Aa
how to use anticholesterol drugs as antivirals
http://www.endfatigue.com/health_articles_c/Cfs_fm-statins_as_possible_new_treatment_for_chronic_fatigue_syndrome.html
i do suggest to use red yeast rice instead of statins because it has almost no sides effects.the content of monacolins in red yeast rice must be at least 6mg.
alt/ast and cpk must be monitored monthly during the use of anticholesterol drugs and coq10 supplements 200-400mg mut be used.
sides effects with red yeast rice are extremely rare so it is not stricly necessary to check alt/ast so often at monacolins dose of 6mg
this won t eradicate hbv but getting ldl to 70mg/dl or lower might lower antigens and hbvdna considerably
i do suggest to use red yeast rice instead of statins because it has almost no sides effects.the content of monacolins in red yeast rice must be at least 6mg.
alt/ast and cpk must be monitored monthly during the use of anticholesterol drugs and coq10 supplements 200-400mg mut be used.
sides effects with red yeast rice are extremely rare so it is not stricly necessary to check alt/ast so often at monacolins dose of 6mg
this won t eradicate hbv but getting ldl to 70mg/dl or lower might lower antigens and hbvdna considerably
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2869246/
from this latest study we know for sure that simvastatin can be sued as a combo antiviral therapy at the highest doses 40mg-80mg to increase antiviral effect, prevent resistance since active on all resistant strains, prevent HCC and cirrhosis too
red yeast rice might have no effect since it is more similar to lovastatin than simvastatin
from this latest study we know for sure that simvastatin can be sued as a combo antiviral therapy at the highest doses 40mg-80mg to increase antiviral effect, prevent resistance since active on all resistant strains, prevent HCC and cirrhosis too
red yeast rice might have no effect since it is more similar to lovastatin than simvastatin
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2869246/
4. Discussion
The HBV infected liver makes a trillion virions every day. SIM is an ideal drug to target the liver since 93% of an oral dose is extracted on the first pass through the liver (Mauro, 1993). Liver tissue levels of SIM have not been reported in humans. In a mammalian model, the hepatic concentration of SIM was observed to be 44X that of serum after 60 minutes (Germershausen et al., 1989). SIM given as a single dose of 40 mg to humans produced peak serum levels of 10 ng/ml; if 44-fold hepatic concentration also occurs in humans, the resulting liver tissue level would then be 3.2 μM (Pentikainen et al., 1992). Thus, the ambient molar concentrations needed to reduce in vitro virion production listed in Table 1 appear to be achievable in vivo with doses that are currently approved by the FDA for cholesterol lowering.
In contrast, NAs target the liver poorly. LMV and ADV have liver/serum ratios of 0.007 and 0.38, respectively (Reddy et al., 2008). Liver/serum ratios for TDF and ETV could not be found in the literature. The excellent liver penetration of SIM may confer an additional benefit when combined with NAs in vivo not evaluable in the current assays.
The total composition of lipid by weight in HBV has been accurately determined only for the abundant surface antigen (HBsAg) component and not for whole virions. Regardless of whether the HBsAg originates from mammalian, human hepatoma cell lines or even yeast, the amount of total lipid constituting HBsAg remains 40% by weight (Diminsky et al., 1997). In any case, this large proportion reveals the substantial need HBV has for cholesterol and its derivatives.
Our observations are similar to those of Delang et al, for an entirely different virus, hepatitis C. They showed synergistic effects for all 10 protease and polymerase inhibitors tested individually in conjunction with simvastatin. However, the latter group did not propose any potential mechanism for this synergistic activity (Delang et al., 2009).
A number of potential mechanisms responsible for the general antiviral effect of statins have been investigated, including inhibiting geranylgeranyl pyrophosphate. Derivatives of the mevalonate pathway, such as geranylgeranyl pyrophosphate are important in the activation of a number of cellular proteins, including small guanosine-5'-triphosphate binding proteins and the Rho family (Ikeda et al., 2006; Schönbeck and Libby, 2004). The specific production of the cholesterol precursor mevalonate by HMG CoA reductase represents a potential bottleneck for blocking cholesterol production. Inhibition of HMG CoA reductase is a well understood pharmacological effect for statins. Others have shown that if this latter reaction is the cause for an effect of a statin, that it can be reversed with addition of mevalonate back to the culture (Ikeda et al., 2006; Ye et al., 2003). The addition of 10uM mevalonate in our test system (Table 2) abolished the anti-HBV effectiveness of SIM. Mevalonate monotherapy did not display an anti-HBV effect nor did it reduce the anti-HBV effectiveness of LMV.
