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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(Feature Impact) Nothing looks, feels or functions quite like your natural teeth. They’re designed to last a lifetime and, when properly cared for, they often do. Even in the event of an infection or disease that requires additional care, most Americans agree their natural teeth are worth protecting.
In fact, a survey commissioned by the American Association of Endodontists found 61% of Americans would prefer a treatment that saves their natural tooth and about 78% would do almost anything to avoid losing one.
Despite this strong preference, many people delay or avoid dental care altogether. Financial concerns frequently disrupt dental care, with 60% of survey respondents admitting they’ve put off going to the dentist even when they suspected something was wrong. However, postponing care can turn a manageable problem into a more serious one.
When facing dental problems, like severe tooth pain or infection, some may consider removing the tooth as a quick fix. Extraction isn’t always the best solution, though, and can have lasting consequences on both oral health and confidence.
“When possible, you should always consider treatments to save your teeth,” said Dr. Craig Noblett, president, American Association of Endodontists. “You may think, ‘why not have a tooth pulled, especially if no one can see it,’ but you will know your tooth is missing and it will negatively impact your quality of life. Missing teeth can cause other teeth to shift, affecting your ability to properly chew and ruin your smile.”
Another option exists: root canal treatment. While survey data reveals 39% of people are equally concerned about the procedure and losing a natural tooth, 33% worry more about the procedure itself. However, advancements in technology and anesthesia have made root canals – dental procedures to remove inflamed or infected pulp inside the tooth then clean, fill and seal it – are more comfortable than their reputation suggests, similar to getting a routine filling.
To help maintain your smile for the long-term, consider these tips from Noblett to protect your natural teeth and avoid unnecessary tooth loss:
Act immediately when you experience symptoms of swelling or pain. Pain, swelling or sensitivity shouldn’t be ignored. Acting fast is especially critical in urgent situations. For example, fewer than half of Americans (46%) are aware that a knocked-out tooth can often be saved if treated quickly by a dental specialist. Most endodontists can accommodate emergency cases, even on weekends, ensuring you’ll be seen quickly.- Choose root canal treatment instead of extraction when possible. No denture, bridge or implant will look, feel and function as well as a natural tooth. In many cases, extraction is more painful than the infection itself and replacing an extracted tooth with an artificial one requires additional dental visits that can quickly add up. On the other hand, a root canal completed by an endodontist is virtually painless and typically requires less follow up. In fact, patients who experience root canals are six times more likely to describe it as painless compared to those who have a tooth extracted.
- Ask questions about your treatment options. If your dentist recommends tooth extraction, ask whether a root canal is an alternative. A study published in the “Journal of Translational Medicine” suggests that successfully treating tooth infection and inflammation through root canal therapy may support broader health benefits, including improvements in markers related to blood sugar and cholesterol, reducing both the risk of diabetes and heart disease.
- Look for a specialist if needed. If you’re told root canal is not an option, ask why and request a second opinion. Since endodontists can offer solutions dentists cannot, asking for a referral to a local specialist may allow for more advanced care. You can also use the American Association of Endodontists’ Find an Endodontist search tool to find a practice near you.
Learn more about how endodontists can help protect your natural teeth for a lifetime by visiting aae.org/patients.
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American Association of Endodontists
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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(Feature Impact) Whether you’re enjoying a leisurely weekend morning with the family or savoring those last few moments before rushing out the door, a filling, healthy breakfast is a perfect way to begin the day. Easy recipes that take less than 30 minutes (and can even be prepared the night before) make busy mornings a breeze.
Sheet Pan Pancakes are simple to whip up any day of the week – no flipping required – while Healthy Sausage Breakfast Muffins let you put protein on the menu in a kid-friendly package. When shopping for these delicious breakfasts, look for the Healthy Family Project and Produce for Kids logos to choose healthier foods and make a difference locally.
“Breakfast doesn’t have to be complicated to be powerful – a quick, balanced meal can help kids stay full, focused and energized for the day ahead,” said Tony Castillo, contributing registered dietitian at Healthy Family Project. “For growing kids, a protein-rich breakfast can help support energy, satiety and the building blocks they need as they develop. The best breakfast is one that’s simple, satisfying and realistic for busy mornings because consistency matters more than perfection.”
