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Table of Contents
LETTER TO EDITOR
Year : 2021  |  Volume : 5  |  Issue : 4  |  Page : 76-77

Evaluation of the role of itraconazole and posaconazole in viral infection as immunomodulatory drugs


Department of Microbiology, Al-Shomali General Hospital, Babil, Iraq

Date of Submission25-Jul-2020
Date of Decision15-Aug-2020
Date of Acceptance17-Aug-2020
Date of Web Publication14-Nov-2021

Correspondence Address:
Dr. Falah Hasan Obayes Al-Khikani
Department of Microbiology, Al-Shomali General Hospital, Babil
Iraq
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/MTSM.MTSM_34_20

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How to cite this article:
Obayes Al-Khikani FH. Evaluation of the role of itraconazole and posaconazole in viral infection as immunomodulatory drugs. Matrix Sci Med 2021;5:76-7

How to cite this URL:
Obayes Al-Khikani FH. Evaluation of the role of itraconazole and posaconazole in viral infection as immunomodulatory drugs. Matrix Sci Med [serial online] 2021 [cited 2021 Dec 8];5:76-7. Available from: https://www.matrixscimed.org/text.asp?2021/5/4/76/330437



The widespread therapeutic use of azole-based pharmaceutical drugs has given rise to multiple interests, and their research and development has become a very fast creation of a successful spotlight of infinite space.[1],[2] Itraconazole (ITZ) and posaconazole (POS) belong to triazole that have a broad-spectrum antifungal agent. They commonly used to prevent and treat several fungal infections that cause superfiial, subcutaneous, and systemic infections.[3] These drugs have few side effects compared with other drugs.[4],[5],[6]

Since antifungal drugs are commonly used in patients who are to some extent immunocompromised, it is important to assess the potential effects of these therapies on the immune system.[7],[8],[9] It has been proposed that the efficacy of some antifungal agents may be related to their capacity to induce cytokine production. This also confirmed that some antifungal drugs increase chemokine levels in the supernatants of human mononuclear cell cultures such as CCL3 and CCL4.[10]

From invasive fungal infection that treated with POS are chromoblastomycosis, mucormycosis, candidiasis, fusariosis, mycetoma, cryptococcosis, aspergillosis, and coccidioidomycosis. Furthermore, ITZ drug has a broad range activity on fungal infections in humans, with rare resistance compared with other antibiotics.[11],[12],[13],[14],[15] Besides the antifungal role of POS and ITZ, they have antiviral efficacy against some viruses by different mechanisms of actions.[16]

As shown by both in vitro and in vivo studies, some drugs, especially antibiotics, have direct modulating effects on the immune system, in addition to their antimicrobial acts such as certain antifungal on the activities of animal and human macrophages, monocytes, and neutrophils.[17]

It is also found that ITZ can exert a marked immunomodulatory effect at a serum level of 1 μg/mL (therapeutically achievable concentration), followed by a slight pulmonary immunosuppressive tendency in healthy male BALB/c mice, which suggests an alternative, but unexplored, mechanism of ITZ-mediated immunomodulation.[18]

This lipophilic antifungal drug of POS is absorbed within human cell membranes, including neutrophils and other leukocytes.[19] It concentrates inside dHL-60 cells to high levels.[20] After touch, these cells are capable of transferring POS to Aspergillus fumigatus hyphae and exhibit well antifungal activity to A. fumigatus in vitro.

In an invasive pulmonary aspergillosis neutropenic mouse model, treatment with POS-charged dHL-60 cells resulted in decreased pulmonary fungal burden and even removal of some mice infections. These findings indicate that neutrophils could be an effective mechanism for POS delivery.[21]

A combination of antiviral drugs also has a role in the inhibition of replication of certain viruses such as dengue virus, flvivirus, and Zika virus by reducing the viral single strand RNA replication.[22]

Regarding enteroviruses (which are nonenveloped icosahedral RNA viruses), ITZ identified as an effective inhibitor of EV71 replication in the low micromolar range and also inhibited other enteroviruses including coxsackievirus B3, coxsackievirus A16, enterovirus 68, and poliovirus 1. The mechanism of action by targeting a step involved in RNA replication or polyprotein processing. ITZ and POS may target a specific site(s) in the viral genome.[23]

