Health
What Enables Herpes Simplex Virus To Become Impervious to Drugs?
Research pinpoints key to the cold sore virus’s ability to evade treatment, offering broader clues on antiviral drug resistance
Newswise — All organisms — from fungi to mammals — have the capacity to evolve and adapt to their environments. But viruses are master shapeshifters with an ability to mutate greater than any other organism. As a result, they can evade treatments or acquire resistance to once-effective antiviral medications.
Is the Herpes Simplex Virus Becoming Impervious to Drugs?
Working with herpes simplex virus (HSV), a new study led by Harvard Medical School researchers sheds light on one of the ways in which the virus becomes resistant to treatment, a problem that could be particularly challenging among people with compromised immune function, including those receiving immune-suppressive treatment and those born with immune deficiencies.
Using a sophisticated imaging technique called cryogenic electron microscopy (cryo-EM), the researchers found that how parts of a protein responsible for viral replication move into different positions can alter the virus’s susceptibility to medicines.
The findings, published Aug. 27 in Cell, answer long-standing questions about why certain viruses, but not others, are susceptible to antiviral medications and how viruses become impervious to drugs. The results could inform new approaches that impede viruses’ capacity to outpace effective therapies.
Counterintuitive results
Researchers have long known changes that occur on the parts of a virus where antiviral drugs bind to it can render it resistant to therapy. However, the HMS researchers found that, much to their surprise, this was often not the case with HSV.
Instead, the investigators discovered that protein mutations linked to drug resistance often arise far from the drug’s target location. These mutations involve alterations that change the movements of a viral protein, or enzyme, that allows the virus to replicate itself. This raises the possibility that using drugs to block or freeze the conformational changes of these viral proteins could be a successful strategy for overcoming drug resistance.
“Our findings show that we have to think beyond targeting the typical drug-binding sites,” said the study’s senior author, Jonathan Abraham, associate professor of microbiology in the Blavatnik Institute at HMS and infectious disease specialist at Brigham and Women’s Hospital. “This really helps us see drug resistance in a new light.”
The new findings propel the understanding of how alterations in the conformation of a viral protein — or changes in how the different parts within that protein move when it carries out its function — fuel drug resistance and may be relevant for understanding drug effectiveness and drug resistance in other viruses, the researchers noted.
HSV, estimated to affect billions of people worldwide, is most commonly known as the cause of cold sores and fever blisters, but it can also lead to serious eye infections, brain inflammation, and liver damage in people with compromised immunity. Additionally, HSV can be transmitted from mother to baby via the birth canal during delivery and cause life-threatening neonatal infections.
Clues on resistance rooted in structure and movement
A virus can’t replicate on its own. To do so, viruses must enter a host cell, where they unleash their replication tools — proteins called polymerases — to make copies of themselves.
The current study focused on one such protein — a viral DNA polymerase — crucial for HSV’s ability to reproduce and propagate itself. The ability to carry out its function is rooted in the DNA polymerase’s structure, often likened to a hand with three parts: the palm, the thumb, and the fingers, each carrying out critical functions.
Given their role in enabling replication, these polymerases are critical targets of antiviral drugs, which aim to stop the virus from reproducing itself and halt the spread of infection. The HSV polymerase is the target of acyclovir, the leading antiviral drug for treating HSV infection, and of foscarnet, a second-line drug used for drug-resistant infections. Both drugs work by targeting the viral polymerase but do so in different ways.
Scientists have long struggled to fully understand how alterations in the polymerase render the virus impervious to normal doses of antiviral drugs and, more broadly, why acyclovir and foscarnet are not always effective against the altered forms of the HSV polymerase.
“Over the years, the structures of many polymerases from various organisms have been determined, but we still don’t fully understand what makes some polymerases, but not others, susceptible to certain drugs,” Abraham said. “Our study reveals that how the different parts of the polymerases move, known as their conformational dynamics, is a critical component of their relative susceptibility to drugs.”
Proteins, including polymerases, are not rigid, motionless objects. Instead, they are flexible and dynamic.Composed of amino acids, they initially fold into a steady, three‐dimensional shape known as the native conformation — their baseline structure. But as a result of various bonding and dispersing forces, the different parts of proteins can move when they come into contact with other cellular components as well as through external influences, such as changes in pH or temperature. For example, the fingers of a polymerase protein can open and close, as would the fingers of a hand.
Conformational dynamics — the ability of different parts of a protein to move — allow them to efficiently administer many essential functions with a limited number of ingredients. A better understanding of polymerase conformational dynamics is the missing link between structures and functions, including whether a protein responds to a drug and whether it could become resistant to it down the road.