The versatility of these pancakes allows for endless customization and experimentation with different toppings, from fresh fruit and nuts to savory options like cheese and spinach, making them an ideal fit for the whole family. They also freeze well, so you can pop them in the toaster to have breakfast ready in a flash when hectic schedules interfere with your morning routine.
For another on-the-go solution, these breakfast muffins are made with just five ingredients, including protein pancake mix to help fuel the day. The savory combination of turkey sausage and cheddar cheese is complemented by the sweetness of onion, giving them the flavor your family desires.
To find more ways to put a nutritious breakfast on the family table, visit HealthyFamilyProject.com.
Sheet Pan Pancakes
Recipe courtesy of the Healthy Family Project
Prep time: 10 minutes
Cook time: 5 minutes
Servings: 6
- Nonstick cooking spray
- 1 1/2 cups all-purpose flour
- 3 1/2 teaspoons baking powder
- 1 tablespoon sugar
- 1 teaspoon salt
- 1 1/4 cups milk
- 1 large egg
- 2 tablespoons unsalted butter, melted
- 1/2 cup sliced strawberries
- 1/4 cup blueberries
- 1/4 cup mini chocolate chips
- Preheat oven to 425 F. Cover baking sheet with parchment paper and spray with nonstick cooking spray. Set aside.
- In large bowl, mix flour, baking powder, sugar and salt. Add milk, egg and melted butter; mix until smooth.
- Pour batter onto prepared baking sheet and smooth into even layer that covers pan. Top with strawberries, blueberries and chocolate chips.
- Bake 5-7 minutes, or until cooked and golden brown. Let cool slightly before cutting into squares.
Healthy Sausage Breakfast Muffins
Recipe courtesy of the Healthy Family Project
Prep time: 3 minutes
Cook time: 23 minutes
Servings: 12
- Nonstick cooking spray
- 1 onion, diced
- 1 pound turkey sausage
- 4 eggs
- 1/2 cup shredded cheddar cheese
- 1 cup protein pancake mix
- Preheat oven to 350 F.
- Spray 12-cup muffin pan with nonstick cooking spray; set aside.
- Spray large skillet with nonstick cooking spray.
- In prepared skillet over medium heat, cook onion until translucent. Add turkey sausage and cook until no longer pink. Remove from heat.
- In large mixing bowl, lightly beat eggs. Add shredded cheese, pancake mix and sausage and onion mixture; mix well.
- Fill prepared muffin cups about 3/4 full with mixture.
- Bake 18-20 minutes, or until golden brown on top.
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Visit our Food & Drink section to get the latest on Foodie News and recipes, offering a delightful blend of culinary inspiration and gastronomic trends to elevate your dining experience. https://stmdailynews.com/food-and-drink/
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Balance Your Plate with Produce, Protein and Whole Grains
Making health-conscious decisions with your at-home menu doesn’t have to be complicated, but it does require commitment and a little more foresight at the grocery store. Simple adjustments to overall eating patterns, like building your plate around produce, powerful proteins and whole grains, can encourage better health.
(Feature Impact) Making health-conscious decisions with your at-home menu doesn’t have to be complicated, but it does require commitment and a little more foresight at the grocery store. Simple adjustments to overall eating patterns, like building your plate around produce, powerful proteins and whole grains, can encourage better health.
Nutritious meal-planning can be easy, affordable and delicious – and it all starts with a little balance. Consider this advice from the American Heart Association’s Healthy for Good initiative, nationally sponsored by the Egg Nutrition Center, to adequately round out a healthy plate.
Fill Half Your Plate with Fruits and Veggies
Loaded with nutrients, fresh produce is a perfect place to start each plate. Fill about half your plate with combinations of bananas, strawberries, blueberries, sweet potatoes, peas, carrots and more of your favorites. To boost variety with each meal, look for fruit and veggie blends or step out of your usual routine and try something new.