However, since we and others have been unable to make other statins work against HBV, such as fluvastatin (Korba, unpublished results), pravastatin (Bader, unpublished results), or lovastatin (Lin et al., 2003), the reduction of mevalonate is unlikely to be the sole source of anti-HBV effect. Lack of cell penetration by statins cannot explain the lack of anti-HBV activity as fluvastatin, lovastatin and pravastatin have all been shown to penetrate the HepG2 cell line and affect intracellular processes (Ha et al., 2009; Hayashi et al., 1993; Lin et al., 2003).
An anti-cholesterol effect provides a ready explanation as to how SIM inhibits extracellular virion production (i.e. structural assembly) of HBV. How SIM reduces DNA intracellular intermediates of HBV remains to be elucidated. It is unlikely that SIM is working as a polymerase inhibitor, since it does not appear to be structurally related to nucleosides/tides. Thus, the mechanism of anti-HBV action by SIM needs further investigation.
Most hepatologists no longer consider statins to have any significant hepatotoxicity (Cohen et al., 2006). Millions of people have taken SIM safely. While there are rare adverse effects, these side–effects are well delineated. Moreover, it is even possible that SIM may become useful in the treatment of portal hypertension. Abraldes et al have extensively investigated SIM as an agent to treat portal hypertension (Zafra et al., 2004). They recently reported a 30-day double-blind randomized controlled trial using 20 – 40 mg/day of SIM. A significant lowering of portal hypertension and fewer side-effects than placebo were seen in 59 patients with advanced cirrhosis (Abraldes et al., 2009).
Statins have been noted in two large epidemiologic studies in veterans to reduce the risk of HCC by 50% (El-Serag et al., 2009; Khurana et al., 2005). Moreover, because of Veteran's Administration pricing policies during the latter study periods, the predominant statin being prescribed (77%) was SIM (El-Serag et al., 2009). The possibility that SIM may possess anti-HCC activity provides additional rationale for combination therapy.
HBV resistance to the NAs is becoming an increasing problem. We have previously shown equal in vitro efficacy of SIM against wild-type and the clinically relevant HBV resistant strains that encode rtL180M, rtM204V, rtM204I, rtN236T (Bader and Korba, 2008).
4. Discussion
The HBV infected liver makes a trillion virions every day. SIM is an ideal drug to target the liver since 93% of an oral dose is extracted on the first pass through the liver (Mauro, 1993). Liver tissue levels of SIM have not been reported in humans. In a mammalian model, the hepatic concentration of SIM was observed to be 44X that of serum after 60 minutes (Germershausen et al., 1989). SIM given as a single dose of 40 mg to humans produced peak serum levels of 10 ng/ml; if 44-fold hepatic concentration also occurs in humans, the resulting liver tissue level would then be 3.2 μM (Pentikainen et al., 1992). Thus, the ambient molar concentrations needed to reduce in vitro virion production listed in Table 1 appear to be achievable in vivo with doses that are currently approved by the FDA for cholesterol lowering.
In contrast, NAs target the liver poorly. LMV and ADV have liver/serum ratios of 0.007 and 0.38, respectively (Reddy et al., 2008). Liver/serum ratios for TDF and ETV could not be found in the literature. The excellent liver penetration of SIM may confer an additional benefit when combined with NAs in vivo not evaluable in the current assays.
The total composition of lipid by weight in HBV has been accurately determined only for the abundant surface antigen (HBsAg) component and not for whole virions. Regardless of whether the HBsAg originates from mammalian, human hepatoma cell lines or even yeast, the amount of total lipid constituting HBsAg remains 40% by weight (Diminsky et al., 1997). In any case, this large proportion reveals the substantial need HBV has for cholesterol and its derivatives.
Our observations are similar to those of Delang et al, for an entirely different virus, hepatitis C. They showed synergistic effects for all 10 protease and polymerase inhibitors tested individually in conjunction with simvastatin. However, the latter group did not propose any potential mechanism for this synergistic activity (Delang et al., 2009).
