CC BY 4.0 · Eur J Dent 2022; 16(03): 478-487
DOI: 10.1055/s-0041-1739444
Review Article

Utilizing the Potential of Antimicrobial Peptide LL-37 for Combating SARS-COV- 2 Viral Load in Saliva: an In Silico Analysis

1   Department of Conservative Dentistry and Endodontics, AB Shetty Memorial Institute of Dental Sciences, NITTE (deemed to be) University, Deralakatte, Mangaluru, Karnataka, India
,
2   Central Research Laboratory, K.S. Hegde Medical Academy, NITTE (deemed to be) University, Deralakatte, Mangaluru, Karnataka, India
,
3   Department of Clinical Sciences, Ajman University, Ajman, United Arab Emirates
4   Centre of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates
,
1   Department of Conservative Dentistry and Endodontics, AB Shetty Memorial Institute of Dental Sciences, NITTE (deemed to be) University, Deralakatte, Mangaluru, Karnataka, India
,
5   Department of Biochemistry, K.S. Hegde Medical Academy, NITTE (deemed to be) University, Deralakatte, Mangaluru, Karnataka, India
› Author Affiliations
Funding None.

Abstract

Limiting the spread of virus during the recent pandemic outbreak was a major challenge. Viral loads in saliva, nasopharyngeal and oropharyngeal swabs were the major cause for droplet transmission and aerosols. Saliva being the major contributor for the presence of viral load is the major key factor; various mouthwashes and their combination were analyzed and utilized in health care centers to hamper the spread of virus and decrease viral load. The compositions of these mouthwashes to an extent affected the viral load and thereby transmission, but there is always a scope for other protocols which may provide better results. Here we evaluated the potential of antimicrobial peptide LL-37 in decreasing the viral load of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through an in silico work and evidence from other studies. This narrative review highlighted a brief nonsystematic methodology to include the selected articles for discussion. Accessible electronic databases (Medline, Scopus, Web of Science, SciELO, and PubMed) were used to find studies that reported the salivary viral load of SARS-CoV-2 published between December 2019 and June 2021. The following keywords were utilized for brief searching of the databases: “saliva,” “viral load,” and “SARS-CoV-2.” Articles in English language, in vitro cell-line studies, ex vivo studies, and clinical trials explaining the viral load of SARS-CoV-2 in saliva and strategies to decrease viral load were included in this review. The search was complemented by manual searching of the reference lists of included articles and performing a citation search for any additional reviews. The antiviral potential of cationic host defense peptide LL-37 was evaluated using computational approaches providing in silico evidence. The analysis of docking studies and the display of positive interfacial hydrophobicity of LL-37 resulting in disruption of COVID-19 viral membrane elucidate the fact that LL-37 could be effective against all variants of SARS-CoV-2. Further experimental studies would be needed to confirm the binding of the receptor-binding domain with LL-37. The possibility of using it in many forms further to decrease the viral load by disrupting the viral membrane is seen.

Authors' Contributions

N.N., G.P., and S.R.V.: conceptualization, formal analysis, investigation, resources, validation, writing original draft, review, and editing. M.N.H., and S.K.N.: resources, validation, writing original draft, review, and editing.




Publication History

Article published online:
22 December 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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  • References