Unraveling the mystery
Many structural studies have captured DNA polymerases in various distinct conformations. However, a detailed understanding of the impact of polymerase conformational dynamics on drug resistance is lacking. To solve the puzzle, the researchers carried out a series of experiments, focusing on two common polymerase conformations — an open one and a closed one — to determine how each affects drug susceptibility.
First, using cryo-EM, they conducted structural analysis to get high-resolution visualizations of the atomic structures of HSV polymerase in multiple conformations, as well as when bound to the antiviral drugs acyclovir and foscarnet. The drug-bound structures revealed how the two drugs selectively bind polymerases that more readily adopt one conformation versus another. One of the drugs, foscarnet, works by trapping the fingers of the DNA polymerase so that they are stuck in a so-called closed configuration.
Further, structural analysis paired with computational simulations suggested that several mutations that are distant from the sites of drug binding confer antiviral resistance by altering the position of the polymerase fingers responsible for closing onto the drug to halt DNA replication.
The finding was an unexpected twist. Up until now, scientists have believed that polymerases closed partially only when they attached to DNA and closed fully only when they added a DNA building block, a deoxynucleotide. It turns out, however, that HSV polymerase can fully close just by being near DNA. This makes it easier for acyclovir and foscarnet to latch on and stop the polymerase from working, thus halting viral replication.
“I’ve worked on HSV polymerase and acyclovir resistance for 45 years. Back then I thought that resistance mutations would help us understand how the polymerase recognizes features of the natural molecules that the drugs mimic,” said study co-author Donald Coen, professor of biological chemistry and molecular pharmacology at HMS. “I’m delighted that this work shows that I was wrong and finally gives us at least one clear reason why HSV polymerase is selectively inhibited by the drug.”
Authorship, funding, disclosures
Additional authors included Sundaresh Shankar, Junhua Pan, Pan Yang, Yuemin Bian, Gábor Oroszlán, Zishuo Yu, Purba Mukherjee, David J. Filman, James M. Hogle, Mrinal Shekhar.
This work was supported by the National Institutes of Health (awards R21 AI141940 and R01 AI19838), with additional funding from a Centers for Integrated Solutions in Infectious Diseases grant.
What Enables Herpes Simplex Virus To Become Impervious to Drugs?
Source: Harvard Medical School
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Study Links Agent Orange Exposure to Higher Risk of Rare Melanoma
A study revealed that U.S. veterans exposed to Agent Orange are at increased risk of developing acral melanoma, a rare skin cancer located in areas not typically exposed to sunlight. With higher odds of diagnosis and poorer prognosis, early detection in veterans is vital for effective treatment and improved outcomes.
(Feature Impact) A new study found U.S. veterans exposed to Agent Orange face a higher risk of developing a rare and often overlooked form of melanoma that appears on the hands and feet, and under the nails.
Researchers reported in “JAMA Dermatology” that veterans with documented exposure to the herbicide had significantly higher odds of developing acral melanoma, a subtype of skin cancer that forms on the palms, soles and nail beds.
Unlike most melanomas, which are associated with ultraviolet radiation, acral melanoma develops in areas not typically exposed to the sun. It can resemble a bruise under a toenail or a dark patch on the bottom of a foot – locations that are easily missed and not commonly associated with skin cancer.
Because of its unusual appearance and location, acral melanoma is often diagnosed at later stages, when treatment is more difficult and survival rates are lower.
The researchers analyzed 20 years of Veterans Health Administration data, comparing more than 1,200 veterans diagnosed with acral melanoma with more than 5,000 veterans without melanoma. Veterans exposed to Agent Orange had about 30% higher odds of developing the disease.
The findings suggest Agent Orange may be an underrecognized risk factor for acral melanoma, particularly for veterans who may not view themselves as at risk for skin cancer because of limited sun exposure or darker skin tones.
“Identifying exposures that may increase risk can help inform earlier recognition and, ultimately, earlier diagnosis when treatment is most effective,” said Marc Hurlbert, chief executive officer of the Melanoma Research Alliance and a principal investigator on the study.
Senior author Dr. Rebecca I. Hartman of Brigham and Women’s Hospital said acral melanoma behaves differently from other melanomas and often responds less well to current therapies.
“Acral melanoma has a poorer prognosis than the more common cutaneous melanoma because it is often diagnosed at later stages,” Hartman said. “Identifying risk factors is critical to improving detection and outcomes.”
Agent Orange was used extensively during the Vietnam War and exposure has been linked to several cancers and chronic illnesses. These findings add to evidence the herbicide may also affect the skin in ways not reflected in traditional melanoma awareness efforts.
