How an increase in the copy number of HSV-1 during latency can cause Alzheimer's disease: the viral and cellular dynamics according to the microcompetition model.

Numerous studies observed a link between the herpes smplex virus-1 (HSV-1) and Alzheimer's disease. However, the exact viral and cellular dynamics that lead from an HSV-1 infection to Alzheimer's disease are unknown. In this paper, we use the microcompetition model to formulate these dynamics by connecting seemingly unconnected observations reported in the literature. We concentrate on four pathologies characteristic of Alzheimer's disease. First, we explain how an increase in the copy number of HSV-1 during latency can decrease the expression of BECN1/Beclin1, the degradative trafficking protein, which, in turn, can cause a dysregulation of autophagy and Alzheimer's disease. Second, we show how an increase in the copy number of the latent HSV-1 can decrease the expression of many genes important for mitochondrial genome metabolism, respiratory chain, and homeostasis, which can lead to oxidative stress and neuronal damage, resulting in Alzheimer's disease. Third, we describe how an increase in this copy number can reduce the concentration of the NMDA receptor subunits NR1 and NR2b (Grin1 and Grin2b genes), and brain derived neurotrophic factor (BDNF), which can cause an impaired synaptic plasticity, Aß accumulation and eventually Alzheimer's disease. Finally, we show how an increase in the copy number of HSV-1 in neural stem/progenitor cells in the hippocampus during the latent phase can lead to an abnormal quantity and quality of neurogenesis, and the clinical presentation of Alzheimer's disease. Since the current understanding of the dynamics and homeostasis of the HSV-1 reservoir during latency is limited, the proposed model represents only a first step towards a complete understanding of the relationship between the copy number of HSV-1 during latency and Alzheimer's disease.

How microcompetition with latent viruses can cause α synuclein aggregation, mitochondrial dysfunction, and eventually Parkinson's disease.

The cause of most Parkinson's disease cases is unknown. However, it is well documented that mitochondrial dysfunction and misfolded α synuclein aggregation are important cellular abnormalities associated with the disease. In this paper, we use the microcompetition model to show how latent viruses, which infect the central and peripheral nervous systems, can cause the observed mitochondrial dysfunction and excess α synuclein aggregation, and eventually, Parkinson's disease.

Effects of Gene-Eden-VIR and Novirin on SARS-CoV: Implications for COVID-19.

The coronavirus (SARS-CoV-2), which causes COVID-19, is a betacoronavirus closely related to the human severe acute respiratory syndrome (SARS)-coronavirus (SARS-CoV). The recent COVID-19 outbreak created an urgent need for treatment. To expedite the development of such treatment, pharmaceutical companies and government agencies are currently testing several existing drugs for their effect on the virus. Gene-Eden-VIR and Novirin are natural, broad-spectrum, antiviral treatments proven to be safe and effective in several clinical studies. In this article, we present evidence indicating that the 5 Gene-Eden-VIR/Novirin ingredients have anti-betacoronavirus, and specifically, anti-SARS-CoV effects. We consider this evidence as a first indication of the anti-coronavirus effects of Gene-Eden-VIR/Novirin. Next, we are planning to conduct a clinical study with users of the treatments to test the effects of Gene-Eden-VIR/Novirin on individuals at risk and those infected with the virus.

Dynamics of sequestering the limiting p300/CBP, viral cis-regulatory elements, and disease.

Many studies showed that the p300/CBP coactivator is limiting. Here we review three studies that showed how transcription complexes formed on viral cis-regulator elements compete with cellular transcription complexes by sequestrating the p300/CBP coactivator. According to the microcompetition model, this sequestering can cause disease. We use the microcompetition model to explain how a specific type of sequestering, caused by a latent virus that has an active cis-regulatory element in its promoter/enhancer that binds the transcription complex p300/CBP ·GABP can cause diseases such as cancer, atherosclerosis, diabetes, and certain autoimmune diseases.