  • 1 Xu R, Cui B, Duan X, Zhang P, Zhou X, Yuan Q. Saliva: potential diagnostic value and transmission of 2019-nCoV. Int J Oral Sci 2020; 12 (01) 11
  • 2 Guo YR, Cao QD, Hong ZS. et al. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak - an update on the status. Mil Med Res 2020; 7 (01) 11
  • 3 Liu Q, Luo D, Haase JE. et al. The experiences of health-care providers during the COVID-19 crisis in China: a qualitative study. Lancet Glob Health 2020; 8 (06) e790-e798
  • 4 Diamond G, Beckloff N, Weinberg A, Kisich KO. The roles of antimicrobial peptides in innate host defense. Curr Pharm Des 2009; 15 (21) 2377-2392
  • 5 Pahar B, Madonna S, Das A, Albanesi C, Girolomoni G. Immunomodulatory role of the antimicrobial LL-37 peptide in autoimmune diseases and viral infections. Vaccines (Basel) 2020; 8 (03) 517
  • 6 Ahmed A, Siman-Tov G, Hall G, Bhalla N, Narayanan A. Human antimicrobial peptides as therapeutics for viral infections. Viruses 2019; 11 (08) 704
  • 7 Barlow PG, Findlay EG, Currie SM, Davidson DJ. Antiviral potential of cathelicidins. Future Microbiol 2014; 9 (01) 55-73
  • 8 Mookherjee N, Hancock RE. Cationic host defence peptides: innate immune regulatory peptides as a novel approach for treating infections. Cell Mol Life Sci 2007; 64 (7-8): 922-933
  • 9 Kong R, Yang GB, Xue R. et al. COVID-19 docking server: a meta server for docking small molecules, peptides and antibodies against potential targets of COVID-19. 2020; 36 (20) 5109-5111
  • 10 Tripathi S, Tecle T, Verma A, Crouch E, White M, Hartshorn KL. The human cathelicidin LL-37 inhibits influenza A viruses through a mechanism distinct from that of surfactant protein D or defensins. J Gen Virol 2013; 94 (Pt 1): 40-49
  • 11 Amorim Dos Santos J, Normando AGC, Carvalho da Silva RL. et al. Oral manifestations in patients with COVID-19: a living systematic review. J Dent Res 2021; 100 (02) 141-154
  • 12 Silva J, Lucas C, Sundaram M. et al. Saliva viral load is a dynamic unifying correlate of COVID-19 severity and mortality. medRxiv 2021; DOI: 10.1101/2021.01.04.21249236.
  • 13 Baghizadeh Fini M. Oral saliva and COVID-19. Oral Oncol 2020; 108: 104821
  • 14 Huang N, Pérez P, Kato T. et al; NIH COVID-19 Autopsy Consortium, HCA Oral and Craniofacial Biological Network. SARS-CoV-2 infection of the oral cavity and saliva. Nat Med 2021; 27 (05) 892-903
  • 15 To W-K, Tsang OT, Yip CC. et al. Consistent detection of 2019 novel coronavirus in saliva. Clin Infect Dis 2020; 71 (15) 841-843
  • 16 D'Amico C, Bocchieri S, Stefano R. et al. Dental office prevention of coronavirus infection. Eur J Dent 2020; 14 (S 01): S146-S151
  • 17 Eduardo FP, Corrêa L, Heller D. et al. Salivary SARS-CoV-2 load reduction with mouthwash use: a randomized pilot clinical trial. Heliyon 2021; 7 (06) e07346
  • 18 Seneviratne CJ, Balan P, Ko KKK. et al. Efficacy of commercial mouth-rinses on SARS-CoV-2 viral load in saliva: randomized control trial in Singapore. Infection 2021; 49 (02) 305-311
  • 19 Yoon JG, Yoon J, Song JY. et al. Clinical significance of a high SARS-CoV-2 viral load in the saliva. J Korean Med Sci 2020; 35 (20) e195 doi:10.3346/jkms.2020.35.e195
  • 20 Carrouel F, Valette M, Gadea E. et al. Use of an antiviral mouthwash as a barrier measure in the SARS-CoV-2 transmission in adults with asymptomatic to mild COVID-19: a multicentre, randomized, double-blind controlled trial. Clin Microbiol Infect 2021; 27 (10) 1494-1501
  • 21 Mohebbi Z, Ebrahimi ST, Shamshiri AR. Do mouthwashes reduce Covid-19 viral load during dental procedures and oropharyngeal examinations? A systematic review. Preprints 2021; DOI: 10.20944/preprints202106.0249.v1. still in preprint
  • 22 Komine A, Yamaguchi E, Okamoto N, Yamamoto K. Virucidal activity of oral care products against SARS-CoV-2 in vitro. J Oral Maxillofac Surg Med Pathol 2021; 33 (04) 475-477
  • 23 Stawarz-Janeczek M, Kryczyk-Poprawa A, Muszyńska B, Opoka W, Pytko-Polończyk J. Disinfectants used in stomatology and SARS-CoV-2 infection. Eur J Dent 2021; 15 (02) 388-400
  • 24 Farook FF, Mohamed Nuzaim MN, Taha Ababneh K, Alshammari A, Alkadi L. COVID-19 pandemic: oral health challenges and recommendations. Eur J Dent 2020; 14 (S 01): S165-S170
  • 25 Melo Neto CLM, Bannwart LC, de Melo Moreno AL, Goiato MC. SARS-CoV-2 and dentistry-review. Eur J Dent 2020; 14 (S 01): S130-S139
  • 26 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 (04) e0124706
  • 27 Ahmed A, Siman-Tov G, Keck F. et al. Human cathelicidin peptide LL-37 as a therapeutic antiviral targeting Venezuelan equine encephalitis virus infections. Antiviral Res 2019; 164: 61-69
  • 28 Mansbach JM, Piedra PA, Borregaard N. et al. Serum cathelicidin level is associated with viral etiology and severity of bronchiolitis. J Allergy Clin Immunol 2012; 130 (04) 1007.e1-1008.e1
  • 29 Schögler A, Muster RJ, Kieninger E. et al. Vitamin D represses rhinovirus replication in cystic fibrosis cells by inducing LL-37. Eur Respir J 2016; 47 (02) 520-530
  • 30 Lee CJ, Buznyk O, Kuffova L. et al. Cathelicidin LL-37 and HSV-1 corneal infection: peptide versus gene therapy. Transl Vis Sci Technol 2014; 3 (03) 4
  • 31 He M, Zhang H, Li Y. et al. Cathelicidin-derived antimicrobial peptides inhibit Zika virus through direct inactivation and interferon pathway. Front Immunol 2018; 9: 722
  • 32 Sousa FH, Casanova V, Findlay F. et al. Cathelicidins display conserved direct antiviral activity towards rhinovirus. Peptides 2017; 95: 76-83
  • 33 Yu Y, Cooper CL, Wang G. et al. Engineered human cathelicidin antimicrobial peptides inhibit Ebola virus infection. iScience 2020; 23 (04) 100999
  • 34 Ron-Doitch S, Sawodny B, Kühbacher A. et al. Reduced cytotoxicity and enhanced bioactivity of cationic antimicrobial peptides liposomes in cell cultures and 3D epidermis model against HSV. J Control Release 2016; 229: 163-171
  • 35 Nordström R, Nyström L, Andrén OCJ. et al. Membrane interactions of microgels as carriers of antimicrobial peptides. J Colloid Interface Sci 2018; 513: 141-150
  • 36 Fan R, Tong A, Li X. et al. Enhanced antitumor effects by docetaxel/LL37-loaded thermosensitive hydrogel nanoparticles in peritoneal carcinomatosis of colorectal cancer. Int J Nanomedicine 2015; 10: 7291-7305
  • 37 Fumakia M, Ho EA. Nanoparticles encapsulated with LL37 and serpin A1 promotes wound healing and synergistically enhances antibacterial activity. Mol Pharm 2016; 13 (07) 2318-2331