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Horm Metab Res 2024; 56(04): 308-317
DOI: 10.1055/a-2173-0277
Original Article: Endocrine Research

Marine Sponge-Derived Secondary Metabolites Modulate SARS-CoV-2 Entry Mechanisms

Charlotte Steenblock 
1   Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
,
Stefanie Richter
2   Institute of Medical Microbiology and Virology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
,
Dirk Lindemann
2   Institute of Medical Microbiology and Virology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
,
Hermann Ehrlich
3   Center for Advanced Technologies, Adam Mickiewicz University, Poznan, Poland
,
Stefan R. Bornstein
1   Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
4   School of Cardiovascular and Metabolic Medicine and Sciences, Faculty of Life Sciences & Medicine, King’s College London, London, United Kingdom of Great Britain and Northern Ireland
5   Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), Zürich, Switzerland
,
Nicole Bechmann
6   Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany
› Author Affiliations Funding Information The State Parliament of the Free State of Saxony — 100537675, TP2 Deutsche Forschungsgemeinschaft — 314061271; 288034826
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Abstract

The emergence of SARS-CoV 2 caused the COVID-19 pandemic, resulting in numerous global infections and deaths. In particular, people with metabolic diseases display an increased risk of severe COVID 19 and a fatal outcome. Treatment options for severe cases are limited, and the appearance of new virus variants complicates the development of novel therapies. To better manage viral infections like COVID 19, new therapeutic approaches are needed. Marine sponges offer a natural and renewable source of unique bioactive agents. These sponges produce secondary metabolites with various effects, including anti-viral, anti-inflammatory, and anti-tumorigenic properties. In the current study, we investigated the effect of five different marine sponge-derived secondary metabolites (four bromotyrosines and one sesquiterpenoid hydroquinone). Two of these, Avarol and Acetyl-dibromoverongiaquinol reduced the expression of ACE2, the main receptor for SARS-CoV 2, and the alternative receptor NRP1. Moreover, these substances derived from sponges demonstrated the ability to diminish the virus titer in SARS-CoV 2-infected cells, especially concerning the Omicron lineage. However, the reduction was not substantial enough to expect a significant impact on infected humans. Consequently, the investigated sponge-derived secondary metabolites are not likely to be effective to treat COVID 19 as a stand-alone therapy.

Key words

marine sponges - Aplysina cavernicola - COVID-19 - SARS-CoV-2 - viral infections - bromotyrosines

