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Antimicrobial peptides: natural or synthetic defense peptides against HBV and HCV infections

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Abstract

According to the literature, treatment of HCV and HBV infections faces challenges due to problems such as the emergence of drug-resistant mutants, the high cost of treatment, and the side effects of current antiviral therapy. Antimicrobial peptides (AMPs), a group of small peptides, are a part of the immune system and are considered as an alternative treatment for microbial infections. These peptides are water-soluble with amphiphilic (hydrophilic and hydrophobic surfaces) characteristics. AMPs are produced by a wide range of organisms including both prokaryotic and eukaryotic cells. The antiviral mechanisms of AMPs include inhibiting virus entry, inhibiting intracellular virus replication, inhibiting intracellular viral packaging, and inducing immune responses. In addition, AMPs are a new generation of antiviral biomolecules that have very low toxicity for human host cells, particularly liver cell lines. AMPs can be considered as one of the most important strategies for developing new adjuvant drugs in the treatment of HBV and HCV infections. In the present study, several groups of AMPs (with a net positive charge) such as Human cathelicidin, Claudin-1, Defensins, Hepcidin, Lactoferrin, Casein, Plectasin, Micrococcin P1, Scorpion venom, and Synthetic peptides were reviewed with antiviral properties against HBV and HCV.

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References

  1. Cooke GS, Andrieux-Meyer I, Applegate TL, Atun R, Burry JR, Cheinquer H, et al. Accelerating the elimination of viral hepatitis: a Lancet Gastroenterology & Hepatology Commission. lancet Gastroenterol Hepatol. 2019;4(2):135–84.

    Article  PubMed  Google Scholar 

  2. Nelson PK, Mathers BM, Cowie B, Hagan H, Des Jarlais D, Horyniak D, et al. Global epidemiology of hepatitis B and hepatitis C in people who inject drugs: results of systematic reviews. The Lancet. 2011;378(9791):571–83.

    Article  Google Scholar 

  3. Shepard CW, Simard EP, Finelli L, Fiore AE, Bell BP. Hepatitis B virus infection: epidemiology and vaccination. Epidemiol Rev. 2006;28(1):112–25.

    Article  PubMed  Google Scholar 

  4. Alavian SM, Hajarizadeh B, AHMADZADASL M, Kabir A. BAGHERI LK. Hepatitis B Virus infection in Iran: A systematic review. 2008.

  5. Lee WM. Hepatitis B virus infection. N Engl J Med. 1997;337(24):1733–45.

    Article  CAS  PubMed  Google Scholar 

  6. McMahon BJ, editor Epidemiology and natural history of hepatitis B. Seminars in liver disease; 2005: Published in 2005 by Thieme Medical Publishers, Inc., 333 Seventh Avenue &#8230.

  7. Shaw T, Bartholomeusz A, Locarnini S. HBV drug resistance: mechanisms, detection and interpretation. J Hepatol. 2006;44(3):593–606.

    Article  CAS  PubMed  Google Scholar 

  8. Block TM, Gish R, Guo H, Mehta A, Cuconati A, London WT, et al. Chronic hepatitis B: what should be the goal for new therapies? Antiviral Res. 2013;98(1):27–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Gao M, Nettles RE, Belema M, Snyder LB, Nguyen VN, Fridell RA, et al. Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect. Nature. 2010;465(7294):96–100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Tasleem S, Sood GK. Hepatitis C associated B-cell non-Hodgkin lymphoma: clinical features and the role of antiviral therapy. J Clin translational Hepatol. 2015;3(2):134.

    Google Scholar 

  11. Fabrizi F, Dixit V, Messa P. Antiviral therapy of symptomatic HCV-associated mixed cryoglobulinemia: meta‐analysis of clinical studies. J Med Virol. 2013;85(6):1019–27.

    Article  CAS  PubMed  Google Scholar 

  12. Pol S, Vallet-Pichard A, Corouge M, Mallet VO. Hepatitis C. epidemiology, diagnosis, natural history and therapy. Hepatitis C in renal disease. Hemodial transplantation. 2012;176:1–9.

    Google Scholar 

  13. Abdel-Ghaffar TY, Sira MM, El Naghi S. Hepatitis C genotype 4: The past, present, and future. World journal of hepatology. 2015;7(28):2792.

  14. Feld J. J. Direct-acting antivirals for hepatitis C virus (HCV): the progress continues. Curr Drug Targets. 2017;18(7):851–62.

    Article  CAS  PubMed  Google Scholar 

  15. Keikha M, Eslami M, Yousefi B, Ali-Hassanzadeh M, Kamali A, Yousefi M, et al. HCV genotypes and their determinative role in hepatitis C treatment. Virusdisease. 2020:1–6.

