Mentre F, Duval X, Descamps D, Malvy D, Timsit JF, Lina B, van-der-Werf S, Yazdanpanah Y. Clinical and virological data of the first cases of COVID-19 in Europe: a case series. Lancet Infect Dis, 2020; 20(6):697-706. PMid:32224310. https://doi.org/10.1016/S1473-3099(20)30200-0

Loram A. Book review: the insects: an outline of entomology. J Insect Conserv, 2006; 10(1):81-2. https://doi.org/10.1007/s10841-005-8782-2

Lowrey AJ, Cramblet W, Bentz GL. Viral manipulation of the cellular sumoylation machinery. Cell Commun Signal, 2017; 15(1). PMid:28705221. https://doi.org/10.1186/s12964-017-0183-0

Lu Y, Zhang Y, Xiang X, Sharma M, Liu K, Wei J, Shao D, Li B, Tong G, Olszewski MA, Ma Z, Qiu Y. Notch signaling contributes to the expression of inflammatory cytokines induced by highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) infection in porcine alveolar macrophages. Dev Comp Immunol, 2020; 108:103690. PMid:32222356. https://doi.org/10.1016/j.dci.2020.103690

Mahmoud DB, Shitu Z, Mostafa A. Drug repurposing of nitazoxanide: can it be an effective therapy for COVID-19? J Genet Eng Biotechnol, 2020; 18(1). PMid:32725286. https://doi.org/10.1186/s43141-020-00055-5

Masucci MG. Viral ubiquitin and ubiquitin-like deconjugases- swiss army knives for infection. Biomolecules, 2020; 10(8):1-24. PMid:32752270. https://doi.org/10.3390/biom10081137

Mehedi M, McCarty T, Martin SE, Le Nouën C, Buehler E, Chen YC, Smelkinson M, Ganesan S, Fischer ER, Brock LG, Liang B, Munir S, Collins PL, Buchholz UJ. Actin-related protein 2 (ARP2) and virus-induced filopodia facilitate human respiratory syncytial virus spread. PLoS Pathog, 2016; 12(12):e1006062. PMid:27926942. https://doi.org/10.1371/journal.ppat.1006062

Mostafa A, Kandeil A, Elshaier YAMM, Kutkat O, Moatasim Y, Rashad AA, Shehata M, Gomaa MR, Mahrous N, Mahmoud SH, Gaballah M, Abbas H, Taweel A El, Kayed AE, Kamel MN, Sayes M El, Mahmoud DB, El-Shesheny R, Kayali G, Ali MA. Fda-approved drugs with potent in vitro antiviral activity against severe acute respiratory syndrome coronavirus 2. Pharmaceuticals, 2020; 13(12):1-24. https://doi.org/10.3390/ph13120443

Murakami Y, Mizuguchi K. Homology-based prediction of interactions between proteins using Averaged One-Dependence Estimators. BMC Bioinform, 2014; 15(1). PMid:24953126. https://doi.org/10.1186/1471-2105-15-213

Nigam Y, Bexfield A, Thomas S, Ratcliffe NA. Maggot therapy: the science and implication for CAM Part I - History and bacterial resistance. Evid Based Compl Altern Med, 2006; 3(2):223-7. https://doi.org/10.1093/ecam/nel021

Padmanabhan P, Desikan R, Dixit NM. Targeting TMPRSS2 and Cathepsin B/L together may be synergistic against SARSCoV- 2 infection. PLoS Comput Biol, 2020; 16(12):e1008461. PMid:33290397. https://doi.org/10.1371/journal.pcbi.1008461

Payne S. Methods to study viruses. Viruses, 2017: 37-52. https://doi.org/10.1016/B978-0-12-803109-4.00004-0

Petersen H, Mostafa A, Tantawy MA, Iqbal AA, Hoffmann D, Tallam A, Selvakumar B, Pessler F, Beer M, Rautenschlein S, Pleschka S. NS segment of a 1918 influenza a virus-descendent enhances replication of H1N1pdm09 and virus-induced cellular immune response in mammalian and avian systems. Front Microbiol, 2018; 9(MAR). https://doi.org/10.3389/fmicb.2018.00526

Pöppel AK, Koch A, Kogel KH, Vogel H, Kollewe C, Wiesner J, Vilcinskas A. Lucimycin, an antifungal peptide from the therapeutic maggot of the common green bottle fly Lucilia sericata. Biol Chem, 2014; 395(6):649-56. PMid:24622788. https://doi.org/10.1515/hsz-2013-0263

Pytel D, S?upianek A, Ksiazek D, Skórski T, B?asiak J. UracilDNA glycosylases. Postepy Biochem, 2008; 54(4):362-70. PMid:19248582; http//doi.org/10.1016/b978-0-12-821067-3.00039-8

Ragia G, Manolopoulos VG. Inhibition of SARS-CoV-2 entry through the ACE2/TMPRSS2 pathway: a promising approach for uncovering early COVID-19 drug therapies. Eur J Clin Pharmacol, 2020; 76(12):1623-30. PMid:32696234. https://doi.org/10.1007/s00228-020-02963-4

Rizzo P, Vieceli Dalla Sega F, Fortini F, Marracino L, Rapezzi C, Ferrari R. COVID-19 in the heart and the lungs: could we "Notch" the inflammatory storm? Basic Res Cardiol, 2020; 115(3). PMid:32274570. https://doi.org/10.1007/s00395-020-0791-5

Ryu HY. SUMO: a novel target for anti-coronavirus therapy. Pathog Glob Health, 2021:1-8.

