Role of antiviral therapy in respiratory infections in children: Analysis of clinical and laboratory observations.

Objective. To evaluate the efficacy of therapy for acute respiratory viral infections (ARVIs) in children with antiviral medications: inosine pranobex (Groprinosin, Gedeon Richter) and Kagocel (Kagocel, Niarmedic Pharma LLC) in comparison with symptomatic treatment without etiotropic agents based on clinical and laboratory parameters. Patients and methods. The clinical and laboratory observation was conducted in an outpatient setting in the pre-COVID-19 period between 2018 and 2020. Acute respiratory infections were diagnosed using licensed testing systems by multiplex polymerase chain reaction (PCR) with detection of nucleic acid viral genomes: influenza, rhinovirus, respiratory syncytial virus, metapneumovirus, parainfluenza, seasonal coronaviruses, adenoviruses, and bocavirus). A total of 151 children aged 3 to 15 years were examined and monitored in dynamics, with 78.7% of positive and 21.3% of negative results detected by PCR in the nasopharyngeal and oropharyngeal swabs. The patients were randomized into three groups depending on the antiviral medication prescribed: group 1 (53 children) received Groprinosin;group 2 (52 children) received Kagocel;group 3 (control, 46 children) received only symptomatic therapy without antiviral agents. Results. The study demonstrated a significant positive effect in patients in group 1 treated with Groprinosin (n = 53). At the end of therapy for both mono- and mixed infections, there were 95.8% of negative results (according to PCR diagnosis, that is, the absence of viral genome). In children in group 2 (n = 52) treated with Kagocel, the absence of viral nucleic acids (NAs) was observed less frequently (in 77.3% of cases). In children in group 3 (n = 46) who did not receive etiotropic antiviral therapy, there were only 40.3% of negative results after the end of treatment, and viral NAs were detected in 59.7% of patients. In this case, a 5-day course of Groprinosin was prescribed, after which the PCR results became negative in all patients. Therefore, children with recurrent respiratory infections, mixed infections, and herpesvirus infections require longer therapy. Additionally, a high frequency of ARVI complications was noted in group 3 (5 (10.9%) patients, where otitis was observed in 1 case, sinusitis - in 2 cases, bronchitis - in 2 cases), whereas 1 (1.8%) patient taking Groprinosin had otitis, and 1 (1.9%) patient taking Kagocel had pneumonia. Conclusion. This study was the first to investigate antibody titers to respiratory viruses in dynamics at 3, 6 and 12 months after the onset of ARVI. It showed that the development of antibodies to respiratory viruses is very unstable and does not occur in all patients. Antibodies almost disappeared by the third month after ARVI and were no longer detectable by the sixth month. After 12 months, patients suffered a new ARVI and developed the corresponding antibodies. This information will be especially relevant in conditions of the rise in the incidence of ARVIs, as well as the COVID-19 pandemic observed in recent years.Copyright © 2022, Voprosy Prakticheskoi Pediatrii. All rights reserved.

Role of antiviral therapy in respiratory infections in children: Analysis of clinical and laboratory observations.

