COVID-19. Chitosan as prevention. Can it work? Introduction There is a question that should be answered today: while waiting for an approved vaccine, is it possible to contain the spread of the COVI ...

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COVID-19. Chitosan as prevention. Can it work?

Introduction

There is a question that should be answered today: while waiting for an approved vaccine, is it possible to contain the spread of the COVID-19 epidemic with a low toxicity drug that inhibits the virus/receptor ratio so as to prevent its entry?

Discussion

Coronaviruses usually cause only colds in healthy individuals and in the initial phase, while in the subsequent phase, the disease can lead to pneumonia with serious consequences in adults above the age of 60 and/or immunodepressed.  Influenza epidemics explode every year between autumn and winter and, worldwide, infect about 3/5 million people with 250/500,000 deaths (1-2).

 Let us now consider the typology in percentage of people affected by the virus: about 80% over 40 years old while the percentage is drastically reduced to 5.3% between 0 and 20 years old (3).  The mortality rate was 2.8% for men and 1.7% for women while the highest mortality rate was 14.8% in the 80-year-old age group. Influences predominantly affect males, both in the older population and in the younger population (4) with a male-to-woman ratio of 1.3 in Europe and women develop a higher innate and adaptive immune response, which can be beneficial when encountering pathogens (5). These data confirm that the virus can enter more easily and cause more damage in those age groups where the immune system is less protected.

Now, since immunodepression is the facilitated way for the virus to create damage, a viable route could be to block the entry of the virus by first strengthening the immune system with natural antibacterial products and using a broad spectrum inhibitor to block the interactivity relationship between the virus and the human ACE2 receptor, a zincopeptidase membrane converted by angiotensin which is found distributed in the human body and more concentrated in kidney, testicles, heart. In particular, this blocking attempt must be made before the virus has entered our system as it may be contraindicated if the virus is already present (6).

It has been shown that the expression of ADA2 and several Ada2-mediated cell wall related genes (ALS2, PGA45, and ACE2) and efflux transporter genes (MDR1 and CDR1) have been significantly inhibited by chitosan (7) and the action of chitosan has been widely described by recent studies (8), so let us examine the likely benefits of this component.

Chitosan is a naturally abundant polysaccharide and has demonstrated excellent biocompatibility, biodegradability, mechanical strength and low toxicity.

It is obtained by alkaline N-deacetylation of chitin, which is the main component of the exoskeleton of crustaceans, such as shrimps, crabs and lobsters (9).

Many studies have focused on its function as a vector, in regenerative medicine, of bioactive molecules (10), of bone tissue regenerator (11), of its potential for tissue engineering on articular cartilage (12).

In vivo experiments showed that unmodified Chitosan nanoparticles were able to reverse fibrosis with a 100% survival rate at the end of the study, indicating the ability of Chitosan nanoparticles to provide functional collagenase to the fibrotic liver and making the use of collagen binding peptides unnecessary (13).

Because of its low toxicity and biodegradability properties, Chitosan has been used as an antimicrobial agent (14).

Chitosan and cationically modified chitosan (HTCC) are biomaterials that can be used to improve immune efficacy and improve immune response due to their promising mucoadhesive properties (15).

Conclusion

The combined action of a robust strengthening of immune defences combined with the intake of chitosan could be a preventive way of protection against COVID-19.

References__________________________________________________________________

(1) Gabriel G, Arck PC. Sex, immunity and influenza. J Infect Dis. 2014;209 Suppl 3:S93–S99. doi:10.1093/infdis/jiu020

(2) Iuliano AD, Roguski KM, Chang HH, Muscatello DJ, Palekar R, Tempia S, Cohen C, Gran JM, Schanzer D, Cowling BJ, Wu P, Kyncl J, Ang LW, Park M, Redlberger-Fritz M, Yu H, Espenhain L, Krishnan A, Emukule G, van Asten L, Pereira da Silva S, Aungkulanon S, Buchholz U, Widdowson MA, Bresee JS; Global Seasonal Influenza-associated Mortality Collaborator Network.  Estimates of global seasonal influenza-associated respiratory mortality: a modelling study.  Lancet. 2018 Mar 31;391(10127):1285-1300. doi: 10.1016/S0140-6736(17)33293-2