Acral melanoma has also been associated with sex, race and ethnicity, and prior skin lesions. Researchers said the study supports treating the disease as distinct from sun-driven melanomas that dominate public education campaigns.
For veterans, the research highlights the importance of examining less visible areas of the body, including the bottoms of the feet, between the toes and under the nails. Changes in nail color, dark streaks or unexplained spots on the palms or soles should be evaluated by a health care provider, especially for those with known Agent Orange exposure.
Researchers said the findings could help guide future screening strategies for higher-risk populations and encourage further study of why acral melanoma differs biologically from other skin cancers.
Find more information at curemelanoma.org.
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Progress, Not Perfection: How Healthy Habits Can Stack Up One Step at a Time
The article emphasizes that achieving better health relies on progress, not perfection. It advocates for realistic goals and highlights tools like My Life Check for personalized health assessments. Small, manageable changes in diet, exercise, sleep, and stress management can significantly impact overall well-being, making healthy habits more attainable and sustainable.
Progress, Not Perfection: How Healthy Habits Can Stack Up One Step at a Time
(Feature Impact) Despite the best of intentions, it’s common for plans to build healthier habits to fall flat. Often, the culprit isn’t a lack of motivation or discipline; rather, it’s unrealistic expectations.
Overhauling your lifestyle requires a level of commitment that isn’t always practical. Understanding your personal health needs and the challenges you need to overcome can help give you a more realistic roadmap toward better health.
Tools to Guide You
Every plan needs a starting point and there are many reputable sources that can help guide you toward a plan that addresses your personal health needs.
For example, the American Heart Association introduced My Life Check, a simple, free tool to help individuals understand their heart health and what’s driving it. Users answer simple questions about their daily habits and health factors to get a personalized Heart Health Score in minutes.
The results are private and downloadable, giving you full control of your information. The tool turns big goals into small, specific actions you can start right away. Knowing your numbers relative to your heart health (and where you are in comparison to target ranges for optimal health) can help you decide how to build a better map to get you where you want to be.
While the report is customized to each individual, no personal data is stored and answers are only used to calculate health scores and provide personalized recommendations and practical steps to improve your health, so you can use your results to focus on what matters most to you. Every small step you take, such as moving more, eating smarter, sleeping better or managing stress, can add up over time.
Finding Your Path
Once you’re armed with data and know where you stand on your heart health numbers, small steps become clearer and more manageable. That knowledge makes it easier to choose one area to focus on, such as getting more sleep, taking daily walks or adding more color to your meals.
Healthy changes don’t need to be expensive or complicated. The best habits are ones that fit real life when every action you take moves you closer to your goals.
Staying motivated and on track is also easier when you can check back in, see your progress and realize the steps you’re taking are making an impact. Checking in every few months to see how you can grow gives you the chance to celebrate your progress, learn from challenges and keep building lasting habits that feel good.
To get started with personalized tips to set your own health goals, visit heart.org/mylifecheck.
Healthy Habits for Everyday Life
Eat Smart
Choose foods that help you feel your best, one meal at a time. Add more color to your plate and focus on balance, not restriction. Simple, affordable swaps can make a real difference.
Smart Tip: Aim for an overall healthy eating pattern that includes whole foods, fruits and vegetables, lean protein, nuts, seeds and cooking in non-tropical oils such as olive and canola.
Move More
Find movement that fits your life, such as a walk, a stretch or dancing while you cook. Every bit of activity counts and it all supports your heart and mind. Move for joy, not just for results.
Smart Tip:Adults should get 150 minutes of moderate physical activity (or 75 minutes of vigorous activity) per week. Kids should aim for 60 minutes every day, including play and structured activities.
Sleep Well
Rest is a foundation of good health, not a reward. Protect your bedtime routine and give your body the recovery it deserves. Notice how good sleep makes everything else easier.
Smart Tip: Most adults need 7-9 hours of sleep each night. Children require more. Adequate sleep promotes healing, improves brain function and reduces the risk for chronic diseases.
Manage Stress
Check in with yourself regularly, both mentally and emotionally. Create simple moments to pause, breathe, laugh or step outside. Connection, kindness and calm all support a healthy heart.
Smart Tip:The first step to stress management is awareness. Step “away from yourself” for a moment. Objectively ask yourself, “Is my stress level too high?” If so, look at what might be causing that stress.
Ideas for Incremental Changes
- Dedicate 15 minutes at the beginning or end of the day to focus on self-care, whether it’s unwinding with some music, writing down your goals or reflecting on the highlights of the day.
- Aim to add an extra serving of fruits or veggies each day, such as creating a savory veggie omelet or exploring new smoothie blends that let you pack in the produce on the go.