Objective. To evaluate the efficacy of therapy for acute respiratory viral infections (ARVIs) in children with antiviral medications: inosine pranobex (Groprinosin, Gedeon Richter) and Kagocel (Kagocel, Niarmedic Pharma LLC) in comparison with symptomatic treatment without etiotropic agents based on clinical and laboratory parameters. Patients and methods. The clinical and laboratory observation was conducted in an outpatient setting in the pre-COVID-19 period between 2018 and 2020. Acute respiratory infections were diagnosed using licensed testing systems by multiplex polymerase chain reaction (PCR) with detection of nucleic acid viral genomes: influenza, rhinovirus, respiratory syncytial virus, metapneumovirus, parainfluenza, seasonal coronaviruses, adenoviruses, and bocavirus). A total of 151 children aged 3 to 15 years were examined and monitored in dynamics, with 78.7% of positive and 21.3% of negative results detected by PCR in the nasopharyngeal and oropharyngeal swabs. The patients were randomized into three groups depending on the antiviral medication prescribed: group 1 (53 children) received Groprinosin;group 2 (52 children) received Kagocel;group 3 (control, 46 children) received only symptomatic therapy without antiviral agents. Results. The study demonstrated a significant positive effect in patients in group 1 treated with Groprinosin (n = 53). At the end of therapy for both mono- and mixed infections, there were 95.8% of negative results (according to PCR diagnosis, that is, the absence of viral genome). In children in group 2 (n = 52) treated with Kagocel, the absence of viral nucleic acids (NAs) was observed less frequently (in 77.3% of cases). In children in group 3 (n = 46) who did not receive etiotropic antiviral therapy, there were only 40.3% of negative results after the end of treatment, and viral NAs were detected in 59.7% of patients. In this case, a 5-day course of Groprinosin was prescribed, after which the PCR results became negative in all patients. Therefore, children with recurrent respiratory infections, mixed infections, and herpesvirus infections require longer therapy. Additionally, a high frequency of ARVI complications was noted in group 3 (5 (10.9%) patients, where otitis was observed in 1 case, sinusitis - in 2 cases, bronchitis - in 2 cases), whereas 1 (1.8%) patient taking Groprinosin had otitis, and 1 (1.9%) patient taking Kagocel had pneumonia. Conclusion. This study was the first to investigate antibody titers to respiratory viruses in dynamics at 3, 6 and 12 months after the onset of ARVI. It showed that the development of antibodies to respiratory viruses is very unstable and does not occur in all patients. Antibodies almost disappeared by the third month after ARVI and were no longer detectable by the sixth month. After 12 months, patients suffered a new ARVI and developed the corresponding antibodies. This information will be especially relevant in conditions of the rise in the incidence of ARVIs, as well as the COVID-19 pandemic observed in recent years.Copyright © 2022, Voprosy Prakticheskoi Pediatrii. All rights reserved.

Evaluation of Inosine-Acedoben-Dimepranol as an immunomodulator in broiler chicks vaccinated with Infectious bronchitis virus vaccine

Protecting livestock against diseases by enhancing its immunity is essential and required in poultry industry. Therefore, the aim of the present study was to evaluate the possible immunoenhancing effects of Inosine-Acedoben-Dimepranol (IAD) in broiler chicks. A total of 150 chicks were used in the present study, divided into 6 groups (25 for each) and subjected to different treatments. It has been found that IAD significantly (P 0.05) increased total leukocytic count, with increased granulocyte (neutrophils, eosinophils, basophils), lymphocyte and monocyte counts compared to control chicks. IAD significantly (P 0.05) increased total protein as a result of increased globulins in plasma when compared with those of control. IAD has been found to significantly (P 0.05) increase immune response of IB vaccine in IAD + IB vaccine-treated groups compared to control measured by ELISA. IAD exhibited antiviral effect indicated by increased survival percent of chicks challenged with virulent IB virus with survival 100% in the groups received IAD large dose plus vaccine. Data of the present study may indicate that supplying chicks with IAD in drinking water is a good recommendation in poultry industry based on its immune enhancing properties.

Inosine: a broad-spectrum anti-inflammatory against SARS-CoV-2 infection-induced acute lung injury via suppressing TBK1 phosphorylation.

SARS-CoV-2-induced cytokine storms constitute the primary cause of COVID-19 progression, severity, criticality, and death. Glucocorticoid and anti-cytokine therapies have been frequently administered to treat COVID-19 but have had limited clinical efficacy in severe and critical cases. Nevertheless, the weaknesses of these treatment modalities have prompted the development of anti-inflammatory therapy against this infection. We found that the broad-spectrum anti-inflammatory agent inosine downregulated proinflammatory IL-6, upregulated anti-inflammatory IL-10, and ameliorated acute inflammatory lung injury caused by multiple infectious agents. Inosine significantly improved survival in mice infected with SARS-CoV-2. It indirectly impeded TANK-binding kinase 1 (TBK1) phosphorylation by binding stimulator of interferon genes (STING) and glycogen synthase kinase-3ß (GSK3ß), inhibited the activation and nuclear translocation of the downstream transcription factors IRF3 and NF-κB, and downregulated IL-6 in the sera and lung tissues of mice infected with lipopolysaccharide (LPS), H1N1, or SARS-CoV-2. Thus, inosine administration is feasible for clinical anti-inflammatory therapy against severe and critical COVID-19. Moreover, targeting TBK1 is a promising strategy for inhibiting cytokine storms and mitigating acute inflammatory lung injury induced by SARS-CoV-2 and other infectious agents.