A number of potential mechanisms responsible for the general antiviral effect of statins have been investigated, including inhibiting geranylgeranyl pyrophosphate. Derivatives of the mevalonate pathway, such as geranylgeranyl pyrophosphate are important in the activation of a number of cellular proteins, including small guanosine-5'-triphosphate binding proteins and the Rho family (Ikeda et al., 2006; Schönbeck and Libby, 2004). The specific production of the cholesterol precursor mevalonate by HMG CoA reductase represents a potential bottleneck for blocking cholesterol production. Inhibition of HMG CoA reductase is a well understood pharmacological effect for statins. Others have shown that if this latter reaction is the cause for an effect of a statin, that it can be reversed with addition of mevalonate back to the culture (Ikeda et al., 2006; Ye et al., 2003). The addition of 10uM mevalonate in our test system (Table 2) abolished the anti-HBV effectiveness of SIM. Mevalonate monotherapy did not display an anti-HBV effect nor did it reduce the anti-HBV effectiveness of LMV.
However, since we and others have been unable to make other statins work against HBV, such as fluvastatin (Korba, unpublished results), pravastatin (Bader, unpublished results), or lovastatin (Lin et al., 2003), the reduction of mevalonate is unlikely to be the sole source of anti-HBV effect. Lack of cell penetration by statins cannot explain the lack of anti-HBV activity as fluvastatin, lovastatin and pravastatin have all been shown to penetrate the HepG2 cell line and affect intracellular processes (Ha et al., 2009; Hayashi et al., 1993; Lin et al., 2003).
An anti-cholesterol effect provides a ready explanation as to how SIM inhibits extracellular virion production (i.e. structural assembly) of HBV. How SIM reduces DNA intracellular intermediates of HBV remains to be elucidated. It is unlikely that SIM is working as a polymerase inhibitor, since it does not appear to be structurally related to nucleosides/tides. Thus, the mechanism of anti-HBV action by SIM needs further investigation.
Most hepatologists no longer consider statins to have any significant hepatotoxicity (Cohen et al., 2006). Millions of people have taken SIM safely. While there are rare adverse effects, these side–effects are well delineated. Moreover, it is even possible that SIM may become useful in the treatment of portal hypertension. Abraldes et al have extensively investigated SIM as an agent to treat portal hypertension (Zafra et al., 2004). They recently reported a 30-day double-blind randomized controlled trial using 20 – 40 mg/day of SIM. A significant lowering of portal hypertension and fewer side-effects than placebo were seen in 59 patients with advanced cirrhosis (Abraldes et al., 2009).
Statins have been noted in two large epidemiologic studies in veterans to reduce the risk of HCC by 50% (El-Serag et al., 2009; Khurana et al., 2005). Moreover, because of Veteran's Administration pricing policies during the latter study periods, the predominant statin being prescribed (77%) was SIM (El-Serag et al., 2009). The possibility that SIM may possess anti-HCC activity provides additional rationale for combination therapy.
HBV resistance to the NAs is becoming an increasing problem. We have previously shown equal in vitro efficacy of SIM against wild-type and the clinically relevant HBV resistant strains that encode rtL180M, rtM204V, rtM204I, rtN236T (Bader and Korba, 2008).
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2869246/
5. Conclusions
We report, for the first time, significant in vitro suppression of HBV in a whole virus assay by a particular statin, simvastatin (SIM). We have explored possible mechanisms for the anti-HBV effect of SIM. We also demonstrate the ability of SIM to work synergistically with lamivudine (LMV), adefovir (ADV), tenofovir (TDF) and entecavir (ETV) to further inhibit HBV replication. The in vitro anti-HBV synergism of simvastatin with nucleos(t)ide analogs is robust.
Other evidence suggests that the clinical translation of this observation may lead not only to increased antiviral efficacy, but also slowing of viral resistance and reduction of HCC. The in vitro potential reported here warrants further testing in humans as another possible approach for the eventual reduction of cancer and cirrhosis caused by the most common chronic infectious disease in the world.
5. Conclusions
We report, for the first time, significant in vitro suppression of HBV in a whole virus assay by a particular statin, simvastatin (SIM). We have explored possible mechanisms for the anti-HBV effect of SIM. We also demonstrate the ability of SIM to work synergistically with lamivudine (LMV), adefovir (ADV), tenofovir (TDF) and entecavir (ETV) to further inhibit HBV replication. The in vitro anti-HBV synergism of simvastatin with nucleos(t)ide analogs is robust.