Supplementary Material



Publication History

Received: 28 July 2023

Accepted after revision: 01 September 2023

Article published online:
04 October 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Steenblock C, Hassanein M, Khan EG. et al. Obesity and COVID-19: what are the consequences?. Horm Metab Res 2022; 54: 496-502
    Google Scholar
  • 2 Steenblock C, Hassanein M, Khan EG. et al. Diabetes and COVID-19: short- and long-term consequences. Horm Metab Res 2022; 54: 503-509
    Google Scholar
  • 3 Bechmann N, Barthel A, Schedl A. et al. Sexual dimorphism in COVID-19: potential clinical and public health implications. Lancet Diabetes Endocrinol 2022; 10: 221-230
    Google Scholar
  • 4 Romero Starke K, Reissig D, Petereit-Haack G. et al. The isolated effect of age on the risk of COVID-19 severe outcomes: a systematic review with meta-analysis. BMJ Glob Health 2021; 6: e006434
    Google Scholar
  • 5 Chenchula S, Vidyasagar K, Pathan S. et al. Global prevalence and effect of comorbidities and smoking status on severity and mortality of COVID-19 in association with age and gender: a systematic review, meta-analysis and meta-regression. Sci Rep 2023; 13: 6415
    Google Scholar
  • 6 Binnewerg B, Schubert M, Voronkina A. et al. Marine biomaterials: biomimetic and pharmacological potential of cultivated Aplysina aerophoba marine demosponge. Mater Sci Eng C Mater Biol Appl 2020; 109: 110566
    Google Scholar
  • 7 Kovalchuk V, Voronkina A, Binnewerg B. et al. Naturally drug-loaded chitin: isolation and applications. Mar Drugs 2019; 17: 574
    Google Scholar
  • 8 Muzychka L, Voronkina A, Kovalchuk V. et al. Marine biomimetics: bromotyrosines loaded chitinous skeleton as source of antibacterial agents. Appl Phys A Mater Sci Process 2021; 127: 15
    Google Scholar
  • 9 Geahchan S, Ehrlich H, Rahman MA. The anti-viral applications of marine resources for COVID-19 treatment: an overview. Mar Drugs 2021; 19: 409
    Google Scholar
  • 10 Alcaraz MJ, Payá M. Marine sponge metabolites for the control of inflammatory diseases. Curr Opin Investig Drugs 2006; 7: 974-979
    Google Scholar
  • 11 Keyzers RA, Davies-Coleman MT. Anti-inflammatory metabolites from marine sponges. Chem Soc Rev 2005; 34: 355-365
    Google Scholar
  • 12 Bechmann N, Ehrlich H, Eisenhofer G. et al. Anti-tumorigenic and anti-metastatic activity of the sponge-derived marine drugs aeroplysinin-1 and isofistularin-3 against pheochromocytoma in vitro. Mar Drugs 2018; 16: 172
    Google Scholar
  • 13 Drechsel A, Helm J, Ehrlich H. et al. Anti-tumor activity vs. normal cell toxicity: therapeutic potential of the bromotyrosines aerothionin and homoaerothionin in vitro. Mar Drugs 2020; 18: 236
    Google Scholar
  • 14 Geahchan S, Ehrlich H, Rahman A. A short overview: marine resources as potential interventions for the Omicron SARS-CoV-2 variant. COVID 2022; 2: 501-512
    Google Scholar
  • 15 Yang Y, Li J, Han F. Focus on marine animal safety and marine bioresources in response to the SARS-CoV-2 crisis. Int J Mol Sci 2022; 23: 15136
    Google Scholar
  • 16 Ferrucci V, Kong DY, Asadzadeh F. et al. Long-chain polyphosphates impair SARS-CoV-2 infection and replication. Sci Signal 2021; 14: eabe5040
    Google Scholar
  • 17 Müller WEG, Neufurth M, Schepler H. et al. The biomaterial polyphosphate blocks stoichiometric binding of the SARS-CoV-2 S-protein to the cellular ACE2 receptor. Biomater Sci 2020; 8: 6603-6610
    Google Scholar
  • 18 Müller WEG, Neufurth M, Wang S. et al. Morphogenetic (mucin expression) as well as potential anti-corona viral activity of the marine secondary metabolite polyphosphate on A549 cells. Mar Drugs 2020; 18: 639
    Google Scholar
  • 19 Neufurth M, Wang X, Tolba E. et al. The inorganic polymer, polyphosphate, blocks binding of SARS-CoV-2 spike protein to ACE2 receptor at physiological concentrations. Biochem Pharmacol 2020; 182: 114215
    Google Scholar
  • 20 Gentile D, Patamia V, Scala A. et al. Putative inhibitors of SARS-CoV-2 main protease from a library of marine natural products: a virtual screening and molecular modeling study. Mar Drugs 2020; 18: 225
    Google Scholar
  • 21 Khan MT, Ali A, Wang Q. et al. Marine natural compounds as potents inhibitors against the main protease of SARS-CoV-2-a molecular dynamic study. J Biomol Struct Dyn 2021; 39: 3627-3637
    Google Scholar
  • 22 Zahran EM, Albohy A, Khalil A. et al. Bioactivity potential of marine natural products from scleractinia-associated microbes and in silico anti-SARS-COV-2 evaluation. Mar Drugs 2020; 18: 645
    Google Scholar
  • 23 Steenblock C, Richter S, Berger I. et al. Viral infiltration of pancreatic islets in patients with COVID-19. Nat Commun 2021; 12: 3534
    Google Scholar
  • 24 Steenblock C, Toepfner N, Beuschlein F. et al. SARS-CoV-2 infection and its effects on the endocrine system. Best Pract Res Clin Endocrinol Metab 2023; 101761
    Google Scholar
  • 25 Stadtmüller M, Laubner A, Rost F. et al. Emergence and spread of a sub-lineage of SARS-CoV-2 alpha variant B.1.1.7 in Europe, and with further evolution of spike mutation accumulations shared with the beta and gamma variants. Virus Evolution 2022; 8: veac010
    Google Scholar
  • 26 Matsuyama S, Nao N, Shirato K. et al. Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells. Proc Natl Acad Sci U S A 2020; 117: 7001-7003
    Google Scholar