  16. Thomas DL. Global control of hepatitis C: where challenge meets opportunity. Nat Med. 2013;19(7):850–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Horner SM, Naggie S. Successes and challenges on the road to cure hepatitis C. PLoS Pathog. 2015;11(6):e1004854.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Kumar D, Farrell GC, Fung C, George J. Hepatitis C virus genotype 3 is cytopathic to hepatocytes: reversal of hepatic steatosis after sustained therapeutic response. Hepatology. 2002;36(5):1266–72.

    Article  PubMed  Google Scholar 

  19. Jenssen H, Hamill P, Hancock RE. Peptide antimicrobial agents. Clin Microbiol Rev. 2006;19(3):491–511.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. da Silva BR, de Freitas VAA, Nascimento-Neto LG, Carneiro VA, Arruda FVS, de Aguiar ASW, et al. Antimicrobial peptide control of pathogenic microorganisms of the oral cavity: a review of the literature. Peptides. 2012;36(2):315–21.

    Article  PubMed  Google Scholar 

  21. Neshani A, Zare H, Akbari Eidgahi MR, Hooshyar Chichaklu A, Movaqar A, Ghazvini K. Review of antimicrobial peptides with anti-Helicobacter pylori activity. Helicobacter. 2019;24(1):e12555.

    Article  PubMed  Google Scholar 

  22. Neshani A, Eidgahi MRA, Zare H, Ghazvini K. Extended-Spectrum antimicrobial activity of the Low cost produced Tilapia Piscidin 4 (TP4) marine antimicrobial peptide. J Res Med Dent Sci. 2018;6(5):327–34.

    Google Scholar 

  23. Mirski T, Niemcewicz M, Bartoszcze M, Gryko R, Michalski A. Utilisation of peptides against microbial infections–a review. Annals of Agricultural and Environmental Medicine. 2018;25(2).

  24. Jahangiri A, Neshani A, Mirhosseini SA, Ghazvini K, Zare H, Sedighian H. Synergistic effect of two antimicrobial peptides, Nisin and P10 with conventional antibiotics against extensively drug-resistant Acinetobacter baumannii and colistin-resistant Pseudomonas aeruginosa isolates. Microb Pathog. 2021;150:104700.

    Article  CAS  PubMed  Google Scholar 

  25. Kosikowska P, Lesner A. Antimicrobial peptides (AMPs) as drug candidates: a patent review (2003–2015). Expert opinion on therapeutic patents. 2016;26(6):689–702.

  26. Kang H-K, Kim C, Seo CH, Park Y. The therapeutic applications of antimicrobial peptides (AMPs): a patent review. J Microbiol. 2017;55(1):1–12.

    Article  CAS  PubMed  Google Scholar 

  27. Tan J, Tay J, Hedrick J, Yang YY. Synthetic macromolecules as therapeutics that overcome resistance in cancer and microbial infection. Biomaterials. 2020;252:120078.

    Article  CAS  PubMed  Google Scholar 

  28. Lei J, Sun L, Huang S, Zhu C, Li P, He J, et al. The antimicrobial peptides and their potential clinical applications. Am J translational Res. 2019;11(7):3919.

    CAS  Google Scholar 

  29. Ahmed A, Siman-Tov G, Hall G, Bhalla N, Narayanan A. Human antimicrobial peptides as therapeutics for viral infections. Viruses. 2019;11(8):704.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Braff MH, Mi‘i AH, Di Nardo A, Lopez-Garcia B, Howell MD, Wong C, et al. Structure-function relationships among human cathelicidin peptides: dissociation of antimicrobial properties from host immunostimulatory activities. J Immunol. 2005;174(7):4271–8.

    Article  CAS  PubMed  Google Scholar 

  31. Neshani A, Zare H, Eidgahi MRA, Kakhki RK, Safdari H, Khaledi A, et al. LL-37: Review of antimicrobial profile against sensitive and antibiotic-resistant human bacterial pathogens. Gene Rep. 2019;17:100519.

    Article  Google Scholar 

  32. Dürr UH, Sudheendra U, Ramamoorthy A. LL-37, the only human member of the cathelicidin family of antimicrobial peptides. Biochim et Biophys Acta (BBA)-Biomembranes. 2006;1758(9):1408–25.

    Article  Google Scholar 

  33. Carretero M, Escámez MJ, García M, Duarte B, Holguín A, Retamosa L, et al. In vitro and in vivo wound healing-promoting activities of human cathelicidin LL-37. J Invest Dermatology. 2008;128(1):223–36.

    Article  CAS  Google Scholar 

  34. Koczulla R, Von Degenfeld G, Kupatt C, Krötz F, Zahler S, Gloe T, et al. An angiogenic role for the human peptide antibiotic LL-37/hCAP-18. J Clin Investig. 2003;111(11):1665–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Chertov O, Michiel DF, Xu L, Wang JM, Tani K, Murphy WJ, et al. Identification of defensin-1, defensin-2, and CAP37/azurocidin as T-cell chemoattractant proteins released from interleukin-8-stimulated neutrophils. J Biol Chem. 1996;271(6):2935–40.

