'Researchers develop new compound to fight cytomegalovirus'

Remy

Administrator
A Retro94-based compound may prevent a common and sometimes fatal virus -- human cytomegalovirus (CMV) -- from reproducing and help to protect immunocompromised patients, such as those with HIV, on chemotherapy, with transplants, and infants from the effects of the disease, according to Penn State College of Medicine researchers.

New therapies for CMV are needed, said Nicholas J. Buchkovich, assistant professor of microbiology and immunology and lead researcher. The current treatments for CMV in immunosuppressed patients can have toxic side effects, and emerging mutations in the virus are developing resistance to existing therapies.
The Retro94-based compound effectively stops the virus from making copies of itself. This means that immunocompromised patients with active CMV infection could be treated with anti-viral medication or even protected from the virus reactivating in the body before it occurs. The results were recently published in the Journal of Virology.

While about 50 percent of Americans have been infected with CMV, in developing countries this number can approach 100 percent of the adult population. Although the virus is generally harmless, it can cause serious health problems in people with suppressed immune systems.

CMV also is the most common infection present from birth, and infants born with CMV can suffer from hearing loss, vision problems, microcephaly -- a condition that involves an abnormal smallness of the head -- and intellectual deficits. CMV is the leading nongenetic cause of deafness and results in the deaths of hundreds of children annually. CMV also has a major impact on morbidity and mortality of transplant patients and is often associated with transplant rejection.

After CMV infects a human cell, it creates a compartment where proteins are assembled into infectious viral particles. These virus particles then escape the cell to invade new ones, spreading infection. A key goal for the researchers is to understand how this assembly compartment forms. The level of Syntaxin 5 protein is increased in CMV-infected cells. The virus appears to recruit this protein from the host cell to generate the assembly compartment.

When the researchers used a genetic technique called miRNA knockdown to decrease this protein in CMV-infected cells, the compartments formed irregular shapes and produced fewer new virus particles.

Previous work suggested that the Retro94 molecule interferes with Syntaxin 5. Knowing this, the researchers then developed, in collaboration with Dhimant Desai and Shantu Amin in the department of pharmacology, a Retro94-based compound and tested its effect in CMV-infected cells in the laboratory.

"We knew of a compound that modulates Syntaxin 5," Buchkovich explained. "We tested to see if that would inhibit the formation of the assembly compartment and, in turn, inhibit the actual production of the virus. That is, in fact, what we found."

The CMV assembly compartments also formed irregularly in the presence of the compound. Importantly, the compound did not harm the host cells.

The findings suggest that Retro94 should be studied further as a potential effective and safe therapy against human CMV that interferes with the viral assembly compartment.

Buchkovich is now planning to test the compound in an animal model.
Story Source:
Materials provided by Penn State. Original written by Abby Sajid. Note: Content may be edited for style and length.
Journal Reference:
  1. Linda Cruz, Nicholas T. Streck, Kevin Ferguson, Trisha Desai, Dhimant H. Desai, Shantu G. Amin, Nicholas J. Buchkovich. Potent Inhibition of Human Cytomegalovirus by Modulation of Cellular SNARE Syntaxin 5. Journal of Virology, 2017; 91 (1): e01637-16 DOI: 10.1128/JVI.01637-16
 

Cort

Founder of Health Rising and Phoenix Rising
Staff member
A Retro94-based compound may prevent a common and sometimes fatal virus -- human cytomegalovirus (CMV) -- from reproducing and help to protect immunocompromised patients, such as those with HIV, on chemotherapy, with transplants, and infants from the effects of the disease, according to Penn State College of Medicine researchers.

New therapies for CMV are needed, said Nicholas J. Buchkovich, assistant professor of microbiology and immunology and lead researcher. The current treatments for CMV in immunosuppressed patients can have toxic side effects, and emerging mutations in the virus are developing resistance to existing therapies.
The Retro94-based compound effectively stops the virus from making copies of itself. This means that immunocompromised patients with active CMV infection could be treated with anti-viral medication or even protected from the virus reactivating in the body before it occurs. The results were recently published in the Journal of Virology.

While about 50 percent of Americans have been infected with CMV, in developing countries this number can approach 100 percent of the adult population. Although the virus is generally harmless, it can cause serious health problems in people with suppressed immune systems.

CMV also is the most common infection present from birth, and infants born with CMV can suffer from hearing loss, vision problems, microcephaly -- a condition that involves an abnormal smallness of the head -- and intellectual deficits. CMV is the leading nongenetic cause of deafness and results in the deaths of hundreds of children annually. CMV also has a major impact on morbidity and mortality of transplant patients and is often associated with transplant rejection.

After CMV infects a human cell, it creates a compartment where proteins are assembled into infectious viral particles. These virus particles then escape the cell to invade new ones, spreading infection. A key goal for the researchers is to understand how this assembly compartment forms. The level of Syntaxin 5 protein is increased in CMV-infected cells. The virus appears to recruit this protein from the host cell to generate the assembly compartment.

When the researchers used a genetic technique called miRNA knockdown to decrease this protein in CMV-infected cells, the compartments formed irregular shapes and produced fewer new virus particles.

