University of Georgia Scientists Discover New Active Pharmaceutical Ingredient (API) - A Molecule Called POM-L-BHDU To Treat Varicella Zoster Virus
Thailand Medical News Team Aug 09, 2023 1 year, 3 months, 2 weeks, 1 day, 21 hours, 36 minutes ago
Pharma News: You've probably seen the unsettling commercial that warns that the virus responsible for shingles might already be lurking within you if you had chickenpox as a child. This chilling message serves as a reminder for people to consider getting the shingles vaccine. But, alas, the vaccine doesn't provide foolproof protection against shingles; it simply helps mitigate the symptoms.
Addressing this gap, researchers from the University of Georgia (UGA)-USA, Dr David Chu and Dr Uma Singh, have pioneered a novel molecule, named POM-L-BHDU, which holds promise as a potential treatment for the varicella zoster virus. This virus is responsible for both chickenpox and shingles, types of herpes infections.
POM-l-BHDU is the phosphate ester prodrugs of the molecule β-l-5-((E)-2-bromovinyl)-1-((2S,4S)-2-(hydroxymethyl)-1,3-(dioxolane-4-yl) uracil or l-BHDU.
In a groundbreaking study, the study team demonstrated that POM-L-BHDU effectively targets and treats the uncomfortable lesions associated with shingles. Furthermore, the molecule exhibits potential efficacy against oral and genital herpes viruses, which are notoriously challenging to treat due to increasing drug resistance among existing medications.
Lead author, Dr Uma Singh, a lecturer in UGA's College of Pharmacy, emphasized the urgent need for new antiviral molecules, given the growing problem of drug-resistant viruses. She told
Pharma News reporters, "Many viruses are becoming drug-resistant to the current medications on the market. There is a continuous need for new molecules, and the one we developed, called POM-L-BHDU, shows much more potency against the virus than current ones."
Varicella zoster virus (VZV), is an alphaherpesvirus that causes chickenpox (varicella) on primary infection and shingles (zoster) upon reactivation from latency.
At present, vaccination is available with a live attenuated strain for both stages of VZV disease, and an adjuvant subunit vaccine is approved to prevent shingles. Although pediatric vaccination has reduced the incidence of chickenpox, shingles remains prevalent.
According to the U.S. Centers for Disease Control and Prevention, there are an estimated one million cases of zoster annually in the United States. Those at highest risk are individuals over the age of 50, transplant recipients, people living with human immunodeficiency virus (HIV), and anyone who is immunocompromised.
When VZV reactivates in the skin, it causes a painful, vesicular rash that contains abundant infectious virus. Antiviral therapy is most effective when given within three days of the appearance of the rash, and there is evidence that prompt antiviral treatment can reduce acute pain, speed healing, reduce virus shedding, and lower the incidence of herpetic neuropathic pain. A major complication of shingles is postherpetic neuralgia, which is a neuropathic pain that persists for months to years after the rash heals. There is a compelling need for improved antivirals for the treatment of VZV infections that are more effective and safe.
One notable advantage of POM-L-BHDU is its demonstrated safety for use in
treating varicella zoster virus infections in cancer patients, a population that is often more vulnerable due to compromised immune systems. Moreover, this versatile molecule can be administered in various ways, including orally, intravenously, or even topically. The latter application opens up the possibility of developing cream-based medications for both shingles and other herpes outbreaks, providing patients with a convenient and accessible treatment option.
The current landscape for treating herpes and shingles viruses is marred by limited effectiveness and potential life-threatening side effects associated with existing drugs.
Currently, several nucleoside analogues are used to treat VZV infections, including acyclovir (ACV), valacyclovir (VACV), and famciclovir (FCV) These nucleoside analogues act on the viral DNA polymerase to disrupt viral DNA synthesis. They are active in their triphosphate form, requiring the VZV thymidine kinase (TK) and cellular enzymes for activation. These drugs are not highly effective against VZV, large doses are required, and long-term use is associated with the development of drug resistance.
Cidofovir, a commonly used antiviral, can lead to kidney failure in severe cases. In this context, POM-L-BHDU's localized and targeted approach could offer a more effective solution with reduced risk of systemic side effects.
The study also found that POM-l-BHDU L-BHDU had not only good anti-VZV activity but was not cytotoxic.
The researchers envision a broad-spectrum application for POM-L-BHDU, targeting varicella zoster virus as well as herpes simplex 1 and 2 viruses, offering patients the flexibility to choose the most suitable form of administration.
The study team is optimistic about the molecule's potential and aims to propel it into phase 1 clinical trials in the coming years.
Dr Uma Singh expressed her enthusiasm for advancing this project on a larger scale, "We want to push this project as soon as possible into large-scale synthesis. It has the potential to benefit society on a large scale."
The University of Georgia Research Foundation has already licensed the molecule to a pharmaceutical company named Anterogen Co., underscoring the tangible progress toward making this innovative treatment option widely available.
The study findings were published in the peer reviewed Journal of Medicinal Chemistry.
https://pubs.acs.org/doi/10.1021/acs.jmedchem.3c00545#
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