    Article  CAS  PubMed  Google Scholar 

  36. Larrick JW, Hirata M, Balint RF, Lee J, Zhong J, Wright SC. Human CAP18: a novel antimicrobial lipopolysaccharide-binding protein. Infect Immun. 1995;63(4):1291–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. de Miguel Catalina A, Forbrig E, Kozuch J, Nehls C, Paulowski L, Gutsmann T, et al. The C-Terminal VPRTES Tail of LL-37 influences the mode of attachment to a lipid bilayer and antimicrobial activity. Biochemistry. 2019;58(19):2447–62.

    Article  PubMed  Google Scholar 

  38. Zsila F, Kohut G, Beke-Somfai T. Disorder-to-helix conformational conversion of the human immunomodulatory peptide LL-37 induced by antiinflammatory drugs, food dyes and some metabolites. Int J Biol Macromol. 2019;129:50–60.

    Article  CAS  PubMed  Google Scholar 

  39. Iacob SA, Banica D, Panaitescu E, Cojocaru M, Iacob D, editors. The plasma level of cathelicidin-LL37 in patients with chronic hepatitis C virus. Proceedings of World Medical Conference, Malta, ed WSEAS Press; 2010.

  40. Matsumura T, Sugiyama N, Murayama A, Yamada N, Shiina M, Asabe S, et al. Antimicrobial peptide LL-37 attenuates infection of hepatitis C virus. Hepatol Res. 2016;46(9):924–32.

    Article  CAS  PubMed  Google Scholar 

  41. Puig-Basagoiti F, Fukuhara T, Tamura T, Ono C, Uemura K, Kawachi Y, et al. Human cathelicidin compensates for the role of apolipoproteins in hepatitis C virus infectious particle formation. J Virol. 2016;90(19):8464–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Iacob SA, Panaitescu E, Iacob DG, Cojocaru M. The human cathelicidin LL37 peptide has high plasma levels in B and C hepatitis related to viral activity but not to 25-hydroxyvitamin D plasma level. Romanian J Intern Medicine = Revue Roumaine de Med Interne. 2012;50(3):217–23.

    CAS  Google Scholar 

  43. Saleh M, Welsch C, Cai C, Döring C, Gouttenoire J, Friedrich J, et al. Differential modulation of hepatitis C virus replication and innate immune pathways by synthetic calcitriol-analogs. J Steroid Biochem Mol Biol. 2018;183:142–51.

    Article  CAS  PubMed  Google Scholar 

  44. Tsukita S, Furuse M. Occludin and claudins in tight-junction strands: leading or supporting players? Trends Cell Biol. 1999;9(7):268–73.

    Article  CAS  PubMed  Google Scholar 

  45. Dhawan P, Singh AB, Deane NG, No Y, Shiou S-R, Schmidt C, et al. Claudin-1 regulates cellular transformation and metastatic behavior in colon cancer. J Clin Investig. 2005;115(7):1765–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Evans MJ, von Hahn T, Tscherne DM, Syder AJ, Panis M, Wölk B, et al. Claudin-1 is a hepatitis C virus co-receptor required for a late step in entry. Nature. 2007;446(7137):801–5.

    Article  CAS  PubMed  Google Scholar 

  47. Si Y, Liu S, Liu X, Jacobs JL, Cheng M, Niu Y, et al. A human claudin-1–derived peptide inhibits hepatitis C virus entry. Hepatology. 2012;56(2):507–15.

    Article  CAS  PubMed  Google Scholar 

  48. Selsted ME, Ouellette AJ. Mammalian defensins in the antimicrobial immune response. Nat Immunol. 2005;6(6):551–7.

    Article  CAS  PubMed  Google Scholar 

  49. Lehrer RI, Lichtenstein AK, Ganz T. Defensins: antimicrobial and cytotoxic peptides of mammalian cells. Annu Rev Immunol. 1993;11(1):105–28.

    Article  CAS  PubMed  Google Scholar 

  50. Shafee TM, Lay FT, Phan TK, Anderson MA, Hulett MD. Convergent evolution of defensin sequence, structure and function. Cell Mol Life Sci. 2017;74(4):663–82.

    Article  CAS  PubMed  Google Scholar 

  51. Daher KA, Selsted ME, Lehrer RI. Direct inactivation of viruses by human granulocyte defensins. J Virol. 1986;60(3):1068–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Zhang L, Yu W, He T, Yu J, Caffrey RE, Dalmasso EA, et al. Contribution of human α-defensin 1, 2, and 3 to the anti-HIV-1 activity of CD8 antiviral factor. Science. 2002;298(5595):995–1000.