There are different concentrations of POS found in the plasma. The intracellular absorption of the azoles tends to be passive and dependents on the composition of the extracellular media. Therefore, the intracellular and, consequently, the extracellular concentrations would automatically adjust upon reaching multiple body compartments with distinct extracellular media compositions. The intracellular concentration of POS in mononuclear peripheral blood cells and polymorphonuclear neutrophils has been shown to have greatly increased compared to the plasma concentration.[24] High intracellular POS loading may assist the competent phagocytes in their pathogen killing tasks.[25] ITZ and POS may be promised antiviral therapy to treat some viral infections including those that have no antiviral drugs yet.[26],[27],[28]

In conclusion, from previous studies, ITZ and POS could be an effective drug against many RNA viral infections in multiple mechanisms, including inhibitions of NAADP-stimulated lysosomal calcium release, NPC1 protein function, increase cholesterol level, acidic PH, and stimulating interferon. Because viral infections are common in the world, which is difficult to control, especially RNA viruses with constantly changing, so some studies have conducted a series of experiments on some of the treatments available for reuse to treatment or prevention of viruses.

As it is known, in viral infection immune system plays a crucial role in viral elimination and body defending, so using an antibiotic that has the ability to enhance immune response, activate innate immunity, and stimulate pro-inflammatory responses such as ITZ and POS may be very important to protect from viral invasion. It has strong immunomodulatory characteristics by triggering pro-inflammatory responses; this effect has been associated with protective effects. ITZ and POS act during infection not only on the pathogen but also on the host. This issue is of particular interest because patients affected by viral infections may be immunocompromised.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Zhang HZ, Gan LL, Wang H, Zhou CH. New progress in azole compounds as antimicrobial agents. Mini Rev Med Chem 2017;17:122-66.  Back to cited text no. 1
    
2.
AL-Khikani FH. Dermatophytosis a worldwide contiguous fungal infection: Growing challenge and few solutions. Biomed Biotechnol Res J 2020;4:44.  Back to cited text no. 2
  [Full text]  
3.
Ami RB, Lewis RE, Kontoyiannis DP. Immunopharmacology of modern antifungals. Clin Infect Dis 2008;47:226-35.  Back to cited text no. 3
    
4.
AL-Khikani FH, AL-Janabi AA. Topical amphotericin B formulas: Promising new application. Int J Med Sci Curr Res 2019;2:187-96.  Back to cited text no. 4
    
5.
AL-Khikani FH. Pulmonary mycoses treated by topical amphotericin B. Biomedical and Biotechnology Research Journal (BBRJ) 2020;4:123.  Back to cited text no. 5
    
6.
AL-Khikani FH. Refractory Fungal Vaginitis Treated by Topical Amphotericin B. Review. Medical Science of Ukraine (MSU) 2020;16:55-8.  Back to cited text no. 6
    
7.
Steel HC, Tintinger GR, Anderson R. Comparison of the anti-inflammatory activities of imidazole antimycotics in relation to molecular structure. Chem Biol Drug Design 2008;72:225-8.  Back to cited text no. 7
    
8.
Al-Khikani FH. Amphotericin B as antiviral drug: Possible efficacy against COVID-19. Annals of Thoracic Medicine. 2020;15:118.  Back to cited text no. 8
    
9.
Almosawey HA, AL-Khikani FH, Hameed RM, Abdullah YJ, Al-Ibraheemi MK, Al-Asadi AA. Tamoxifen from chemotherapy to antiviral drug: Possible activity against COVID-19. Biomedical and Biotechnology Research Journal (BBRJ) 2020;4:108.  Back to cited text no. 9
    
10.
Fidan I, Yuksel S, Imir T, Kalkanci A, Kustimur S, Ilhan MN. The effects of fluconazole and cytokines on human mononuclear cells. Memorias do Instituto Oswaldo Cruz 2007;102:127-31.  Back to cited text no. 10
    
11.
AL-Khikani FH. Antimicrobial Resistance Profile Among Major Bacterial Pathog ens in Southern Babil, Iraq. Galician medical journal 2020;27:44.  Back to cited text no. 11
    
12.
AL-Khikani FH, Abadi RM, Ayit AS. Emerging carbapenemase Klebsiella oxytoca with multidrug resistance implicated in urinary tract infection. Biomedical and Biotechnology Research Journal (BBRJ). 2020 ;4:148.  Back to cited text no. 12
    
