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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Consumer Corner
Cold cities are the most ready for winter, with one exception. See where your city ranks
Cold cities? Every neighborhood has a mix of homeowners who approach seasonal home maintenance differently – there are the people who stay on schedule, and on the other end, the procrastinators. There are the dedicated DIYers, and those who have their favorite maintenance pro saved as a favorite contact in their phone. As it turns out, cities are no different. Some metropolitan areas keep their neighborhoods in tip-top shape, while others are a little more slow-going.
Cold cities are the most ready for winter, with one exception. See where your city ranks
(Sheeka Sanahori) Every neighborhood has a mix of homeowners who approach seasonal home maintenance differently – there are the people who stay on schedule, and on the other end, the procrastinators. There are the dedicated DIYers, and those who have their favorite maintenance pro saved as a favorite contact in their phone. As it turns out, cities are no different. Some metropolitan areas keep their neighborhoods in tip-top shape, while others are a little more slow-going.
New data from home services company Angi, covering fall maintenance activity in August, reveals which U.S. metropolitan areas are the most proactive with fall maintenance. Washington, D.C., tops the ranking with the strongest demand for fall maintenance in the country, followed by Columbus, Ohio, and Milwaukee, Wisconsin. Northern cities dominate the rest of the list.
Cleveland, Ohio, and Albany-Schenectady-Troy, New York, round out the top five. Cold-weather markets dominate the ranking, accounting for eight of the 10 most-prepared metros. Rochester, New York; Charlotte, North Carolina; Chicago; Indianapolis; and Pittsburgh complete the top 10.
Least fall-ready metros
Fewer than 1 in 5 American cities is prepping for fall at an above-average rate. Among the 66 metros that recorded at least 100 fall maintenance service requests during the analysis period, Los Angeles had the lowest level of per-capita activity, followed by Oklahoma City and Riverside, California. California accounts for four of the bottom 10 markets, with Los Angeles, Riverside, San Diego and San Francisco all appearing on the list. These metros historically don’t experience the colder winter climates of the Northeast and Midwest, making fall maintenance less of an imperative.
Grand Rapids, Michigan, stands out as the only clearly cold-weather metro among the 10 least-prepared large metros. The New York City metro, which includes Newark and Jersey City, ranked just outside the 10 least-prepared large metros, coming in at number 11. Other New York state metros, including Syracuse, Rochester and the Albany metro area, were on the most prepared list.
Homeowners are choosing upkeep over upgrades
Sixty-three percent of homeowners who have recently hired a professional completed maintenance work, and 58% completed repairs. Although they may be waiting to do that dream kitchen or bath renovation, they’re focusing for now on the maintenance that keeps their homes in order.
The most common fall maintenance projects focus on outdoor upkeep. Nationally, tree trimming was the most popular, followed by lawn and yard waste cleanup and shrub care.
What homeowners should do now
When tackling a home maintenance list, start at the top of the home by inspecting the roof and gutters. Look for loose or damaged shingles, and make sure gutters are debris-free. It’s also a good idea to ensure downspouts direct water far away from the foundation. Homeowners should inspect these areas from the ground or hire a professional if the work requires climbing or feels unsafe.
Next, check for drafts around the windows and doors. Replacing worn weatherstripping and damaged caulk in the fall can prevent warm air from escaping once the heat comes back on. Homeowners should also inspect their HVAC filters and have the heating system checked before the temperatures drop.
Every home’s maintenance needs will vary, depending on the age and condition of the house and where it’s located. Whether homeowners hire a professional or safely address small issues, making the fixes can prevent larger and more expensive problems later.
The ranking: Metros from most to least prepared
America’s 10 Most Fall-Prepared Metros
1. Washington, D.C.
2. Columbus, Ohio
3. Milwaukee, Wisconsin
4. Cleveland, Ohio
5. Albany-Schenectady-Troy, New York
6. Rochester, New York
7. Charlotte, North Carolina
8. Chicago, Illinois
9. Indianapolis, Indiana
10. Pittsburgh, Pennsylvania
10 Metros With the Most Opportunity to Get Fall-Ready
1. Los Angeles, California
2. Oklahoma City, Oklahoma
3. Riverside, California
4. Miami, Florida
5. San Diego, California
6. Houston, Texas
7. Grand Rapids, Michigan
8. San Francisco, California
9. Austin, Texas
10. Memphis, Tennessee
Methodology
The rankings are based on fall maintenance activity recorded on Angi during August 2026. Projects included yard cleanup, winterization, roofing and gutters, heating systems, water and drainage, outdoor plumbing, fireplaces and chimneys, pest prevention, and snow and storm preparation. U.S. metropolitan areas were ranked by activity per 100,000 residents using 2020 U.S. Census population data. To qualify for the least-prepared ranking, metros were required to have at least five service requests or jobs during the analysis period. The rankings reflect activity on Angi’s platform and are not a complete measure of all home-maintenance activity within each metro. These rankings reflect activity observed on Angi’s platform and should not be interpreted as a complete measure of all home-maintenance behavior within a metro area.
Photo courtesy of Shutterstock
SOURCE:
Angi
Health
Type 2 Diabetes Doesn’t Have to Be Your Future: Medicare Has a Benefit That Can Help
Left unchecked, prediabetes can progress to type 2 diabetes. However, with the right support, prediabetes can often be managed or even reversed. If you have Medicare, you may qualify for a Medicare-covered program that can help you lower your chances of developing type 2 diabetes – at no cost to you.