    Article  CAS  PubMed  Google Scholar 

  53. Ryan LK, Dai J, Yin Z, Megjugorac N, Uhlhorn V, Yim S, et al. Modulation of human β-defensin‐1 (hBD‐1) in plasmacytoid dendritic cells (PDC), monocytes, and epithelial cells by influenza virus, Herpes simplex virus, and Sendai virus and its possible role in innate immunity. J Leukoc Biol. 2011;90(2):343–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Ericksen B, Wu Z, Lu W, Lehrer RI. Antibacterial activity and specificity of the six human α-defensins. Antimicrob Agents Chemother. 2005;49(1):269–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Hoffmann JA, Hetru C. Insect defensins: inducible antibacterial peptides. Immunol Today. 1992;13(10):411–5.

    Article  CAS  PubMed  Google Scholar 

  56. Lay F, Anderson M. Defensins-components of the innate immune system in plants. Curr Protein Pept Sci. 2005;6(1):85–101.

    Article  CAS  PubMed  Google Scholar 

  57. Mattar EH, Almehdar HA, AlJaddawi AA, Abu Zeid IEM, Redwan EM. Elevated concentration of defensins in hepatitis C virus-infected patients. Journal of immunology research. 2016;2016.

  58. Owusu DO, Owusu M, Owusu BA. Human defensins and Th-1 cytokines in hepatitis C viral infection. The Pan African Medical Journal. 2020;37.

  59. Aceti A, Mangoni M, Pasquazzi C, Fiocco D, Marangi M, Miele R, et al. α-Defensin increase in peripheral blood mononuclear cells from patients with hepatitis C virus chronic infection. J Viral Hepatitis. 2006;13(12):821–7.

    Article  CAS  Google Scholar 

  60. Kaltsa G, Bamias G, Siakavellas SI, Goukos D, Karagiannakis D, Zampeli E, et al. Systemic levels of human β-defensin 1 are elevated in patients with cirrhosis. Annals of Gastroenterology: Quarterly Publication of the Hellenic Society of Gastroenterology. 2016;29(1):63.

    Google Scholar 

  61. Ling Y-M, Chen J-Y, Guo L, Wang C-Y, Tan W-T, Wen Q, et al. β-defensin 1 expression in HCV infected liver/liver cancer: an important role in protecting HCV progression and liver cancer development. Sci Rep. 2017;7(1):1–14.

    Article  Google Scholar 

  62. Ma D, Lin L, Zhang K, Han Z, Shao Y, Liu X, et al. Three novel Anas platyrhynchos avian β-defensins, upregulated by duck hepatitis virus, with antibacterial and antiviral activities. Mol Immunol. 2011;49(1–2):84–96.

    Article  CAS  PubMed  Google Scholar 

  63. Chen F, Yu M, Zhong Y, Wang L, Huang H. Characteristics and Role of Neutrophil Extracellular Traps in Asthma. Inflammation. 2021:1–8.

  64. Mattar EH, Almehdar HA, Uversky VN, Redwan EM. Virucidal activity of human α-and β-defensins against hepatitis C virus genotype 4. Mol Biosyst. 2016;12(9):2785–97.

    Article  CAS  PubMed  Google Scholar 

  65. Cheng Y, Sun F, Li S, Gao M, Wang L, Sarhan M, et al. Inhibitory activity of a scorpion defensin BmKDfsin3 against Hepatitis C virus. Antibiotics. 2020;9(1):33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Zeng Z, Zhang Q, Hong W, Xie Y, Liu Y, Li W, et al. A scorpion defensin bmkdfsin4 inhibits hepatitis b virus replication in vitro. Toxins. 2016;8(5):124.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Cuesta A, Meseguer J, Esteban MA. The antimicrobial peptide hepcidin exerts an important role in the innate immunity against bacteria in the bony fish gilthead seabream. Mol Immunol. 2008;45(8):2333–42.

    Article  CAS  PubMed  Google Scholar 

  68. Krause A, Neitz S, Mägert H-J, Schulz A, Forssmann W-G, Schulz-Knappe P, et al. LEAP-1, a novel highly disulfide-bonded human peptide, exhibits antimicrobial activity. FEBS Lett. 2000;480(2–3):147–50.

    Article  CAS  PubMed  Google Scholar 

  69. Fujita N, Sugimoto R, Takeo M, Urawa N, Mifuji R, Tanaka H, et al. Hepcidin expression in the liver: relatively low level in patients with chronic hepatitis C. Mol Med. 2007;13(1):97–104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Girelli D, Pasino M, Goodnough JB, Nemeth E, Guido M, Castagna A, et al. Reduced serum hepcidin levels in patients with chronic hepatitis C. J Hepatol. 2009;51(5):845–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Lin D, Ding J, Liu J-Y, He Y-F, Dai Z, Chen C-Z, et al. Decreased serum hepcidin concentration correlates with brain iron deposition in patients with HBV-related cirrhosis. PLoS ONE. 2013;8(6):e65551.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Fontana RJ, Israel J, LeClair P, Banner BF, Tortorelli K, Grace N, et al. Iron reduction before and during interferon therapy of chronic hepatitis C: results of a multicenter, randomized, controlled trial. Hepatology. 2000;31(3):730–6.

