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Two existing blood pressure drugs shown to significantly inhibit coxsackievirus B
Two existing blood pressure drugs, bosentan and valsartan, have been shown to significantly inhibit coxsackievirus B in vitro:
Antiviral effect of Bosentan and Valsartan during coxsackievirus B3 infection of human endothelial cells.
EDIT 2019: In fact a calculation I performed to estimate the in vivo antiviral potency of these two drugs showed that unfortunately their antiviral effect is negligible in vivo. This is because in vivo you cannot achieve the same high concentrations that were used in the in vitro study.
The antiviral action of these two drugs is mediated by their action of lowering the number of coxsackie-adenovirus receptors (CAR) expressed on the cell surface. Coxsackievirus B uses the CAR receptor to enter the cell; so with reduced CAR numbers, the infection is also reduced.
The antiviral effect of bosentan and valsartan will I think likely apply to all Coxsackie B viruses (not just the CVB3 they tested in the study), because all coxsackie B viruses use the CAR receptor for viral entry:
Figure 4 of the study shows that at concentrations of 5 x Cmax, valsartan produces a 3-fold reduction in CVB3 viral titers. Unfortunately, by my calculation (see below), this corresponds to an oral dose of 1,600 mg of valsartan, which is much higher than the maximum dose of 320 mg used for blood pressure treatment. So for this reason, valsartan may not be viable option for its antiviral effects.
But bosentan looks more promising: Figure 4 shows that at concentrations of 1 x Cmax, bosentan produces a 2.5-fold reduction in CVB3 viral titers. By my calculation (see below), this corresponds to an oral dose of 56 mg of bosentan, which is comparable to the regular twice daily 62.5 mg oral does of bosentan used for pulmonary hypertension. So this seems to make bosentan a viable option for treating any coxsackievirus B infection.
Unfortunately bosentan use requires regular monthly liver function checks when you use it. And it is not a cheap drug: the cheapest price I found was 20 x 125 mg tablets for around $200.
Note that the above study was performed in vitro in a cell line, not in vivo, so these antiviral actions may not necessary pan out in patients.
The cells targeted by the drugs are:
Epithelial cells which make up the lining of the mucous membranes of the whole respiratory-gastrointestinal tract (and the lining of serous membranes too).
Endothelial cells which make up the lining of blood vessels.
Epithelial cells are, I believe, a major reservoir for coxsackievirus B infection, so these drugs would appear to hit this virus right in its home territory.
Two existing blood pressure drugs, bosentan and valsartan, have been shown to significantly inhibit coxsackievirus B in vitro:
Antiviral effect of Bosentan and Valsartan during coxsackievirus B3 infection of human endothelial cells.
EDIT 2019: In fact a calculation I performed to estimate the in vivo antiviral potency of these two drugs showed that unfortunately their antiviral effect is negligible in vivo. This is because in vivo you cannot achieve the same high concentrations that were used in the in vitro study.
The antiviral action of these two drugs is mediated by their action of lowering the number of coxsackie-adenovirus receptors (CAR) expressed on the cell surface. Coxsackievirus B uses the CAR receptor to enter the cell; so with reduced CAR numbers, the infection is also reduced.
The antiviral effect of bosentan and valsartan will I think likely apply to all Coxsackie B viruses (not just the CVB3 they tested in the study), because all coxsackie B viruses use the CAR receptor for viral entry:
Note that CVB2 and CVB4 have never been reported to use any other receptor but CAR, but CVB1, CVB3 and CVB5 may bind onto DAF first, and then jump onto CAR in order to enter the cell. Ref: 1
Figure 4 of the study shows that at concentrations of 5 x Cmax, valsartan produces a 3-fold reduction in CVB3 viral titers. Unfortunately, by my calculation (see below), this corresponds to an oral dose of 1,600 mg of valsartan, which is much higher than the maximum dose of 320 mg used for blood pressure treatment. So for this reason, valsartan may not be viable option for its antiviral effects.