Isoprinosine along with Favipiravir or Oseltamivir in Patients with Moderate Covid-19 at RSD Dr. Soebandi Jember

Background: Isoprinosine is an immunomodulator that is now being used to treat Covid-19 patients. Objectives: To evaluate Isoprinosine with Favipiravir or Oseltamivir in moderate Covid-19. Methods: In a retrospective observational analysis, in-hospital moderate Covid-19 patients treated between June 2020 and June 2021 were included. Results: Inclusion criteria for 364 patients were met, with 135 receiving Favipiravir-Isoprinosine (Group 1) and 229 receiving Oseltamivir-Isoprinosine (Group 2). In group 1, the majority of patients (58.50%) were female (35.60%), had no comorbidities (71.60%), were discharged with a positive PCR (74.80%), did not require a breathing apparatus (99.26%), had leukocyte levels between 4,5-11,0 (82.22%), lymphocyte levels between 25-33 (34.07%), and were discharged with no ground-glass opacity (34.07%) (54.10%), LOS was 9-13 days (50.37%), while the mortality rate was 0.70%. In group 2, the majority of patients were male (54.10%), with the highest age range being 42-56 years (35.80%), without comorbidities (69.0%), discharged with a positive PCR (72.50 %), and without the need for a breathing apparatus (99.13%), with leukocyte levels ranging from 4.5 - 11.0 (81.22 %), with lymphocyte levels ranging from 25.0 - 33.0 (26.20 %), and were discharged with no ground-glass opacity (49.34 %), LOS was 9 - 13 days (34.06 %), and the mortality rate was 0.87%.Conclusion: In this trial, it was determined that combining isoprinosine with antivirals favipiravir or Oseltamivir could produce significant clinical improvement. [ FROM AUTHOR]

A Comprehensive Investigation of the Current Subacute Sclerosing Panencephalitis (SSPE) Treatment Options to Improve Patient Quality of Life.

Subacute sclerosing panencephalitis (SSPE) is a progressive, disabling, and deadly neurological disorder related to measles (rubeola) infection occurring primarily in children. The slow but persistent viral infection occurs in children or young adults and affects their central nervous system (CNS). There have been plenty of reports on SSPE throughout the world, but it is considered a rare disease in developed countries. This research focuses on comparing the current treatments available to prolong the life of patients for over three years after the onset of SSPE. The goal was to identify possible patterns or trends among the treatments in order to find the best possible method to lengthen a patient's life. The results indicated that interferon alpha, inosine pranobex, and ribavirin display the most effective treatment plan and indicate the most potential in discovering a more effective therapeutic for SSPE.

Efficacy and Safety of Inosine Pranobex in COVID-19 Patients: A Multicenter Phase 3 Randomized Double-Blind, Placebo-Controlled Trial.

Inosine pranobex (IP), an immunomodulatory agent, is used in the treatment of various viral infections. The results of a phase 3 randomized controlled trial are reported, evaluating the efficacy and safety of IP in the treatment of mild to moderate COVID-19. It includes 416 symptomatic patients with confirmed SARS-CoV-2 infection. In addition to a defined standard of care, patients  randomly (1:1) receive either IP 500 mg tablet (IP group) or a matching placebo (placebo group) at 50 mg kg-1 body weight/day rounded to the nearest 500 mg dose (maximum 4 g day-1) administered in 3-4 divided doses for 10 days. Compared to the placebo group, IP group shows significantly higher rates of clinical response (CR) and clinical cure (CC) on Day-6 for both non-hospitalized patients and the total population. IP group shows significantly earlier CR and CC with fewer adverse events and no mortality. Based on these findings and the fact that IP increases natural killer cell-mediated cytotoxicity of virus-infected cells as an early immune response to viral infection and enhances NKG2D ligand expression, it is concluded that IP should be started early to maximize the benefit in mild to moderate COVID-19 patients. (Trial registration number: CTRI/2021/02/030892).

FEATURES OF THE PARAMETERS OF RED BLOOD CELLS AND HEMOSTASIS IN PATIENTS WITH STROKES ASSOCIATED WITH CORONAVIRUS INFECTION