    Article  CAS  PubMed  Google Scholar 

  73. Piperno A, Sampietro M, D’Alba R, Roffi L, Fargion S, Parma S, et al. Iron stores, response to α-interferon therapy, and effects of iron depletion in chronic hepatitis C. Liver. 1996;16(4):248–54.

    Article  CAS  PubMed  Google Scholar 

  74. Fargion S, Fracanzani AL, Rossini A, Borzio M, Riggio O, Belloni G, et al. Iron reduction and sustained response to interferon-α therapy in patients with chronic hepatitis C: results of an Italian multicenter randomized study. Am J Gastroenterol. 2002;97(5):1204–10.

    CAS  PubMed  Google Scholar 

  75. Liu H, Le Trinh T, Dong H, Keith R, Nelson D, Liu C. Iron regulator hepcidin exhibits antiviral activity against hepatitis C virus. PLoS ONE. 2012;7(10):e46631.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Kohjima M, Yoshimoto T, Enjoji M, Fukushima N, Fukuizumi K, Nakamura T, et al. Hepcidin/ferroportin expression levels involve efficacy of pegylated-interferon plus ribavirin in hepatitis C virus-infected liver. World J Gastroenterology: WJG. 2015;21(11):3291.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Inomata S, Anan A, Yamauchi E, Yamauchi R, Kunimoto H, Takata K, et al. Changes in the serum hepcidin-to-ferritin ratio with erythroferrone after hepatitis C virus eradication using direct-acting antiviral agents. Intern Med. 2019;58(20):2915–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Hörl WH, Schmidt A. Low hepcidin triggers hepatic iron accumulation in patients with hepatitis C. Nephrol Dialysis Transplantation. 2014;29(6):1141–4.

    Article  Google Scholar 

  79. Bartolomei G, Cevik RE, Marcello A. Modulation of hepatitis C virus replication by iron and hepcidin in Huh7 hepatocytes. J Gen Virol. 2011;92(9):2072–81.

    Article  CAS  PubMed  Google Scholar 

  80. Olmez OF, Gurel S, Yilmaz Y. Plasma prohepcidin levels in patients with chronic viral hepatitis: relationship with liver fibrosis. Eur J Gastroenterol Hepatol. 2010;22(4):461–5.

    Article  CAS  PubMed  Google Scholar 

  81. Georgopoulou U, Dimitriadis A, Foka P, Karamichali E, Mamalaki A. Hepcidin and the iron enigma in HCV infection. Virulence. 2014;5(4):465–76.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Kemna EH, Tjalsma H, Willems J, Swinkels DW. Hepcidin: from discovery to differential diagnosis. 2008.

  83. Wang X-h, Cheng P-P, Jiang F, Jiao X-Y. The effect of hepatitis B virus infection on hepcidin expression in hepatitis B patients. Annals of Clinical & Laboratory Science. 2013;43(2):126–34.

    CAS  Google Scholar 

  84. Orsi N. The antimicrobial activity of lactoferrin: current status and perspectives. Biometals. 2004;17(3):189–96.

    Article  CAS  PubMed  Google Scholar 

  85. Valenti P, Antonini G. Lactoferrin. Cell Mol Life Sci. 2005;62(22):2576–87.

    Article  CAS  PubMed  Google Scholar 

  86. Hara K, Ikeda M, Saito S, Matsumoto S, Numata K, Kato N, et al. Lactoferrin inhibits hepatitis B virus infection in cultured human hepatocytes. Hepatol Res. 2002;24(3):228–35.

    Article  CAS  PubMed  Google Scholar 

  87. Redwan EM, El-Fakharany EM, Uversky VN, Linjawi MH. Screening the anti infectivity potentials of native N-and C-lobes derived from the camel lactoferrin against hepatitis C virus. BMC Complement Altern Med. 2014;14(1):1–16.

    Article  Google Scholar 

  88. Jenssen H. Anti herpes simplex virus activity of lactoferrin/lactoferricin–an example of antiviral activity of antimicrobial protein/peptide. Cell Mol Life Sci CMLS. 2005;62(24):3002–13.

    Article  CAS  PubMed  Google Scholar 

  89. HASEGAWA K, MOTSUCHI W, TANAKA S. DOSAKO S-i. Inhibition with lactoferrin of in vitro infection with human herpes virus. Jpn J Med Sci Biol. 1994;47(2):73–85.

    Article  CAS  PubMed  Google Scholar 

  90. Berkhout B, van Wamel JL, Beljaars L, Meijer DK, Visser S, Floris R. Characterization of the anti-HIV effects of native lactoferrin and other milk proteins and protein-derived peptides. Antiviral Res. 2002;55(2):341–55.