But bosentan looks more promising: Figure 4 shows that at concentrations of 1 x Cmax, bosentan produces a 2.5-fold reduction in CVB3 viral titers. By my calculation (see below), this corresponds to an oral dose of 56 mg of bosentan, which is comparable to the regular twice daily 62.5 mg oral does of bosentan used for pulmonary hypertension. So this seems to make bosentan a viable option for treating any coxsackievirus B infection.
Unfortunately bosentan use requires regular monthly liver function checks when you use it. And it is not a cheap drug: the cheapest price I found was 20 x 125 mg tablets for around $200.
Valsartan Dose Calculation
In the paper: Antiviral effect of Bosentan and Valsartan during coxsackievirus B3 infection of human endothelial cells, figure 4a shows that CVB3 titers were reduced by around 3-fold using a valsartan concentration of 5 x Cmax.
In the Supplementary Table S3, they give the valsartan Cmax as 2 μg per ml.
So the valsartan concentration in the cell line used to achieve this 3-fold reduction is 10 μg per ml. Assuming 100% bioavailability, this would require a dose of 400 mg of valsartan. But since bioavailability is just 25%, we would require an oral valsartan dose of 1,600 mg to achieve this. But the maximum daily dose of valsartan for blood pressure is 320 mg.
Valsartan half life is 6 hours.
Bosentan Dose Calculation
In the paper: Antiviral effect of Bosentan and Valsartan during coxsackievirus B3 infection of human endothelial cells, figure 4b shows that CVB3 titers were reduced by around 2.5-fold using a bosentan concentration of 1 x Cmax.
In the Supplementary Table S3, they give the bosentan Cmax as 0.7 μg per ml.
So the bosentan concentration in the cell line used to achieve this 2.5-fold reduction is 0.7 μg per ml. Assuming 100% bioavailability, this would require an oral dose of 28 mg of bosentan. But since bosentan bioavailability is 50%, we would require an oral dose of 56 mg to achieve this. The dose of bosentan for pulmonary hypertension is 62.5 mg orally twice a day for 4 weeks, then increasing to 125 mg orally twice a day.
Bosentan half life is 5 hours.
In the paper: Antiviral effect of Bosentan and Valsartan during coxsackievirus B3 infection of human endothelial cells, figure 4a shows that CVB3 titers were reduced by around 3-fold using a valsartan concentration of 5 x Cmax.
In the Supplementary Table S3, they give the valsartan Cmax as 2 μg per ml.
So the valsartan concentration in the cell line used to achieve this 3-fold reduction is 10 μg per ml. Assuming 100% bioavailability, this would require a dose of 400 mg of valsartan. But since bioavailability is just 25%, we would require an oral valsartan dose of 1,600 mg to achieve this. But the maximum daily dose of valsartan for blood pressure is 320 mg.
Valsartan half life is 6 hours.
Bosentan Dose Calculation
In the paper: Antiviral effect of Bosentan and Valsartan during coxsackievirus B3 infection of human endothelial cells, figure 4b shows that CVB3 titers were reduced by around 2.5-fold using a bosentan concentration of 1 x Cmax.
In the Supplementary Table S3, they give the bosentan Cmax as 0.7 μg per ml.
So the bosentan concentration in the cell line used to achieve this 2.5-fold reduction is 0.7 μg per ml. Assuming 100% bioavailability, this would require an oral dose of 28 mg of bosentan. But since bosentan bioavailability is 50%, we would require an oral dose of 56 mg to achieve this. The dose of bosentan for pulmonary hypertension is 62.5 mg orally twice a day for 4 weeks, then increasing to 125 mg orally twice a day.
Bosentan half life is 5 hours.
Note that the above study was performed in vitro in a cell line, not in vivo, so these antiviral actions may not necessary pan out in patients.
The cells targeted by the drugs are:
Epithelial cells which make up the lining of the mucous membranes of the whole respiratory-gastrointestinal tract (and the lining of serous membranes too).
Endothelial cells which make up the lining of blood vessels.
Epithelial cells are, I believe, a major reservoir for coxsackievirus B infection, so these drugs would appear to hit this virus right in its home territory.
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