- Give your cabinets a quick update and put the smaller plates front and center. When you use a smaller plate, you can fill it while still sticking to recommended serving sizes.
- If you’re not a fan of the gym, think about how your hobbies can play a role in your physical activity. Even gardening counts as physical activity, so get creative to get moving with an activity you truly enjoy.
- Establish a bedtime routine that allows you to ease into sleep more easily. Once you feel the impact of better-quality rest, you may find yourself more motivated to make a regular bedtime a priority.
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4 Tips to Maximize Nutritional Goals While On a GLP-1
GLP-1 medications for weight loss have gained popularity, with new research emphasizing the importance of nutrition and lifestyle. Prioritizing protein and fiber can combat common side effects like nausea and constipation, while staying hydrated and eating smaller meals enhances tolerance. Adopting these habits may improve weight loss results for GLP-1 users.
(Feature Impact) The first GLP-1 (Glucagon-Like Peptide-1) medication was approved for weight loss use more than a decade ago with new more effective versions being approved by the FDA over the past few years. As the use of these medications continues to rise, new research highlights the important role nutrition and lifestyle habits can play in supporting muscle, metabolism and long-term weight loss when using the medication.
Whether you’re new to GLP‑1s or navigating the next phase of your journey, small nutrition shifts powered by protein, fiber and hydration can help you feel strong, confident and supported.
Common side effects experienced by GLP-1 users are often digestive and include nausea, constipation, stomach pain, bloating and more. A pilot clinical trial by Atkins suggests pairing GLP‑1 use with targeted macronutrients, especially protein and fiber, may support healthier body composition and a lower-carb diet with higher protein and fiber intake is well tolerated.
Feast On Fiber
Digestive slow‑downs, including constipation, are among the most common GLP‑1 side effects. Prioritizing fiber not only helps food move comfortably through the body, it supports your gut health and steady energy. Many fibers are prebiotics, meaning they promote the growth of beneficial gut bacteria. Prioritize foods like apples, melon, berries, cruciferous vegetables and leafy greens to boost fiber intake.
Prioritize Protein
When your appetite changes, structure helps. Anchoring your day with reliable protein sources helps make nutrition easy. Prioritizing protein may help prevent lean muscle loss, and nutrient dense protein sources can help you get enough essential nutrients to support overall health. Supporting a protein- and fiber-rich diet can start with a solution like Atkins High Protein Shakes, which are packed with 30 grams of protein and 7 grams of prebiotic fiber and provide more than 20 essential vitamins and minerals.
Designed to be an ally for your nutritional goals, they’re gluten-free, low-glycemic and keto-friendly with 3 grams of net carbs and 1 gram of sugar per serving. Experts recommend making sure you’re consuming enough protein to help limit lean muscle loss when using a GLP-1 to lose weight.
Hydrate to Help Prevent Side Effects
GLP-1 users in particular are encouraged to prioritize fluids. Staying hydrated can help with both constipation and nausea, two common side effects. Drinking water helps support kidney and liver function, which are vital for weight loss and overall health. Adequate fluids help food move through your body, combat fatigue and replenish losses from potential nausea or constipation, preventing complications and improving tolerance to GLP-1s.
Eat Small, Frequent Meals
Large meals can feel uncomfortable when digestion slows. Instead, focus on smaller, more frequent eating moments that give your body a steady supply of nutrients without overwhelming your system.
For an easy, GLP‑1‑friendly option, try Atkins High Protein Bars, which are high in protein and fiber while minimizing net carbs. Available in flavors like Cookie Fusion, Chocolate Peanut Butter and Brownie Delight, they’re a satisfying way to stay fueled between meals and a simple solution when appetite cues are muted. The snacks are designed to take the guesswork out of choosing high‑protein, low‑carb options that support your goals.
Living well on a GLP‑1 is about support, confidence and clarity. Consuming adequate amounts of protein and fiber, staying hydrated and maintaining daily structure can help you feel energized and empowered every step of the way. By following nutritional guidelines and making mindful lifestyle choices, GLP-1 users can experience better outcomes on their weight loss journeys.
To explore products that prioritize protein and fiber that can be a part of anyone’s daily diet, visit Atkins.com.
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Our Lifestyle section on STM Daily News is a hub of inspiration and practical information, offering a range of articles that touch on various aspects of daily life. From tips on family finances to guides for maintaining health and wellness, we strive to empower our readers with knowledge and resources to enhance their lifestyles. Whether you’re seeking outdoor activity ideas, fashion trends, or travel recommendations, our lifestyle section has got you covered. Visit us today at https://stmdailynews.com/category/lifestyle/ and embark on a journey of discovery and self-improvement.
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