    Article  CAS  PubMed  Google Scholar 

  91. Baker E, Baker H. Lactoferrin. Cell Mol Life Sci. 2005;62(22):2531–9.

    Article  CAS  PubMed  Google Scholar 

  92. Berlutti F, Pantanella F, Natalizi T, Frioni A, Paesano R, Polimeni A, et al. Antiviral properties of lactoferrin—a natural immunity molecule. Molecules. 2011;16(8):6992–7018.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Florian PE, Macovei A, Lazar C, Milac AL, Sokolowska I, Darie CC, et al. Characterization of the anti-HBV activity of HLP1–23, a human lactoferrin‐derived peptide. J Med Virol. 2013;85(5):780–8.

    Article  CAS  PubMed  Google Scholar 

  94. Yi M, Kaneko S, Yu D, Murakami S. Hepatitis C virus envelope proteins bind lactoferrin. J Virol. 1997;71(8):5997–6002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Picard-Jean F, Bouchard S, Larivée G, Bisaillon M. The intracellular inhibition of HCV replication represents a novel mechanism of action by the innate immune Lactoferrin protein. Antiviral Res. 2014;111:13–22.

    Article  CAS  PubMed  Google Scholar 

  96. El-Fakharany EM, Serour EA, Abdelrahman AM, Haroun BM, Redwan E-RM. Purification and characterization of camel (Camelus dromedarius) milk amylase. Prep Biochem Biotechnol. 2009;39(2):105–23.

    Article  CAS  PubMed  Google Scholar 

  97. Almahdy O, El-Fakharany EM, Ehab E-D, Ng TB, Redwan EM. Examination of the activity of camel milk casein against hepatitis C virus (genotype-4a) and its apoptotic potential in hepatoma and hela cell lines. Hepat monthly. 2011;11(9):724.

    Article  Google Scholar 

  98. Redwan ERM, Tabll A. Camel lactoferrin markedly inhibits hepatitis C virus genotype 4 infection of human peripheral blood leukocytes. J Immunoassay Immunochem. 2007;28(3):267–77.

    Article  CAS  PubMed  Google Scholar 

  99. EL FAKHARANY EM, Tabll A, Abd El Wahab A, Haroun BM, Redwan E-RM. Potential activity of camel milk-amylase and lactoferrin against hepatitis C virus infectivity in HepG2 and lymphocytes. 2008.

  100. Mygind PH, Fischer RL, Schnorr KM, Hansen MT, Sönksen CP, Ludvigsen S, et al. Plectasin is a peptide antibiotic with therapeutic potential from a saprophytic fungus. Nature. 2005;437(7061):975–80.

    Article  CAS  PubMed  Google Scholar 

  101. Greber E, Dawgul K. M. Antimicrobial peptides under clinical trials. Curr Top Med Chem. 2017;17(5):620–8.

    Article  CAS  PubMed  Google Scholar 

  102. Abdulrahman AY, Rothan HA, Rashid NN, Lim SK, Sakhor W, Tee KC, et al. Identification of peptide leads to inhibit hepatitis C virus: inhibitory effect of plectasin peptide against hepatitis C serine protease. Int J Pept Res Ther. 2017;23(2):163–70.

    Article  CAS  Google Scholar 

  103. Lim SK, Othman R, Yusof R, Heh CH. Rational drug discovery: Ellagic acid as a potent dual-target inhibitor against hepatitis C virus genotype 3 (HCV G3) NS3 enzymes. Chem Biol Drug Des. 2021;97(1):28–40.

    Article  CAS  PubMed  Google Scholar 

  104. Ciufolini MA, Lefranc D. Micrococcin P1: structure, biology and synthesis. Nat Prod Rep. 2010;27(3):330–42.

    Article  CAS  PubMed  Google Scholar 

  105. Carnio MC, Stachelhaus T, Francis KP, Scherer S. Pyridinyl polythiazole class peptide antibiotic micrococcin P1, secreted by foodborne Staphylococcus equorum WS2733, is biosynthesized nonribosomally. Eur J Biochem. 2001;268(24):6390–401.

    Article  CAS  PubMed  Google Scholar 

  106. Rogers MJ, Cundliffe E, McCutchan TF. The antibiotic micrococcin is a potent inhibitor of growth and protein synthesis in the malaria parasite. Antimicrob Agents Chemother. 1998;42(3):715–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Ciufolini MA, Shen Y-C. Synthesis of the Bycroft – Gowland Structure of Micrococcin P1. Org Lett. 1999;1(11):1843–6.

    Article  CAS  PubMed  Google Scholar 

  108. Lee M, Yang J, Park S, Jo E, Kim H-Y, Bae Y-S, et al. Micrococcin P1, a naturally occurring macrocyclic peptide inhibiting hepatitis C virus entry in a pan-genotypic manner. Antiviral Res. 2016;132:287–95.