Objective: The purpose is to identify the peculiarities of the parameters of red blood cells (RBC) and hemostasis in patients with strokes associated with coronavirus infection. Design and method: A total of 124 patients (48.5 + 1.9 years) with impairments of cerebral circulation due to COVID-19 (confirmed by positive PCR test) had been examined. Among them, 74 patients had ischemic stroke, 25- transient ischaemic attack, 17- intracerebral hemorrhage, 8- subarachnoid hemorrhage. The parameters of hemostasis were measured by standard methods, electrical, viscoelastic parameters of RBC - by dielectrophoresis. Results: 71 patients (the 1st group) showed signs of intravascular coagulation and thrombosis: accelerated platelet-leukocyte aggregation, increased levels of coagulation products, reduced fibrinolysis activity (p = 0.001-0.04). The levels of D-dimer, fibrinogen, ESR, platelet count were higher in this group compared to the second one (p < 0.01). A moderate increase of RBC summarized rigidity, viscosity was noted. The level of RBC hemolysis was associated with platelet count (r = 0.735,p = 0.03), D-dimer (r = 0.482, p < 0.05), fibrinogen level (r = 0.374, p = 0.04). In 2nd group (53 persons), the markers of thrombosis had moderate deviations. Sharply reduced RBC deformability with increased summarized rigidity, viscosity was dominant coupled with the background of high electrical conductivity of cell membranes compared to the indicators in the 1st group (p < 0.01). There was a decrease of membrane capacity, surface charge, cell dipole moment, polarizability than those in the 1st group (p = 0.0001-0.05). A sharp decrease of RBC deformability creates obstacles to overcoming small-diameter capillaries, leading to violations of microcirculatory blood flow. RBC deformability was associated with levels of ferritin (r = 0.451, p = 0.02), HbA1c (r = 0.480, p = 0.03), uric acid (r = -0.371, p < 0.05), LDL cholesterol (r = 0.461, p = 0.02). Incubation of blood samples in vitro for 10 min with riboflavin, nicotinamide, inosine, which ensures RBC energy metabolism, restored the reduced RBC deformability (p < 0.01), altered cell morphology (p = 0.04), decreased RBC aggregation (p < 0.001). Conclusions: The revealed features of parameters of RBC hemostasis in stroke patients with coronavirus infection are associated with two independent pathogenetic mechanisms: thrombotic and hemorheologic. The thrombotic variant is due to procoagulant state and an activity of inflammation. The hemorheologic variant is caused by decrease of RBC energy metabolism, activity of enzymes.

Therapeutic potential of inosine pranobex in enhancing non-specific antiviral protection in patients with COVID-19

The defense mechanisms of the human body determine non-specific resistance of non-immune cells that comprise the majority of cells in the organism and are exposed to various environmental factors (such as radiation, pollutants, microbial infection), as well as innate and acquired immunity aimed at enhancing the response to external (and internal) stimuli. Inosine is one of the drugs that can strengthen the internal protective reserves of non-immune cells of the human body, primarily against various viruses. Inosine in the form of inosine pranobex is the main component of Groprinosin (Gedeon Richter Pharma LLC). It was shown that protective effect of inosine is attributed to its interaction with the surface adenosine A2A receptor from the family of G-protein-coupled receptors, with activation of the peroxisome proliferator-activated receptor gamma (PPAR-g). This results in inhibition of the mevalonate pathway of cholesterol synthesis and restriction of the viral life cycle of both enveloped (herpes viruses, hepatitis, dengue, mumps, influenza, Ebola, coronaviruses SARS-CoV, MERS-CoV, SARS-CoV-2) and non-enveloped (adenovirus, enterovirus, such as Coxsackie, rotavirus) viruses. Therefore, inosine can be included into the existing clinical protocols or used as an alternative to improve treatment efficacy. © 2021, Dynasty Publishing House. All rights reserved.

O6-[(2″,3″-O-Isopropylidene-5″-O-tbutyldimethylsilyl)pentyl]-5′-O-tbutyldiphenylsilyl-2′,3′-O-isopropylideneinosine

Cyclic adenosine diphosphate ribose (cADPR) is a cyclic nucleotide involved in the Ca2+ homeostasis. In its structure, the northern ribose, bonded to adenosine through an N1 glycosidic bond, is connected to the southern ribose through a pyrophosphate bridge. Due to the chemical instability at the N1 glycosidic bond, new bioactive cADPR derivatives have been synthesized. One of the most interesting analogues is the cyclic inosine diphosphate ribose (cIDPR), in which the hypoxanthine replaced adenosine. The efforts for synthesizing new linear and cyclic northern ribose modified cIDPR analogues led us to study in detail the inosine N1 alkylation reaction. In the last few years, we have produced new flexible cIDPR analogues, where the northern ribose has been replaced by alkyl chains. With the aim to obtain the closest flexible cIDPR analogue, we have attached to the inosine N1 position a 2″,3″-dihydroxypentyl chain, possessing the two OH groups in a ribose-like fashion. The inosine alkylation reaction afforded also the O6-alkylated regioisomer, which could be a useful intermediate for the construction of new kinds of cADPR mimics.