How can the latent cytomegalovirus cause an increase in all-cause mortality? An answer based on the microcompetition model.

Many studies showed the existence of a positive association between cytomegalovirus (CMV) seropositivity and all-cause mortality. In this paper, we use the microcompetition model to explain how the latent CMV sequesters the limiting GABP∙p300/CBP transcription complex, which causes abnormal cellular gene expression, a chronic disease and mortality. Since most people harbour the latent CMV, we urge further research on this topic.

Expression of Concern to: Clinical study of Gene-Eden-VIR/Novirin in genital herpes: suppressive treatment safely decreases the duration of outbreaks in both severe and mild cases.

The Editor of this journal has published this Expression of Concern to alert readers that, following publication of the article [1], it came to light that there were undeclared competing interests that have a direct impact on the article and the strength of its findings. In addition, post publication peer review has indicated that the conclusions may not be supported by the results due to methodological flaws in the study. Pending further investigation of these concerns, further editorial action may be taken. The authors have not responded to any correspondence about this Expression of Concern.

How latent viruses cause breast cancer: An explanation based on the microcompetition model.

Most breast cancer cases show a decrease in the concentration of the breast cancer type 1 susceptibility protein (BRCA1). However, only a small portion of these cases have a mutated BRCA1 gene. Although many attempts have been made to identify the reason for the decrease in BRCA1 concentration in sporadic, non-heritable breast cancer cases, the cause is still unknown. In this review, we use the Microcompetition Model to explain how certain latent viruses, which are frequently detected in breast cancer tumors, can decrease the expression of the BRCA1 gene and cause the development of breast tumors.

Latent viruses can cause disease by disrupting the competition for the limiting factor p300/CBP.

CBP and p300 are histone acetyltransferase coactivators that control the transcription of numerous genes in humans, viruses, and other organisms. Although two separate genes encode CBP and p300, they share a 61% sequence identity, and they are often mentioned together as p300/CBP. Zhou et al. showed that under hypoxic conditions, HIF1α and the tumor suppressor p53 compete for binding to the limiting p300/CBP coactivator. Jethanandani & Kramer showed that δEF1 and MYOD genes compete for the limited amount of p300/CBP in the cell. Bhattacharyya et al. showed that the limiting availability of p300/CBP in the cell serves as a checkpoint for HIF1α activity. Here, we use the microcompetition model to explain how latent viruses with a specific viral cis-regulatory element in their promoter/enhancer can disrupt this competition, causing diseases such as cancer, diabetes, atherosclerosis, and obesity.

Clinical Trial of Herbal Treatment Gene-Eden-VIR/Novirin in Oral Herpes.

BACKGROUND: Our previous articles showed that suppressive or preventive treatment with the herbal Gene-Eden-VIR/Novirin reduced the number and duration of genital herpes outbreaks with no adverse effects. These studies also revealed that the herbal Gene-Eden-VIR/Novirin is mostly superior to acyclovir, valacyclovir, and famciclovir drugs in genital herpes. This study tested the effect of Gene-Eden-VIR/Novirin in oral herpes (also called cold sores and fever blisters). METHODS: The framework of the study was a retrospective chart review. The study included 68 participants. The participants took 1 to 4 capsules per day over a period of 2 to 36 months. The study included 2 Food and Drug Administration-recommended controls: baseline and a no-treatment. RESULTS: Gene-Eden-VIR/Novirin was effective in 89.3% of participants. The treatment reduced the mean number of outbreaks per year from 6.0 and 3.6 in the control groups to 2.0 in the treatment group ( P < .0001 and P = .07, respectively). Gene-Eden-VIR/Novirin reduced the mean duration of outbreaks from 9.8 and 5.8 days in the control groups to 3.2 days in the treatment group ( P < .0001 and P = .02, respectively). There were no reports of adverse experiences. Gene-Eden-VIR/Novirin was compared to acyclovir and valacyclovir in 6 tests. In all tests, Gene-Eden-VIR/Novirin showed higher efficacy. Gene-Eden-VIR/Novirin also showed superior safety. CONCLUSIONS: This clinical study showed that suppressive or preventive treatment with the herbal Gene-Eden-VIR/Novirin reduced the number and duration of outbreaks in oral herpes without any adverse effects. The study also showed that the herbal Gene-Eden-VIR/Novirin had better clinical effects than acyclovir and valacyclovir, the leading drugs in the category. Based on these results, we recommend using the herbal Gene-Eden-VIR/Novirin as preventive treatment for oral herpes and, specifically, as an alternative to the acyclovir and valacyclovir drugs.