    Article  CAS  PubMed  Google Scholar 

  109. Dai C, Ma Y, Zhao Z, Zhao R, Wang Q, Wu Y, et al. Mucroporin, the first cationic host defense peptide from the venom of Lychas mucronatus. Antimicrob Agents Chemother. 2008;52(11):3967–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Harrison PL, Abdel-Rahman MA, Miller K, Strong PN. Antimicrobial peptides from scorpion venoms. Toxicon. 2014;88:115–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. El-Bitar AM, Sarhan MM, Aoki C, Takahara Y, Komoto M, Deng L, et al. Virocidal activity of Egyptian scorpion venoms against hepatitis C virus. Virol J. 2015;12(1):1–9.

    Article  CAS  Google Scholar 

  112. Yan R, Zhao Z, He Y, Wu L, Cai D, Hong W, et al. A new natural α-helical peptide from the venom of the scorpion Heterometrus petersii kills HCV. Peptides. 2011;32(1):11–9.

    Article  CAS  PubMed  Google Scholar 

  113. Hong W, Zhang R, Di Z, He Y, Zhao Z, Hu J, et al. Design of histidine-rich peptides with enhanced bioavailability and inhibitory activity against hepatitis C virus. Biomaterials. 2013;34(13):3511–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. El Hidan MA, Laaradia MA, El Hiba O, Draoui A, Aimrane A, Kahime K. Scorpion-Derived Antiviral Peptides with a Special Focus on Medically Important Viruses: An Update. BioMed Research International. 2021;2021.

  115. Zeng Z, Zhang R, Hong W, Cheng Y, Wang H, Lang Y, et al. Histidine-rich modification of a scorpion-derived peptide improves bioavailability and inhibitory activity against HSV-1. Theranostics. 2018;8(1):199.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Zhao Z, Hong W, Zeng Z, Wu Y, Hu K, Tian X, et al. Mucroporin-M1 inhibits hepatitis B virus replication by activating the mitogen-activated protein kinase (MAPK) pathway and down-regulating HNF4α in vitro and in vivo. J Biol Chem. 2012;287(36):30181–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Pandey R, Singh A, Pandey A, Tripathi P, Majumdar S, Nath L. Protein and peptide drugs: a brief review. Res J Pharm Technol. 2009;2(2):228–33.

    Google Scholar 

  118. Katsila T, Siskos AP, Tamvakopoulos C. Peptide and protein drugs: the study of their metabolism and catabolism by mass spectrometry. Mass Spectrom Rev. 2012;31(1):110–33.

    Article  CAS  PubMed  Google Scholar 

  119. Bidwell GL. Peptides for cancer therapy: a drug-development opportunity and a drug-delivery challenge. Therapeutic delivery. 2012;3(5):609–21.

    Article  CAS  PubMed  Google Scholar 

  120. Albericio F, Kruger HG. Therapeutic peptides. Future Med Chem. 2012;4(12):1527–31.

    Article  CAS  PubMed  Google Scholar 

  121. Dombu CY, Betbeder D. Airway delivery of peptides and proteins using nanoparticles. Biomaterials. 2013;34(2):516–25.

    Article  CAS  PubMed  Google Scholar 

  122. Cheng G, Montero A, Gastaminza P, Whitten-Bauer C, Wieland SF, Isogawa M, et al. A virocidal amphipathic α-helical peptide that inhibits hepatitis C virus infection in vitro. Proceedings of the National Academy of Sciences. 2008;105(8):3088-93.

  123. Eron JJ, Gulick RM, Bartlett JA, Merigan T, Arduino R, Kilby JM, et al. Short-term safety and antiretroviral activity of T-1249, a second-generation fusion inhibitor of HIV. J Infect Dis. 2004;189(6):1075–83.

    Article  CAS  PubMed  Google Scholar 

  124. Martins do Canto AMT, Palace Carvalho A, Prates Ramalho J, Loura L. Molecular dynamics simulation of HIV fusion inhibitor T-1249: insights on peptide-lipid interaction. Computational and mathematical methods in medicine. 2012;2012.

  125. Montero A, Gastaminza P, Law M, Cheng G, Chisari FV, Ghadiri MR. Self-assembling peptide nanotubes with antiviral activity against hepatitis C virus. Chem Biol. 2011;18(11):1453–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Bruss V, Ganem D. The role of envelope proteins in hepatitis B virus assembly. Proceedings of the National Academy of Sciences. 1991;88(3):1059-63.

  127. Le Seyec J, Chouteau P, Cannie I, Guguen-Guillouzo C, Gripon P. Role of the pre-S2 domain of the large envelope protein in hepatitis B virus assembly and infectivity. J Virol. 1998;72(7):5573–8.