Previous work suggested that the Retro94 molecule interferes with Syntaxin 5. Knowing this, the researchers then developed, in collaboration with Dhimant Desai and Shantu Amin in the department of pharmacology, a Retro94-based compound and tested its effect in CMV-infected cells in the laboratory.

"We knew of a compound that modulates Syntaxin 5," Buchkovich explained. "We tested to see if that would inhibit the formation of the assembly compartment and, in turn, inhibit the actual production of the virus. That is, in fact, what we found."

The CMV assembly compartments also formed irregularly in the presence of the compound. Importantly, the compound did not harm the host cells.

The findings suggest that Retro94 should be studied further as a potential effective and safe therapy against human CMV that interferes with the viral assembly compartment.

Buchkovich is now planning to test the compound in an animal model.
Story Source:
Materials provided by Penn State. Original written by Abby Sajid. Note: Content may be edited for style and length.
Journal Reference:
  1. Linda Cruz, Nicholas T. Streck, Kevin Ferguson, Trisha Desai, Dhimant H. Desai, Shantu G. Amin, Nicholas J. Buchkovich. Potent Inhibition of Human Cytomegalovirus by Modulation of Cellular SNARE Syntaxin 5. Journal of Virology, 2017; 91 (1): e01637-16 DOI: 10.1128/JVI.01637-16
Good news...

I wonder if there's any chance this would be helpful against other herpesviruses?
 

Hip

Well-Known Member
The flavonoid compound tricin (found in rice bran) has the most extraordinarily potent antiviral effect against cytomegalovirus.

The antiviral potency of a compound is usually measured in terms of its selectivity index (also called the therapeutic index). The selectivity index for a reasonably effective antiviral drug will be around 10 or 20 or so. A really good antiviral might have a selectivity index of 100 or 200.

But the anti-cytomegalovirus selectivity index for tricin is 1206 ! Ref: 1

So I think tricin would out perform all current cytomegalovirus antivirals.


Unfortunately, I could not find tricin for sale online, except on wholesale websites.

There is far too little tricin in rice bran to have any effect: I calculated that you would need to consume 10 kg of rice bran daily to get a therapeutic dose of tricin.
 

Hip

Well-Known Member
Sugarcane
According to this study, in sugarcane juice, there is around 16 mg of a "tricin derivative" per liter of sugarcane juice.

That's much better than rice bran, which contains only 0.45 mg tricin per kg of rice bran. Ref: 1

But it is not clear whether this tricin derivative will have the same antiviral effects as tricin itself.


In terms of dosing, tricin oral doses of around 7 mg would achieve the EC50 antiviral effect (assuming 100% oral bioavailability).

(This is because the EC50 of tricin for cytomegalovirus is 0.17 μg/ml — ref: here).

But higher doses of tricin would have stronger antiviral effects.

The toxic oral dose of tricin is around 8,200 mg (because the IC50 of tricin is 205 μg/ml), so you would want to keep well below that toxic dose, say not going higher than a 200 mg oral dose of tricin.

So oral doses for tricin would be in the range 7 mg to 200 mg.


Since sugarcane juice has 16 mg of tricin derivative per liter, perhaps the smallest amount of sugarcane juice you could drink in order to get a reasonable antiviral effect against cytomegalovirus would be around half a liter of juice.

Note though that sugarcane juice contains 2690 kilocalories per liter, and the daily intake of kilocalories for a normal person is around 2000 kilocalories.
 
Last edited:

Strike me lucky

Well-Known Member
The flavonoid compound tricin (found in rice bran) has the most extraordinarily potent antiviral effect against cytomegalovirus.

The antiviral potency of a compound is usually measured in terms of its selectivity index (also called the therapeutic index). The selectivity index for a reasonably effective antiviral drug will be around 10 or 20 or so. A really good antiviral might have a selectivity index of 100 or 200.

But the anti-cytomegalovirus selectivity index for tricin is 1206 ! Ref: 1

So I think tricin would out perform all current cytomegalovirus antivirals.


Unfortunately, I could not find tricin for sale online, except on wholesale websites.

There is far too little tricin in rice bran to have any effect: I calculated that you would need to consume 10 kg of rice bran daily to get a therapeutic dose of tricin.

gamma oryzanol/freulic acid is a product of rice bran oil. Plenty of hits on google about it and antiviral properties but i cant find anything specific to cmv, but i didnt look to hard.

I just mention this as its been a supplement for along time, so easily available. Initially its purpose were its anabolic properties and anti inflammatory effects.

Interesting if theres any good research on gamma oryzanol on viruses.
 

Hip

Well-Known Member
gamma oryzanol/freulic acid is a product of rice bran oil. Plenty of hits on google about it and antiviral properties but i cant find anything specific to cmv, but i didnt look to hard.
I couldn't find very much on Google about ferulic acid antiviral effects. But if you look at the selectivity index for typical herbal antivirals, you see figures of around 10, 20 or 30. Tricin's antiviral efficacy is off the scale at 1206.
 

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