Male-pattern baldness, common latent viruses, and microcompetition.

Many studies link the development of androgen-related disorders to the overexpression of two proteins, 5α-reductase and androgen receptor (AR). In this commentary, we use microcompetition to explain how common latent viruses can cause transcription factor deficiency, overexpression of 5α-reductase and AR, and male-pattern baldness.

Human papillomavirus (HPV): systemic treatment with Gene-Eden-VIR/Novirin safely and effectively clears virus.

PURPOSE: This paper reports the results of a clinical study that tested the effect of systemic treatment with the botanical product Gene-Eden-VIR/Novirin on the clearance rate (also called time to clearance) of the human papillomavirus (HPV). The study compared the clearance rate in treated and untreated individuals suffering from a symptomatic HPV infection. The data on the untreated individuals were obtained by reverse engineering of the Kaplan-Meier figures in five published papers. MATERIALS AND METHODS: The study included 59 treated participants. All participants were suffering from a symptomatic HPV infection prior to the commencement of treatment. The treatment was one to four capsules of Gene-Eden-VIR/Novirin per day. The duration of treatment was 2-12 months. The study included five groups of external controls with diverse characteristics. RESULTS: The mean time to clearance in Gene-Eden-VIR/Novirin-treated individuals was 5.1 months or 151.5 days (95% CI: 4.2-5.9 months or 95% CI: 125.7-177.3 days, respectively). The median time to clearance was 3.5 months. The mean time to clearance in the five untreated groups ranged from 6.9 to 20.0 months (P<0.0001 for the difference between treatment group and each untreated group). Also, 100% of the participants in the treatment group were HPV free at the end of 12 months vs 53%, 52%, 65%, 20%, and 77% in the untreated control groups. The treated participants reported no adverse experiences. CONCLUSION: This clinical study has two major contributions. First, it showed that systemic treatment with the natural Gene-Eden-VIR/Novirin decreased the time to HPV clearance, increased the percentage of HPV-free individuals, and caused no adverse experiences in individuals suffering from a symptomatic HPV infection. Since there are no other systemic treatments for symptomatic HPV infections, this study presents highly valuable information on the clinical effects of the first treatment in this category. Second, the study presents a new method for conducting clinical studies that addresses one of the major deficiencies associated with the practice of the randomized controlled trial method.

Clinical study of Gene-Eden-VIR/Novirin in genital herpes: suppressive treatment safely decreases the duration of outbreaks in both severe and mild cases.

