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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health and wellness
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.
Last Updated on March 9, 2026 by Daily News Staff
(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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Food and Beverage
Get Smart About Your Heart: 4 tips to improve heart health
Heart health is essential for overall well-being, particularly as heart disease is a leading cause of death in the U.S. Key strategies include regular checkups, healthy eating—especially fruits like grapes—consistent exercise, and stress management to minimize risks.
Last Updated on March 8, 2026 by Daily News Staff
(Family Features) A crucial component of overall well-being, heart health can be a barometer for living a long, healthy and happy life. Because heart disease is the leading cause of death in the United States, according to the Centers for Disease Control and Prevention, taking steps to reduce your controllable risk factors – including poor diet, stress and inactivity – can set you on the right path.
From regular checkups and reducing stress to eating well – including heart-healthy snacks like grapes – and exercising regularly, these simple steps can help boost your heart health.
Know Your Numbers
Knowing key health metrics such as blood pressure, cholesterol levels, blood sugar levels and body mass index can help you and your health care provider identify potential risks early. Schedule annual checkups and discuss any concerns you may have about your heart health. Early detection and risk factor management can reduce the likelihood of developing heart disease.
Eat More Fruits and Vegetables
Incorporating a variety of colorful fruits and vegetables into your diet can ensure you get a broad range of vitamins, minerals, fiber and antioxidants, all of which contribute to a healthy cardiovascular system. For example, leafy greens like spinach and kale are high in potassium, which helps manage blood pressure. Fresh grapes contain 7% of the daily recommended intake of potassium, are a good source of vitamin K and are also a natural source of beneficial antioxidants and other polyphenols, including flavonoids, that can help relax blood vessels and promote healthy circulation. Some studies also suggest grapes have a beneficial impact on blood lipids and more.
In fact, one study found women who consumed 1 1/4 cups of grapes every day benefited from reduced blood triglyceride levels, LDL cholesterol levels, inflammatory proteins and other markers of heart disease.
Bright, juicy and bursting with flavor, Grapes from California can be enjoyed by the handful or blended with rich bananas, tangy Greek yogurt and a hint of almond in The Great Grape-Acai Smoothie Bowl for a delicious blend of fruity flavors at breakfast, lunch or snack time – it not only tastes great, but supports a healthy heart.
Get Moving
Regular physical activity is one of the most effective ways to improve heart health. Exercise strengthens the heart muscle, improves blood circulation and helps maintain a healthy weight. Aim for at least 150 minutes of moderate-intensity aerobic exercise per week, as recommended by the American Heart Association, such as walking, jogging or swimming with strength training exercises like lifting weights or using resistance bands mixed in to help reduce the risk of heart disease and improve overall cardiovascular health.
Manage Stress
Consider your stress level: chronic stress can negatively impact heart health, increasing blood pressure and other risk factors for heart disease. Techniques such as deep breathing, meditation, yoga and regular physical activity can help manage stress levels and maintain a healthy heart. Additionally, taking time to engage in hobbies, spending time with loved ones and ensuring adequate sleep are stress-reducing activities that improve overall well-being and heart health.
To learn more about the heart-health benefits of grapes, and find additional heart-friendly recipes, visit GrapesFromCalifornia.com.
The Great Grape-Acai Smoothie Bowl
Servings: 1
Chicken:
- 1/2 cup red Grapes from California, fresh or frozen
- 1/2 banana
- 1 frozen acai fruit pack (3 1/2 ounces)
- 1/2 cup plain, nonfat Greek yogurt
- 1/4 teaspoon almond extract
Topping:
- 1/4 cup sliced red Grapes from California
- 1 tablespoon sliced, toasted almonds
- 1 tablespoon pepitas
- 1 teaspoon chia seeds
- In small blender, combine grapes, banana, acai, yogurt and almond extract; process until smooth.
- Pour into bowl and top with sliced grapes, sliced almonds, pepitas and chia seeds.
Nutritional information per serving: 420 calories; 19 g protein; 63 g carbohydrates; 12 g fat (26% calories from fat); 2.5 g saturated fat (5% calories from saturated fat); 5 mg cholesterol; 45 mg sodium; 8 g fiber.
SOURCE:
California Table Grape Commission
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Lifestyle
Understanding Cardiovascular Disease Risk Factors: Numbers to Know in 2026
The American Heart Association’s 2026 update reveals a decrease in deaths from heart disease and stroke, despite rising rates of high blood pressure, diabetes, and obesity. Following their Life’s Essential 8 guidelines can prevent 40% of cardiovascular deaths, emphasizing the importance of healthier lifestyles for improved heart health.
Last Updated on March 4, 2026 by Daily News Staff
Understanding Cardiovascular Disease Risk Factors: Numbers to Know in 2026
(Family Features) Taking care of your heart with healthy behaviors may be at the top of your wellness priority list already, and there may be good news about the effects of adhering to expert recommendations.
New information from the American Heart Association’s 2026 Heart Disease & Stroke Statistics Update shows deaths from heart disease and stroke are on the decline. However, rates continue to climb for high blood pressure, diabetes and obesity – all of which are health risk factors that contribute to cardiovascular disease.
Following expert guidance can be your prescription for better health as 80% of heart disease and stroke is preventable.
To help maintain and improve your cardiovascular health, consider following the American Heart Association’s Life’s Essential 8, which is a set of four health behaviors (eat better, be more active, quit tobacco and get healthy sleep) and four health factors (manage weight, control cholesterol, manage blood sugar and manage blood pressure).
In the United States, optimal Life’s Essential 8 scores could prevent up to 40% of annual all-cause and cardiovascular disease deaths among adults.
Consider these highlights from the statistics update:
- Heart disease remains the leading cause of death in the U.S. and stroke is the No. 4 leading cause of death.
- Together, heart disease and stroke accounted for more than a quarter of all deaths in the U.S. in 2023.
- Cardiovascular diseases, including all types of heart disease and stroke, claim more lives in the U.S. each year than all forms of cancer and accidental deaths — the Nos. 2 and 3 causes of death – combined.
- On average, every 34 seconds, someone died of cardiovascular disease in 2023.
- On average, about two people died of heart disease every 3 minutes in the U.S. in 2023.
- On average in 2023, someone died of stroke every 3 minutes, 14 seconds in the U.S.
- Nearly half of U.S. adults now have high blood pressure.
- Nearly 29.5 million U.S. adults have diagnosed diabetes.
- About 50% of U.S. adults have obesity or severe obesity, and 28.1% of youth ages 2-19 have obesity.
- Only 1 in 4 U.S. adults meets national physical activity guidelines. Only 1 in 5 U.S. youths ages 6-17 are physically active for 60 minutes or more every day of the week.
To learn more about how to reduce your risk of cardiovascular disease, visit heart.org.
Photo courtesy of Shutterstock
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