  • 27 Cantuti-Castelvetri L, Ojha R, Pedro LD. et al. Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity. Science 2020; 370: 856-860
    Google Scholar
  • 28 Rangu R, Wander PL, Barrow BM. et al. Going viral in the islet: mediators of SARS-CoV-2 entry beyond ACE2. J Mol Endocrinol 2022; 69: R63-R79
    Google Scholar
  • 29 Sebastián-Martín A, Sánchez BG, Mora-Rodríguez JM. et al. Role of dipeptidyl peptidase-4 (DPP4) on COVID-19 physiopathology. Biomedicines 2022; 10: 2026
    Google Scholar
  • 30 Wei J, Alfajaro MM, DeWeirdt PC. et al. Genome-wide CRISPR screens reveal host factors critical for SARS-CoV-2 infection. Cell 2021; 184: 76-91 e13
    Google Scholar
  • 31 Wei J, Patil A, Collings CK. et al. Pharmacological disruption of mSWI/SNF complex activity restricts SARS-CoV-2 infection. Nat Genet 2023; 55: 471-483
    Google Scholar
  • 32 Hu TY, Frieman M, Wolfram J. Insights from nanomedicine into chloroquine efficacy against COVID-19. Nat Nanotechnol 2020; 15: 247-249
    Google Scholar
  • 33 Vincent MJ, Bergeron E, Benjannet S. et al. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J 2005; 2: 69
    Google Scholar
  • 34 Savarino A, Boelaert JR, Cassone A. et al. Effects of chloroquine on viral infections: an old drug against today’s diseases?. Lancet Infect Dis 2003; 3: 722-727
    Google Scholar
  • 35 Harmer D, Gilbert M, Borman R. et al. Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme. FEBS Lett 2002; 532: 107-110
    Google Scholar
  • 36 Li MY, Li L, Zhang Y. et al. Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues. Infect Dis Poverty 2020; 9: 45
    Google Scholar
  • 37 Huang Y, Wang Y, Xu D. et al. Characterization of the SARS-CoV-2 co-receptor NRP1 expression profiles in healthy people and cancer patients: Implication for susceptibility to COVID-19 disease and potential therapeutic strategy. Front Genet 2022; 13: 995736
    Google Scholar
  • 38 Soll D, Beer F, Spranger L. et al. Effects of weight loss on adipose and muscular neuropilin 1 mRNA expression in obesity: potential implication in SARS-CoV-2 infections?. Obes Facts 2022; 15: 90-98
    Google Scholar
  • 39 Oz M, Lorke DE, Kabbani N. A comprehensive guide to the pharmacologic regulation of angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor. Pharmacol Ther 2021; 221: 107750
    Google Scholar
  • 40 Ghosh S, Das S, Ahmad I. et al. In silico validation of anti-viral drugs obtained from marine sources as a potential target against SARS-CoV-2 Mpro. Journal of the Indian Chemical Society 2021; 98: 100272
    Google Scholar
  • 41 Kuchino Y, Nishimura S, Schroder HC. et al. Selective inhibition of formation of suppressor glutamine tRNA in Moloney murine leukemia virus-infected NIH-3T3 cells by Avarol. Virology 1988; 165: 518-526
    Google Scholar
  • 42 Müller WE, Schröder HC, Reuter P. et al. Inhibition of expression of natural UAG suppressor glutamine tRNA in HIV-infected human H9 cells in vitro by Avarol. AIDS Res Hum Retroviruses 1988; 4: 279-286
    Google Scholar
  • 43 GÓMez-Archila LG, Zapata W, Galeano E. et al. Bromotyrosine derivatives from marine sponges inhibit the HIV-1 replication in vitro. Vitae 2014; 21: 114-125
    Google Scholar
  • 44 Iwata-Yoshikawa N, Kakizaki M, Shiwa-Sudo N. et al. Essential role of TMPRSS2 in SARS-CoV-2 infection in murine airways. Nat Commun 2022; 13: 6100
    Google Scholar
  • 45 Rosli SNZ, Dimeng SR, Shamsuddin F. et al. Vero CCL-81 and Calu-3 cell lines as alternative hosts for isolation and propagation of SARS-CoV-2 isolated in Malaysia. Biomedicines 2023; 11: 1658
    Google Scholar
  • 46 Lau EHY, Tsang OTY, Hui DSC. et al. Neutralizing antibody titres in SARS-CoV-2 infections. Nature Communications 2021; 12: 63
    Google Scholar
  • 47 Wolf JM, Wolf LM, Bello GL. et al. Molecular evolution of SARS-CoV-2 from December 2019 to August 2022. J Med Virol 2023; 95: e28366
    Google Scholar
  • 48 Smallman-Raynor MR, Cliff AD. Spatial growth rate of emerging SARS-CoV-2 lineages in England, September 2020-December 2021. Epidemiol Infect 2022; 150: e145
    Google Scholar
  • 49 Meng B, Abdullahi A, Ferreira I. et al. Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity. Nature 2022; 603: 706-714
    Google Scholar
  • 50 Shuai H, Chan JF, Hu B. et al. Attenuated replication and pathogenicity of SARS-CoV-2 B.1.1.529 Omicron. Nature 2022; 603: 693-699
    Google Scholar
  • 51 Suzuki R, Yamasoba D, Kimura I. et al. Attenuated fusogenicity and pathogenicity of SARS-CoV-2 Omicron variant. Nature 2022; 603: 700-705
    Google Scholar
  • 52 Wang Q, Anang S, Iketani S. et al. Functional properties of the spike glycoprotein of the emerging SARS-CoV-2 variant B.1.1.529. Cell Rep 2022; 39: 110924
    Google Scholar
  • 53 Willett BJ, Grove J, MacLean OA. et al. SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway. Nat Microbiol 2022; 7: 1161-1179
    Google Scholar
  • 54 Zhao H, Lu L, Peng Z. et al. SARS-CoV-2 Omicron variant shows less efficient replication and fusion activity when compared with delta variant in TMPRSS2-expressed cells. Emerg Microbes Infect 2022; 11: 277-283
    Google Scholar
  • 55 Nagasawa R, Niwa T, Hagiwara E. et al. Safety and efficacy of combination therapy of remdesivir, baricitinib, and high-dose steroids in patients hospitalized with moderate to severe COVID-19. Intern Med 2023; DOI: 10.2169/internalmedicine.0761-22.
    Google Scholar