13.
AL-Khikani FH, Auda Ga, Ayit AS. Correlation study between urinary tract bacterial infection and some acute inflammatory responses. Biomed Biotechnol Res J 2019;3:236-9.  Back to cited text no. 13
  [Full text]  
14.
AL-Khikani FH, Almosawey HS. Be conscious to be healthy: An initiative to prevent recurrent urinary tract infection in Iraqi women. Hamdan Medical Journal. 2020;13:44-5.  Back to cited text no. 14
    
15.
AL-Khikani FH, The forgotten role of methenamine to prevent recurrent urinary tract infection: Urgency for reuse 100 years after discovery. Pharm Biomed Res 2020;6:13-6.  Back to cited text no. 15
    
16.
Al-Khikani FH, Hameed RM. COVID-19 treatment: Possible role of itraconazole as new therapeutic option. Int J Health Allied Sci 2020;9:78.  Back to cited text no. 16
  [Full text]  
17.
Choi JH, Kwon EY, Park CM, Choi SM, Lee DG, Yoo JH, et al. Immunomodulatory effects of antifungal agents on the response of human monocytic cells to Aspergillus fumigatus conidia. Med Mycol 2010;48:704-9.  Back to cited text no. 17
    
18.
Naranjo TW, Lopera D, Zuluaga AF, Cano LE. Immunomodulatory activity of itraconazole in lung. Tropical J Pharm Res 2016;15:2603-9.  Back to cited text no. 18
    
19.
Taccone FS, van den Abeele AM, Bulpa P, Misset B, Meersseman W, Cardoso T, et al. Epidemiology of invasive aspergillosis in critically ill patients: Clinical presentation, underlying conditions, and outcomes. Critical Care 2015;19:7.  Back to cited text no. 19
    
20.
Campoli P, Al Abdallah Q, Robitaille R, Solis NV, Fielhaber JA, Kristof AS, et al. Concentration of antifungal agents within host cell membranes: A new paradigm governing the efficacy of prophylaxis. Antimicrob Agents Chemother 2011;55:5732-9.  Back to cited text no. 20
    
21.
Baistrocchi SR, Lee MJ, Lehoux M, Ralph B, Snarr BD, Robitaille R, et al. Posaconazole-loaded leukocytes as a novel treatment strategy targeting invasive pulmonary aspergillosis. J Infect Dis 2017;215:1734-1.  Back to cited text no. 21
    
22.
Meutiawati F, Bezemer B, Strating JR, Overheul GJ, Žusinaite E, van Kuppeveld FJ, et al. Posaconazole inhibits dengue virus replication by targeting oxysterol-binding protein. Antiviral Res 2018;157:68-79.  Back to cited text no. 22
    
23.
Gao Q, Yuan S, Zhang C, Wang Y, Wang Y, He G, Zou G. Discovery of itraconazole with broad-spectrum In vitro antienterovirus activity that targets nonstructural protein 3A. Antimicrobial Agents Chemother 2015;59:2654-65.  Back to cited text no. 23
    
24.
Minoprio P. Parasite polyclonal activators: New targets for vaccination approaches? Int J Parasitol 2001;31:588-91.  Back to cited text no. 24
    
25.
Farowski F. Quantitation of azoles and echinocandins in compartments of peripheral blood by liquid chromatography-tandem mass spectrometry. Antimicrob Agents Chemother 2010;54:1815-9.  Back to cited text no. 25
    
26.
AL-Khikani FH. Surveillance 2019 novel coronavirus (COVID-19) spreading: Is a terrifying pandemic outbreak is soon? Biomed Biotechnol Res J 2020;4:81-2.  Back to cited text no. 26
    
27.
AL-Khikani FH. The role of blood group in COVID-19 infection: More information is needed. Journal of Nature and Science of Medicine. 2020;3:225.  Back to cited text no. 27
    
28.
Obayes AL-Khikani FH, Kadim BJ, Ayit AS, Abidalali MH. Evaluation Cephalosporins Resistance in Pathogenic Bacteria Isolated Clinically. World News of Natural Sciences. 2020;31:110-9.  Back to cited text no. 28
    




 

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