Sherman RA. Maggot therapy takes us back to the future of wound care: new and improved maggot therapy for the 21st century. J Diabetes Sci Technol, 2009; 3(2):336-44. PMid:20144365. https://doi.org/10.1177/193229680900300215

Smet-Nocca C, Wieruszeski JM, Léger H, Eilebrecht S, Benecke A. SUMO-1 regulates the conformational dynamics of ThymineDNA Glycosylase regulatory domain and competes with its DNA binding activity. BMC Biochem, 2011; 12(1):4. PMid:21284855. https://doi.org/10.1186/1471-2091-12-4

Steinacher R, Barekati Z, Botev P, Ku?nierczyk A, Slupphaug G, Schär P. SUMOylation coordinates BERosome assembly in active DNA demethylation during cell differentiation. EMBO J, 2019; 38(1). PMid:30523148. https://doi.org/10.15252/embj.201899242

Swaine T, Dittmar MT. CDC42 use in viral cell entry processes by RNA viruses. Viruses, 2015; 7(12):6526-36. PMid:26690467. https://doi.org/10.3390/v7122955

Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, HuertaCepas J, Simonovic M, Doncheva NT, Morris JH, Bork P, Jensen LJ, Von Mering C. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res, 2019; 47(D1):D607-13. PMid:30476243. https://doi.org/10.1093/nar/gky1131

Thompson PK, Zúñiga-Pflücker JC. On becoming a T cell, a convergence of factors kick it up a Notch along the way. Semin Immunol, 2011; 23(5):350-9. PMid:21981947. https://doi.org/10.1016/j.smim.2011.08.007

Tomita T. Probing the structure and function relationships of presenilin by substituted-cysteine accessibility method. Meth Enzymol, 2017; 584:185-205. PMid:28065263. https://doi.org/10.1016/bs.mie.2016.10.033

Turshudzhyan A. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced cardiovascular syndrome: etiology, outcomes, and management. Cureus, 2020; 12:e8543. https://doi.org/10.7759/cureus.8543

Vastrad B, Vastrad C, Tengli A. Identification of potential mRNA panels for severe acute respiratory syndrome coronavirus 2 (COVID-19) diagnosis and treatment using microarray dataset and bioinformatics methods. 3 Biotech, 2020; 10(10):422. https://doi.org/10.1007/s13205-020-02406-y

Van der Plas MJA, Jukema GN, Wai SW, Dogterom-Ballering HCM, Lagendijk EI, Van Gulpen C, Van Dissel JT, Bloemberg G V., Nibbering PH. Maggot excretions/secretions are differentially effective against biofilms of Staphylococcus aureus and Pseudomonas aeruginosa. J Antimicrob Chemother, 2008; 61(1):117-22. PMid:17965032. https://doi.org/10.1093/jac/dkm407

Vieceli Dalla Sega F, Fortini F, Aquila G, Campo G, Vaccarezza M, Rizzo P. Notch signaling regulates immune responses in atherosclerosis. Front Immunol, 2019; 10(MAY). PMid:31191522. https://doi.org/10.3389/fimmu.2019.01130

Vistnes LM, Lee R, Ksander GA. Proteolytic activity of blowfly larvae secretions in experimental burns. Surgery, 1981; 90(5):835-41. PMid:7029766.

Woodby BL, Songock WK, Scott ML, Raikhy G, Bodily JM. Induction of interferon kappa in human papillomavirus 16 infection by transforming growth factor beta-induced promoter demethylation. J Virol, 2018; 92(8):e01714-7. PMid:29437968. https://doi.org/10.1128/JVI.01714-17

Zhang C, Wu Z, Li JW, Zhao H, Wang GQ. Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality. Int J Antimicrob Agents, 2020; 55(5):105954. PMid:32234467. https://doi.org/10.1016/j.ijantimicag.2020.105954

Zhou M, Cui Z lei, Guo X jun, Ren L pin, Yang M, Fan Z wen, Han R chao, Xu W guo. Blockade of Notch signalling by γ-secretase inhibitor in lung T cells of asthmatic mice affects T cell differentiation and pulmonary inflammation. Inflammation, 2015; 38(3):1281-8. PMid:25586485. https://doi.org/10.1007/s10753-014-0098-5

Article Metrics

8 Absract views 0 PDF Downloads 8 Total views

   Abstract      Pdf Download

Related Search

By author names

Citiaion Alert By Google Scholar

Name Required
Email Required Invalid Email Address

Comment required