Grocery tip: Frozen fruits and veggies are often cheaper and just as delicious as their fresh counterparts. It’s frozen right after it’s picked, locking in freshness for a longer shelf life. Just be sure to avoid products with added salt or sugar.
Carve Out a Quarter of the Plate for Powerful Proteins
Healthy food isn’t just fuel. It should be easy and nourish you, too. Look for versatile solutions that provide a protein power-up like skinless chicken breast, no-salt-added beans, low-sodium tuna, tofu or eggs.
High-quality protein from foods, along with a balanced diet and regular exercise, can help support the muscles in your body. Eggs are an example, along with lean animal protein and some plant-based proteins. According to the American Heart Association’s guidelines, healthy people can include up to one whole egg daily, and up to seven per week, as part of a heart-healthy diet. For older adults with normal cholesterol, two eggs per day is acceptable.
Eggs deliver both protein and choline, nutrients that help support growing brains and bodies, especially early in life. In fact, many Americans don’t get enough choline, a critical nutrient for supporting brain development, memory and mood.
Grocery tip: Stock up on proteins that offer both versatility and affordability, helping you cook multiple meals per week without putting a dent in your wallet. Eggs are a perfect example as they can be used at any meal, not just breakfast – try them in wraps or omelets in the morning, hard-boil them to go with a lunchtime salad or add to a frittata at dinner.
Save a Corner for Whole Grains
Finally, fill that last quarter of the plate with ready-to-go whole grains, many of which provide dietary fiber that can support a healthy heart and healthy digestion. Conversely, most refined grains contain little or no fiber.
Examples of whole grains include barley, brown rice, corn, oatmeal, rolled or steel-cut oats, popcorn, quinoa, sorghum and wild rice, along with products labeled “whole grain” or “whole wheat” like bread or pasta.
Grocery tip: Look for whole grains that can make mealtime a cinch. Corn tortillas, instant oats and even popcorn can help you create nutritious plates and better-for-you snacks with the snap of your fingers. Try keeping packets of pre-cooked brown rice on hand to bulk up favorite dishes or toss with leftovers to round out a healthy plate.
Visit Heart.org to discover more nutrition guidance for heart-healthy meals.
3 Tips to Complement a Healthy, Balanced Plate
Nutrition isn’t just about what’s on your plate – it’s also about what’s next to it and how much is on it. Pair a balanced meal with this advice to help take healthy eating to the next level.
Stay Hydrated
If it’s not already a habit, add a glass of water to each meal. Staying hydrated helps your heart pump blood throughout the body, get rid of waste and regulate body temperature. While water is the best source of hydration, water-rich foods like fruits and vegetables can also play a role.
Watch Portion Sizes
Pay attention to suggested servings from your favorite food groups. For example, one slice of whole-grain bread, 1/2 cup of cooked pasta and two ounces of cheese (about the size of a domino) are the suggested serving sizes for these popular foods.
You can serve and eat smaller portions by:
- When cooking at home, offer the proper serving size to each family member then put extra food away for leftovers.
- When dining out, skip appetizers and split your meal with a friend or partner.
- Avoid eating while watching TV or at your computer. It may be harder to control how much you’re eating if you’re not paying full attention.
- Mindfully measure out your snacks – even fruits and veggies – into appropriate portions before serving instead of helping yourself directly from the bag or box.
Limit Salt
While sodium supports vital functions like controlling your body’s fluid balance, excess sodium in your bloodstream pulls water into the blood vessels, increasing the amount of blood inside them and thus increasing blood pressure. More than 70% of the sodium people eat comes from packaged, prepared and restaurant foods due to salt added for flavoring, stabilizing, preserving and reducing bacterial risk, according to the American Heart Association.
Cutting back on sodium can help reduce the rise in blood pressure that occurs as you age, even if you don’t have high blood pressure now. It may also help reduce the risk of heart attack, heart failure, kidney disease and more.
Try cooking more meals at home where you can control sodium intake, flavoring foods with herbs and spices instead of table salt and rinsing canned beans and vegetables to wash away excess sodium.
Photo courtesy of Shutterstock (family preparing meal)
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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.