    Article  PubMed  PubMed Central  Google Scholar 

  128. Le Seyec J, Chouteau P, Cannie I, Guguen-Guillouzo C, Gripon P. Infection process of the hepatitis B virus depends on the presence of a defined sequence in the pre-S1 domain. J Virol. 1999;73(3):2052–7.

    Article  PubMed  PubMed Central  Google Scholar 

  129. Gripon P, Cannie I, Urban S. Efficient inhibition of hepatitis B virus infection by acylated peptides derived from the large viral surface protein. J Virol. 2005;79(3):1613–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Deng Q, Zhai J-w, Michel M-L, Zhang J, Qin J, Kong Y-y, et al. Identification and characterization of peptides that interact with hepatitis B virus via the putative receptor binding site. J Virol. 2007;81(8):4244–54.

    Article  CAS  PubMed  Google Scholar 

  131. Glebe D, Aliakbari M, Krass P, Knoop EV, Valerius KP, Gerlich WH. Pre-s1 antigen-dependent infection of Tupaia hepatocyte cultures with human hepatitis B virus. J Virol. 2003;77(17):9511–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Smith JG, Nemerow GR. Mechanism of adenovirus neutralization by human α-defensins. Cell Host Microbe. 2008;3(1):11–9.

    Article  CAS  PubMed  Google Scholar 

  133. Smith JG, Silvestry M, Lindert S, Lu W, Nemerow GR, Stewart PL. Insight into the mechanisms of adenovirus capsid disassembly from studies of defensin neutralization. PLoS Pathog. 2010;6(6):e1000959.

    Article  PubMed  PubMed Central  Google Scholar 

  134. Hsieh I-N, Hartshorn KL. The role of antimicrobial peptides in influenza virus infection and their potential as antiviral and immunomodulatory therapy. Pharmaceuticals. 2016;9(3):53.

    Article  PubMed  PubMed Central  Google Scholar 

  135. Tripathi S, Wang G, White M, Qi L, Taubenberger J, Hartshorn KL. Antiviral activity of the human cathelicidin, LL-37, and derived peptides on seasonal and pandemic influenza A viruses. PLoS ONE. 2015;10(4):e0124706.

    Article  PubMed  PubMed Central  Google Scholar 

  136. Pace BT, Lackner AA, Porter E, Pahar B. The role of defensins in HIV pathogenesis. Mediators of inflammation. 2017;2017.

  137. Hazrati E, Galen B, Lu W, Wang W, Ouyang Y, Keller MJ, et al. Human α-and β-defensins block multiple steps in herpes simplex virus infection. J Immunol. 2006;177(12):8658–66.

    Article  CAS  PubMed  Google Scholar 

  138. Kota S, Sabbah A, Harnack R, Xiang Y, Meng X, Bose S. Role of human β-defensin-2 during tumor necrosis factor-α/NF-κB-mediated innate antiviral response against human respiratory syncytial virus. J Biol Chem. 2008;283(33):22417–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Alagarasu K, Patil P, Shil P, Seervi M, Kakade M, Tillu H, et al. In-vitro effect of human cathelicidin antimicrobial peptide LL-37 on dengue virus type 2. Peptides. 2017;92:23–30.

    Article  CAS  PubMed  Google Scholar 

  140. Buck CB, Day PM, Thompson CD, Lubkowski J, Lu W, Lowy DR, et al. Human α-defensins block papillomavirus infection. Proceedings of the National Academy of Sciences. 2006;103(5):1516-21.

  141. Marr AK, Gooderham WJ, Hancock RE. Antibacterial peptides for therapeutic use: obstacles and realistic outlook. Curr Opin Pharmacol. 2006;6(5):468–72.

    Article  CAS  PubMed  Google Scholar 

  142. Costa F, Carvalho IF, Montelaro RC, Gomes P, Martins MCL. Covalent immobilization of antimicrobial peptides (AMPs) onto biomaterial surfaces. Acta Biomater. 2011;7(4):1431–40.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We appreciate from both Mashhad University of Medical Sciences and Jiroft University of Medical Sciences.

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Authors and Affiliations

  1. Department of Microbiology and Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Masoud Keikha & Kiarash Ghazvini

  2. Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Masoud Keikha & Kiarash Ghazvini

  3. Department of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Hossein Kamali

  4. Department of Microbiology and Virology, School of Medicine, Jiroft University of Medical Sciences, Jiroft, Iran

    Mohsen Karbalaei

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  1. Masoud Keikha
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1. MK1 has contributed to design of the work and analysis of data. 2. HK has contributed to design of the work. 3. KGH has contributed to design of the work. 4. MK2 has drafted the work and substantively revised it. All authors read and approved the final manuscript.

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Keikha, M., Kamali, H., Ghazvini, K. et al. Antimicrobial peptides: natural or synthetic defense peptides against HBV and HCV infections. VirusDis. 33, 445–455 (2022). https://doi.org/10.1007/s13337-022-00790-y

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