Inosine Pranobex Deserves Attention as a Potential Immunomodulator to Achieve Early Alteration of the COVID-19 Disease Course

Since its licensing in 1971, the synthetic compound inosine pranobex has been effectively combating viral infections, including herpes zoster, varicella, measles, and infections caused by the herpes simplex virus, human papillomavirus, Epstein–Barr virus, cytomegalovirus, and respiratory viruses. With the emergence of SARS-CoV-2, new and existing drugs have been intensively evaluated for their potential as COVID-19 medication. Due to its potent immunomodulatory properties, inosine pranobex, an orally administered drug with pleiotropic effects, can, during early treatment, alter the course of the disease. We describe the action of inosine pranobex in the body and give an overview of existing evidence collected to support further efforts to study this drug in a rigorous clinical trial setup.

Effectiveness of treatment of patients with systemic autoimmune diseases on the background of reactivation of persistent Epstein-Barr virus infection

The article presents the study of effectiveness of inosine pranobex (IP) in patients with systemic autoimmune diseases (SAD) on the background of reactivation of persistent Epstein-Barr (EBV) infection. Among 380 patients with SAD (systemic lupus erythematosus, systemic vasculitides, rheumatoid arthritis, psoriasis), in 144 patients (37.9%) the reactivation of persistent EBV infection was detected through virus DNA identification using polymerase chain reaction (PCR) in three biological matrices (blood, saliva, scraping from the lesion site). 48 patients were receiving inosine pranobex at a dose of 50 mg/kg per day for three months. Treatment efficacy was controlled by studying the levels of expression of miR-146а, miR-155, miR EBV (BART-13 and BART-15), TLR9, the quantity of lymphocytes populations and subpopulations. After treatment, PCR results showed a decrease in viral replication in 66.7% of cases. The use of IP contributed to a significant decrease in the level of IgM, IgG specific antibodies, an increase in the level of expression of anti-inflammatory miR-146a, a decrease in the level of expression of pro-inflammatory miR-155 which may signify the strengthening of antiviral control. The study data demonstrated the decrease in the expression of miR EBV (BART-13 and BART-15) and TLR9 on the immunocompetent cells that can also be attributed to the criteria for IP effectiveness. The effectiveness of IP was also proved by the stabilization of cell mechanisms, namely the tendency to normalizing T and B cell populations, decrease in the number of natural killer cells and activated cells (CD25+, CD3+ HLA DR+). On the other hand, the number of lymphocytes with suppressor activity (CD4+25+) remained significantly high mitigating autoimmune aggression. The results of the study show that the use of IP for treating the acute phase of EBV infection contributed to the decrease of repliсative activity of the virus; suppressing the aggressiveness of autoimmune reactions. The decrease in the expression of miR EBV (BART-13 and BART-15) can be recommended as a criterion for the IP effectiveness; the decrease in the expression of TLR9 on immunocompetent cells –as a criterion for suppressing autoimmune reactions.

Upper respiratory tract infection in children – immunostimulating treatment

This paper is a review of publications on viral infections of the upper aerotract in children. Recurring infections can be a consequence of the lack of treatment, inappropriate therapy or accompanying diseases. It is possible that an impaired condition of immunity leads to recurring infections. In this review a great deal of attention has been given to the mechanisms and the various stages of viral infection, and the onset of an organism’s defense mechanisms against viruses. The function of the immunomodulatory and immunostimulatory medical product, namely inosine pranobex has been evaluated in in vitro and in vivo studies. A review of the antiviral activity of inosine pranobex and the onset of cellular and humoral immunity has been presented.

Correction: Beran et al. Inosine Pranobex Significantly Decreased the Case-Fatality Rate among PCR Positive Elderly with SARS-CoV-2 at Three Nursing Homes in the Czech Republic. Pathogens 2020, 9, 1055

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Development, Validation, and Application of the LC-MS/MS Method for Determination of 4-Acetamidobenzoic Acid in Pharmacokinetic Pilot Studies in Pigs

Each drug has pharmacokinetics that must be defined for the substance to be used in humans and animals. Currently, one of the basic analytical tools for pharmacokinetics studies is high-performance liquid chromatography coupled with mass spectrometry. For this analytical method to be fully reliable, it must be properly validated. Therefore, the aims of this study were to develop and validate a novel analytical method for 4-acetamidobenzoic acid, a component of the antiviral and immunostimulatory drug Inosine Pranobex, and to apply the method in the first pharmacokinetics study of 4-acetamidobenzoic acid in pigs after oral administration. Inosine Pranobex was administered under farm conditions to pigs via drinking water 2 h after morning feeding at doses of 20, 40, and 80 mg/kg. For sample preparation, we used liquid–liquid extraction with only one step—protein precipitation with 1 mL of acetonitrile. As an internal standard, we used deuterium labeled 4-acetamidobenzoic acid. The results indicate that the described method is replicable, linear (r2 ≥ 0.99), precise (2.11% to 13.81%), accurate (89% to 98.57%), selective, and sensitive (limit of quantitation = 10 ng/mL). As sample preparation requires only one step, the method is simple, effective, cheap, and rapid. The results of the pilot pharmacokinetics study indicate that the compound is quickly eliminated (elimination half-life from 0.85 to 1.42 h) and rapidly absorbed (absorption half-life from 0.36 to 2.57 h), and that its absorption increases exponentially as the dose is increased.