THE ROLE of OXIDATIVE STRESS in the PATHOGENESIS of SOCIALLY SIGNIFICANT HUMAN DISEASES and WAYS of ITS DRUG CORRECTION

The review article describes the role of oxidative stress in the development of socially significant pathologies and approaches to its neutralization. It is shown that the mechanism of oxidative stress is the same in different pathologies, but the consequences of its development may differ. It was found that oxidative stress is one of the main factors in the pathogenesis of severe forms of new coronavirus infection, accompanied by the accumulation of acidic products in the blood and tissues and an increase in the level of Pro-inflammatory cytokines. Various classifications of antioxidant drugs are presented, as well as the pharmacotherapeutic capabilities of domestic low-toxic antioxidants: medicinal product containing succinic acid, inosine, nicotinamide and riboflavin, ethyl methyl hydroxypyridine malate and ethyl methyl hydroxypyridine succinate.

Purinergic signaling elements are correlated with coagulation players in peripheral blood and leukocyte samples from COVID-19 patients.

For over a year, the coronavirus disease 2019 has been affecting the world population by causing severe tissue injuries and death in infected people. Adenosine triphosphate (ATP) and the nicotinamide adenine dinucleotide (NAD +) are two molecules that are released into the extracellular microenvironment after direct virus infection or cell death caused by hyper inflammation and coagulopathy. Also, these molecules are well known to participate in multiple pathways and have a pivotal role in the purinergic signaling pathway. Thus, using public datasets available on the Gene Expression Omnibus (GEO), we analyzed raw proteomics data acquired using mass spectrometry (the gold standard method) and raw genomics data from COVID-19 patient samples obtained by microarray. The data was analyzed using bioinformatics and statistical methods according to our objectives. Here, we compared the purinergic profile of the total leukocyte population and evaluated the levels of these soluble biomolecules in the blood, and their correlation with coagulation components in COVID-19 patients, in comparison to healthy people or non-COVID-19 patients. The blood metabolite analysis showed a stage-dependent inosine increase in COVID-19 patients, while the nucleotides ATP and ADP had positive correlations with fibrinogen and other coagulation proteins. Also, ATP, ADP, inosine, and hypoxanthine had positive and negative correlations with clinical features. Regarding leukocyte gene expression, COVID-19 patients showed an upregulation of the P2RX1, P2RX4, P2RX5, P2RX7, P2RY1, P2RY12, PANX1, ADORA2B, NLPR3, and F3 genes. Yet, the ectoenzymes of the canonical and non-canonical adenosinergic pathway (ENTPD1 and CD38) are upregulated, suggesting that adenosine is produced by both active adenosinergic pathways. Hence, approaches targeting these biomolecules or their specific purinoreceptors and ectoenzymes may attenuate the high inflammatory state and the coagulopathy seen in COVID-19 patients. KEY MESSAGES : Adenosinergic pathways are modulated on leukocytes from COVID-19 patients. Plasmatic inosine levels are increased in COVID-19 patients. ATP, ADP, AMP, hypoxanthine, and inosine are correlated with coagulation players. The nucleotides and nucleosides are correlated with patients' clinical features. The P2 receptors and ectoenzymes are correlated with Tissue factor in COVID-19.

Clinical trials and tribulations: the ordeals of setting up a high intensity clinical trial during COVID19 times

We present our experience with the urgent set-up and execution of a phase 2/3 study to evaluate an investigational medicinal product (ORGN001) in Molybdenum cofactor deficiency type A (MoCDA).MoCDA is a rare inborn error of molybdenum cofactor production resulting in rapidly progressive fatal neurologic damage during the neonatal period. ORGN001 replaces the missing substrate restoring MoCo biosynthesis. It is administered as a daily IV infusion with the first dose given as soon as feasible.A potential subject was identified by prenatal genetic testing on week 12 of pregnancy and was born at 37 weeks via elective C-section. Obstetrics, neonatology and emergency transfer teams were arranged in advance in the local hospital. She was transferred within two hours of birth and was given the first dose of IMP at five hours of life.The set-up of the trial (including R&D approvals) was finalised four weeks before expected birth date in case of prematurity. Early conversations with the intensive care ward ensured appropriate bed space and an admission plan integrating research activities with standard of care. The need for urgent treatment meant careful planning of nursing, pharmacy and medical resources including set up of an on-call rota, training in study protocol and manipulation/administration of the investigational product, and timely EPIC build for prescription and trial specific templates.This is the first time that the Metabolic team takes the lead on a clinical trial of this magnitude providing ad hoc experimental treatment for one patient. Coordination of a multicentre multidisciplinary team in the midst of the COVID19 pandemic was in itself a considerable achievement. Everyone involved was essential to complete the study and achieve the best possible result.The successful execution of this clinical trial shows the adaptation capacity and resilience of GOSH as a research hospital during these difficult times.