Other evidence suggests that the clinical translation of this observation may lead not only to increased antiviral efficacy, but also slowing of viral resistance and reduction of HCC. The in vitro potential reported here warrants further testing in humans as another possible approach for the eventual reduction of cancer and cirrhosis caused by the most common chronic infectious disease in the world.
Simvastatin potentiates the anti-hepatitis B virus activity
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2869246/
http://content.karger.com/ProdukteDB/produkte.asp?Doi=321892
Statins Reduce Dengue Virus Production via Decreased Virion Assembly
Abstract
Background: Most of the effects of statins can be explained by pleiotropic effects independent of their lowering of serum cholesterol; in some cases, these effects have been shown to be a result of the role of statins in the prenylation of cellular proteins, some of which are involved in the life cycle of animal viruses. This study evaluated the potential antiviral activity of lovastatin (LOV) against dengue virus (DENV) infection of epithelial and endothelial cells (VERO cells, epithelial cells derived from African green monkey kidney, and HMEC-1 cells, human dermal microvascular endothelial cells). Methods: To evaluate its potential antiviral effects, LOV was used before, during and after inoculation of cell cultures with DENV. Results: Before and after viral inoculation, LOV caused a reduction in virus yield (80% for HMECs and 25% for VERO cells). However, with LOV treatment after inoculation induced a marked increase (2- to 9-fold) in viral-positive RNA while the amount of viral protein increased only by 13–23%. A moderate reduction (1 log unit) in viral titer occurred concurrent with the increase in DENV genomic RNA and protein within the cells. Conclusions: According to our results, LOV appears to have a greater effect on viral assembly than on replication, resulting in the cellular presence of viral genomic RNA and proteins that fail to take the normal assembly pathway.
http://www.sovegastro.com/pdf/Fluvastatina%20inhibe%20replicacion%20HVC%20en%20humanos.pdf
good article about the use of fluvastatin with hcv, as regards hbv simvastatin and lovastatin are the only statins i have seen studied on hbv (among the two sim at 80mg has the strongest effect)
Low cholesterol gives opportunity for virus to replicate?
no it takes away the possibility that infected cells can make virions and antigens.the same thing is done by natural or injected interferon, interferon lowers cholesterol so that infected cells cannot make the virus
so if you lower cholesterol to low levels the virus has..let's say no food to replicate, this won t clear infection but will lower virus and antigens quantity.lowering cholesterol a bit has no effect, only lowering the maximum has an effect
red yeast rice?
check online, it is an asian food that contains natural statins
no it takes away the possibility that infected cells can make virions and antigens.the same thing is done by natural or injected interferon, interferon lowers cholesterol so that infected cells cannot make the virus
so if you lower cholesterol to low levels the virus has..let's say no food to replicate, this won t clear infection but will lower virus and antigens quantity.lowering cholesterol a bit has no effect, only lowering the maximum has an effect
red yeast rice?
check online, it is an asian food that contains natural statins
Sorry, I don't understand. Low cholesterol gives opportunity for virus to replicate? And what is red yeast rice?
an anticholesterol supplement that is more potent than statin drugs.
US FDA blocked a component of this supplement, monacolin, so it maybe less potent in US, but still working
european or italian supplements have standardizied monacolin so these are more potent, the combined use of monacolins 3mg daily (which i extremely low), liposomal glutathione made my ldl down from 130 to 106 in 4 weeks.
now i am increasing monacolins to 6mg and adding vitamin b5 (pantethine) and lycopene which are both reported as potent lowering cholesterol substances.b5 from in vitro shows some antiviral effect and lycopene is a spotent as low dose statins.
since research showed that simv had antiviral effect on hbv at maximum dose of 80mg i am trying to use safer supplements to reach the same result.a goal of ldl 70mg/dl or little lower is the same that can be reached on high dose statins
a minimum ldl of 25dl/ml is needed for body functions but i will stay at a minimum of 50mg/dl.
also remember to lowering cholesterol to these low levels by supplements or drugs is also benificial for general health, while having such low cholesterol naturally is not a good sign of health because it may mean some cancer or virus is making use of it
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