Novel treatment modalities for pelvic inflammatory disease using immunomodulating therapy

Pelvic inflammatory disease (PID) is a significant issue of public health due to its devastating effects on female reproductive health and fertility. Despite extensive development of medicine and the emergence of novel groups of antibacterial agents, the risks of antibacterial resistance rapidly grow, thus requiring complex treatment of infectious inflammatory disorders caused by bacterial flora. The modulation of immune response is the heart of recently developed treatment modalities for various diseases (infections, oncology etc.). A detailed understanding of molecular immunology contributes to the rational development of novel types of immunotherapy, which can be successfully introduced into clinical practice. Numerous findings demonstrate the efficacy of inosine pranobex for various diseases, in particular, in immunocompromised patients. This medication has proven itself due to good tolerability and the lack of serious side effects. Inosine pranobex being a safe drug that can be used in many treatment schedules, including complex treatment for chronic PID with antibacterial agents. KEYWORDS: inosine pranobex, pelvic inflammatory disease, salpingo-oophoritis, infertility, immunotherapy, sexually transmitted infections, bacterial vaginosis. FOR CITATION: Dobrokhotova Yu.E., Shadrova P.A. Novel treatment modalities for pelvic inflammatory disease using immunomodulating therapy. Russian Journal of Woman and Child Health. 2021;4(2):149–154. DOI: 10.32364/2618-84 30-2021-4-2-149-154.

Immunotherapy of cervical intraepithelial neoplasia associated with human papillomavirus in the COVID-19 pandemic. Clinicians’ view

In the context of the COVID-19 pandemic, the connection between SARS-CoV-2 and other immune-dependent human conditions, including cervical intraepithelial neoplasia (CIN) associated with human papillomavirus (HPV), are being discussed. A review of the literature and the results of observation of patients who are currently receiving therapy with inosine pranobex (IP) according to the standard regimen (as the second stage after organ-preserving cervical surgery) indicate the absence of any abnormalities during the postoperative period. Moreover, publications on the interaction of IP and COVID-19 provide a chance for a favorable outcome regarding not only the treatment of CIN, but also minimizing the inflammatory syndrome in case of SARS-CoV-2 infection. Conclusion. The use of IP as medication-assisted (postoperative) treatment of patients with CIN-HPV in the COVID-19 pandemic conditions is, firstly, as effective with respect to cervical pathology as it is outside the pandemic; secondly, in case of SARS-CoV-2 infection, it can potentially reduce the severity of the course and consequences of respiratory viral infection. Key words: COVID-19, SARS-CoV-2, cervical intraepithelial neoplasia, inosine pranobex

Clinical and immunological rationale for comprehensive approach to prevention and treatment of cervical intraepithelial neoplasia associated with human papillomavirus

A clinical and immunological analysis of the use of antiviral agent Inosine Pranobex (IP) as postoperative drug therapy in patients with cervical intraepithelial neoplasia (CIN) associated with human papillomavirus (HPV) is performed. It is known that IP has a high anti-relapse activity adapted to the mechanisms of HPV elimination (through the sequence of oncoproteins E5, E6 and E7, a decrease in the synthesis of interferons (IFNs) occurs and resistance of HPV-infected cells to IFN is formed). In this work, a number of statements justifying the priority of IP in the treatment of patients with CIN associated with HPV is covered, namely that IP induces trained immunity, differentiation of the Th1 subset of CD4+ T cells and proliferation of CD8+ T cells. Conclusion. Inosine Pranobex should be considered as the medication of choice for postoperative monotherapy in patients with HPV-associated CIN. Inosine Pranobex is characterized by mechanisms of action in both virus-infected cells and through the activation of innate and adaptive immune cells. Key words: CIN, human papillomavirus, inosine pranobex, clinical and immunological aspects, trained immunity

Tubo-ovarian abscesses in reproductive period. Methodological rationale for organ-saving treatment

The issues of complex treatment of patients with tubo-ovarian abscesses (TOA) in the reproductive period were considered, the main component of which is ultrasound minimally invasive surgery – drainage of purulent inflammatory tubo-ovarian mass using transvaginal ultrasound. The technique, indications and contraindications for such treatment were presented. The immune homeostasis of patients with TOA was also studied, and it was shown that they had the expansive nature of proinflammatory changes in cytokine production, as well as activation of the Th1-type lymphocytes with a simultaneous decrease in the Th2-type lymphocytes activity. Therefore, it is appropriate to include immunostimulating agents in the complex of therapeutic measures, particularly inosine pranobex. Conclusion. Drainage of TOA under the control of transvaginal ultrasound can be considered as the choice of treatment of patients of reproductive age. Sixty days after the complex treatment, the proinflammatory nature of cytokine production in these patients changed to mild proinflammatory. Key words: tubo-ovarian abscesses, ultrasound mini-surgery, drainage, inosine pranobex