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.

Reduced A-to-I editing of endogenous Alu RNAs in lung after SARS-CoV-2 infection.

Due to potential severity of disease caused by SARS-CoV-2 infection, it is critical to understand both mechanisms of viral pathogenesis as well as diversity of host responses to infection. Reduced A-to-I editing of endogenous double-stranded RNAs (dsRNAs), as a result of inactivating mutations in ADAR, produces one form of Aicardi-Goutières Syndrome, with an immune response similar to an anti-viral response. By analyzing whole genome RNA sequencing data, we find reduced levels of A-to-I editing of endogenous Alu RNAs in normal human lung cells after infection by SARS-CoV-2 as well as in lung biopsies from patients with SARS-CoV-2 infections. Unedited Alu RNAs, as seen after infection, induce IRF and NF-kB transcriptional responses and downstream target genes, while edited Alu RNAs as seen in the absence of infection, fail to activate these transcriptional responses. Thus, decreased A-to-I editing may represent an important host response to SARS-CoV-2 infection.

The folate antagonist methotrexate diminishes replication of the coronavirus SARS-CoV-2 and enhances the antiviral efficacy of remdesivir in cell culture models.

The search for successful therapies of infections with the coronavirus SARS-CoV-2 is ongoing. We tested inhibition of host cell nucleotide synthesis as a promising strategy to decrease the replication of SARS-CoV-2-RNA, thus diminishing the formation of virus progeny. Methotrexate (MTX) is an established drug for cancer therapy and to induce immunosuppression. The drug inhibits dihydrofolate reductase and other enzymes required for the synthesis of nucleotides. Strikingly, the replication of SARS-CoV-2 was inhibited by MTX in therapeutic concentrations around 1 µM, leading to more than 1000-fold reductions in virus progeny in Vero C1008 (Vero E6) and ~100-fold reductions in Calu-3 cells. Virus replication was more sensitive to equivalent concentrations of MTX than of the established antiviral agent remdesivir. MTX strongly diminished the synthesis of viral structural proteins and the amount of released virus RNA. Virus replication and protein synthesis were rescued by folinic acid (leucovorin) and also by inosine, indicating that purine depletion is the principal mechanism that allows MTX to reduce virus RNA synthesis. The combination of MTX with remdesivir led to synergistic impairment of virus replication, even at 100 nM MTX. The use of MTX in treating SARS-CoV-2 infections still awaits further evaluation regarding toxicity and efficacy in infected organisms, rather than cultured cells. Within the frame of these caveats, however, our results raise the perspective of a two-fold benefit from repurposing MTX for treating COVID-19. Firstly, its previously known ability to reduce aberrant inflammatory responses might dampen respiratory distress. In addition, its direct antiviral activity described here would limit the dissemination of the virus.

Inosine Pranobex Significantly Decreased the Case-Fatality Rate among PCR Positive Elderly with SARS-CoV-2 at Three Nursing Homes in the Czech Republic.

During the COVID-19 pandemic, the elderly population has been disproportionately affected, especially those in nursing homes (NH). Inosine pranobex (IP) has been previously demonstrated to be effective in treating acute viral respiratory infections. In three NH experiencing the SARS-CoV-2 virus epidemic, we started treatment with IP as soon as clients tested PCR+. In Litovel, CZ, the difference in case-fatality rate (CFR) for the PCR+ group using vs. not using IP was statistically significant, and the odds ratio (OR) was 7.2. When comparing all those taking IP in the three NH vs. the non-drug PCR+ group in Litovel, the odds ratio was lower for all three NH, but still significant at 2.9. The CFR in all three tested NHs, age range 75-84, compared to the CFR in all NHs in the Czech Republic, was significantly reduced (7.5% vs. 18%) (OR: 2.8); there was also a significant difference across all age groups (OR: 1.7). In our study with 301 residents, the CFR was significantly reduced (OR: 2.8) to 11.9% (17/142) in comparison to a study in Ireland with 27.6% (211/764). We think the effect of IP was significant in this reduction; nevertheless, these are preliminary results that need larger-scale trials on COVID-19 patients.