(3) Novel Coronavirus Pneumonia Emergency Response Epidemiology Team. Zhonghua Liu Xing Bing Xue Za Zhi. 2020;41(2):145–151. doi:10.3760/cma.j.issn.0254-6450.2020.02.003

(4) Jensen-Fangel S, Mohey R, Johnsen SP, Andersen PL, S'rensen HT, Ostergaard L. Gender Differences in Hospitalization Rates for Respiratory Tract Infections in Danish Youth Scand J infect Dis. 2004;36(1):31-6.

(5) Gabriel G, Arck PC. Sex, immunity and influenza. J Infect Dis. 2014;209 Suppl 3:S93–S99. doi:10.1093/infdis/jiu020

(6) Diaz JH. Hypothesis: angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may increase the risk of severe COVID-19 [published online ahead of print, 2020 Mar 18]. J Travel Med. 2020;taaa041. doi:10.1093/jtm/taaa041

(7) Shih PY, Liao YT, Tseng YK, Deng FS, Lin CH. A Potential Antifungal Effect of Chitosan Against Candida albicans Is Mediated via the Inhibition of SAGA Complex Component Expression and the Subsequent Alteration of Cell Surface Integrity. Front Microbiol. 2019;10:602. Published 2019 Mar 26. doi:10.3389/fmicb.2019.00602

(8) Foureaux G, Franca JR, Nogueira JC, et al. Ocular Inserts for Sustained Release of the Angiotensin-Converting Enzyme 2 Activator, Diminazene Aceturate, to Treat Glaucoma in Rats. PLoS One. 2015;10(7):e0133149. Published 2015 Jul 23. doi:10.1371/journal.pone.0133149

(9) Roberto Nisticò Aquatic-Derived Biomaterials for a Sustainable Future: A European Opportunity.  Resources 2017, 6(4), 65; https://doi.org/10.3390/resources6040065

 (10 ) Cheung RC, Ng TB, Wong JH, Chan WY. Chitosan: An Update on Potential Biomedical and Pharmaceutical Applications. Mar Drugs. 2015 Aug 14;13(8):5156-86. doi: 10.3390/md13085156.

(11) Mi L, Liu H, Gao Y, Miao H, Ruan J.  Injectable nanoparticles/hydrogels composite as sustained release system with stromal cell-derived factor-1α for calvarial bone regeneration.  Int J Biol Macromol. 2017 Aug;101:341-347. doi: 10.1016/j.ijbiomac.2017.03.098.

(12) Suh JK, Matthew HW.  Application of chitosan-based polysaccharide biomaterials in cartilage tissue engineering: a review.  Biomaterials. 2000 Dec;21(24):2589-98.

(13) El-Safy S, Tammam SN, Abdel-Halim M, Ali ME, Youshia J, Shetab Boushehri MA, Lamprecht A, Mansour S.  Collagenase loaded chitosan nanoparticles for digestion of the collagenous scar in liver fibrosis: the effect of chitosan intrinsic collagen binding on the success of targeting.  Eur J Pharm Biopharm. 2020 Jan 13. pii: S0939-6411(20)30007-2. doi: 10.1016/j.ejpb.2020.01.003.

(14) Kong M, Chen XG, Xing K, Park HJ. Antimicrobial properties of chitosan and mode of action: a state of the art review.  Int J Food Microbiol. 2010 Nov 15;144(1):51-63. doi: 10.1016/j.ijfoodmicro.2010.09.012.

(15) Zhao J, Li J, Jiang Z, et al. Chitosan, N,N,N-trimethyl chitosan (TMC) and 2-hydroxypropyltrimethyl ammonium chloride chitosan (HTCC): The potential immune adjuvants and nano carriers [published online ahead of print, 2020 Mar 14]. Int J Biol Macromol. 2020;S0141-8130(19)36837-0. doi:10.1016/j.ijbiomac.2020.03.065

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