BACKGROUND: We conducted a clinical study that tested the effect of suppressive treatment with the botanical product Gene-Eden-VIR/Novirin on genital herpes. Our previous paper showed that the treatment decreased the number of genital herpes outbreaks without any side effects. It also showed that the clinical effects of Gene-Eden-VIR/Novirin are mostly better than those reported in the studies that tested acyclovir, valacyclovir, and famciclovir. The current paper reports the effect of suppressive treatment with Gene-Eden-VIR/Novirin on the duration of outbreaks, in severe and mild genital herpes cases. METHODS: The framework was a retrospective chart review. The population included 137 participants. The treatment was 1-4 capsules per day. The duration of treatment was 2-48 months. The study included three controls: baseline, no-treatment, and dose-response. RESULTS: The treatment decreased the duration of outbreaks in 87 % of participants and decreased the mean duration of outbreaks from 8.77 days and 6.7 days in the control groups to 2.87 days in the treatment group (P < 0.001, both groups). All participants reported no adverse experiences. CONCLUSIONS: This paper shows that suppressive treatment with Gene-Eden-VIR/Novirin decreased the duration of genital herpes outbreaks, in both severe and mild cases, without any side effects. Based on the results reported in this and our previous paper, we recommend suppressive treatment with Gene-Eden-VIR/Novirin as a natural alternative to both suppressive and episodic treatments with current drugs, in both severe and mild genital herpes cases. Trial registration ClinicalTrials.gov NCT02715752 Registered 17 March 2016 Retrospectively Registered.

Clinical study in genital herpes: natural Gene-Eden-VIR/Novirin versus acyclovir, valacyclovir, and famciclovir.

BACKGROUND: This paper reports the results of a clinical study that tested the effect of suppressive treatment with the botanical product Gene-Eden-VIR/Novirin on the number of genital herpes outbreaks. The results in this study were compared to those published in clinical studies of acyclovir, valacyclovir, and famciclovir. METHODS: The framework was a retrospective chart review. The population included 139 participants. The treatment was one to four capsules of Gene-Eden-VIR/Novirin per day. The duration of treatment was 2-48 months. The study included three controls recommended by the US Food and Drug Administration (FDA): baseline, no treatment, and dose response. RESULTS: The treatment decreased the number of outbreaks per year in 90.8% of the participants. The treatment also decreased the mean number of outbreaks per year from 7.27 and 5.5 in the control groups to 2.39 (P<0.0001 and P<0.001, respectively). The treated participants reported no adverse experiences. Out of the 15 tests that compared Gene-Eden-VIR/Novirin to the three drugs, Gene-Eden-VIR/Novirin had superior efficacy in eight tests, inferior efficacy in three tests, and comparable efficacy in four tests. Gene-Eden-VIR/Novirin also had superior safety. CONCLUSION: The clinical study showed that the natural Gene-Eden-VIR/Novirin decreases the number of genital herpes outbreaks without any side effects. The study also showed that the clinical effects reported in this study are mostly better than those reported in the reviewed studies of acyclovir, valacyclovir, and famciclovir.

3-Econsystems: MicroRNAs, Receptors, and Latent Viruses; Some Insights Biology Can Gain from Economic Theory.

This mini-review describes three biological systems. All three include competing molecules and a limiting molecule that binds the competing molecules. Such systems are extensively researched by economists. In fact, the issue of limited resources is the defining feature of economic systems. Therefore, we call these systems "econsystems." In an econsystem, the allocation of the limiting molecule between the competing molecules determines the behavior of the system. A cell is an example of an econsystem. Therefore, a change in the allocation of a limiting molecule as a result of, for instance, an abnormal change in the concentration of one of the competing molecules, may result in abnormal cellular behavior, and disease. The first econsystem described in this mini-review includes a long non-coding RNA and a messenger RNA (lncRNA and mRNA). The limiting molecule is a microRNA (miRNA). The lncRNA and mRNA are known as competing endogenous RNAs (ceRNAs). The second econsystem includes two receptors, and the limiting molecule is a ligand. The third econsystem includes a cis-regulatory element of a latent virus and that of a human gene. The limiting molecule is a transcription complex that binds both cis-elements.

The latent cytomegalovirus decreases telomere length by microcompetition.

Reduced telomere length has been associated with aging and age-related diseases. Latent infection with the Cytomegalovirus (CMV) induces telomere shortening in the infected cells. Latent CMV infection may cause reduced telomere length via GABP transcription factor deficiency, according to the Microcompetition Theory. Microcompetition and viral-induced transcription factor deficiency is important since most people harbor a latent viral infection.