(Feature Impact) Nearly 1 in 2 people age 65 and older has prediabetes – a condition where blood sugar (glucose) levels run higher than normal. Left unchecked, prediabetes can progress to type 2 diabetes. However, with the right support, prediabetes can often be managed or even reversed. If you have Medicare, you may qualify for a Medicare-covered program that can help you lower your chances of developing type 2 diabetes – at no cost to you.
The Medicare Diabetes Prevention Program is a covered Medicare benefit that gives you practical tools, personalized support, and proven strategies to make healthy lifestyle changes. Learn how to eat better, exercise more, and build healthy habits that stick while guided by a certified coach who helps you every step of the way.
Research shows the program works. People with prediabetes who complete the program result in weight loss, which ultimately leads to reduced risk of type 2 diabetes onset.
What can you expect?
Prevention does not mean you have to make big changes all at once. This program helps you take small, realistic steps that can add up to lasting results. It includes 16 core sessions where you can learn how to reduce your diabetes risk by making healthier meals, moving more, and building healthy habits.
The core sessions are followed by six months of monthly maintenance sessions to help you keep your momentum.
You can choose the class format that works for you
You can enroll in these services from approved Medicare Diabetes Prevention Program suppliers and participate in the way most convenient for you:
- In-Person: Attend sessions in a community location.
- Live-Distance Learning: Join interactive group sessions from home.
- Self-Paced Online: This new option allows you to access online content and learn on your own schedule.
Visit www.medicare.gov/PreventDiabetes to find a class that’s right for you.
Who is eligible?
You may qualify if you are enrolled in Medicare Part B and meet these criteria:
- Have had one of the following test results within the past 12 months:
- Hemoglobin A1c between 5.7% and 6.4%
- Fasting plasma glucose between 110 and 125 mg/dL
- Two-hour plasma glucose between 140 and 199 mg/dL after an oral glucose tolerance test
- Have a body mass index (BMI) of 25 or higher (or 23 or higher if you self-report as Asian descent).
- Have never been diagnosed with type 1 or type 2 diabetes or end-stage renal disease (ESRD).
What does it cost?
If you have Medicare Part B and qualify for the program, you pay nothing to participate. If you are in a Medicare Advantage Plan, you may have to go to an in-network provider to get these services. Contact your plan for more information.
Ready to get started on your healthier future?
Take control of your health on your own terms, schedule, and pace that fits into your life. Check with your doctor to find out if you have prediabetes or are at risk for developing type 2 diabetes. If you’re eligible for the Medicare Diabetes Prevention Program, your doctor can refer you, or you can enroll on your own.
If you’re ready to get started today, find the class that’s right for you at: www.medicare.gov/PreventDiabetes.
Information provided by the U.S. Department of Health and Human Services
Photos courtesy of Shutterstock
SOURCE:
Centers for Medicare & Medicaid Services
health and wellness
The Oral and Cardiovascular Health Connection: 4 Tips to Protect Your Teeth, Gums and Heart
People often think of dentists and doctors as totally separate healthcare professionals: one cares for your teeth and mouth while the other handles the rest of the body. In reality, the different systems in the human body are closely interconnected and oral health is no exception, making dentists a vital part of your healthcare team. Care for your teeth, gums and heart all at once using these tips.
(Feature Impact) People often think of dentists and doctors as totally separate healthcare professionals: one cares for your teeth and mouth while the other handles the rest of the body. In reality, the different systems in the human body are closely interconnected and oral health is no exception, making dentists a vital part of your healthcare team.
Oral health and heart health have a particularly close connection, with inflammation at the core of it. When your gums are inflamed, the resulting bacteria can make their way from your mouth through your bloodstream, potentially contributing to your blood vessels constricting or becoming blocked. This, in turn, may force your heart to work harder and raise your blood pressure, putting you at risk of heart disease and stroke. More than 46% of adults in the U.S. have high blood pressure, and more than 40% of adults age 30 and older are affected by periodontal (gum) disease.
To help address these issues, the American Heart Association’s Healthy Smiles, Healthy Hearts initiative, in collaboration with Delta Dental of California, is encouraging dental teams to take a total-body perspective with their patients. Simple steps like blood pressure screenings during checkups can give a more complete picture of a person’s overall health. If a member of your dental care team pulls out a blood pressure cuff at your next appointment, it’s a good sign.
“The mouth is a gateway to the body and can often reveal more about your total body health than you may think,” said Daniel Croley, D.M.D., chief dental officer at Delta Dental of California and Affiliates. “Oral health professionals have a powerful opportunity to integrate more into their patients’ collective health care team beyond protecting their patients’ teeth By connecting oral health and heart health, this initiative helps dentists identify risks early and guide patients toward care that can improve and even save lives.”
Care for your teeth, gums and heart all at once using these tips from experts at the American Heart Association.
Follow a Brushing and Flossing Schedule
Good dental health starts with a daily routine. If you don’t want to sheepishly cringe next time the dentist inquires about yours, brush at least twice a day and floss at least once a day to disrupt plaque-forming bacteria. Dentists recommend using toothpaste with fluoride and brushing your teeth and gums thoroughly yet gently, as applying too much pressure can wear away enamel and cause gum recession.
Eat a Healthy Diet and Limit Sugar
Most kids are used to hearing sugar will rot their teeth – and that’s not just a parental scare tactic to get their little hands out of the candy jar. Sugar feeds harmful bacteria in your mouth, producing acid that can cause cavities and gum disease. For a diet your heart and teeth will both appreciate, prioritize vegetables, lean proteins, complex carbohydrates and healthy fats, while limiting added sugars and refined carbohydrates.
Avoid Smoking and Tobacco Products
The connection between smoking and oral disease is well established: smokers face significantly higher risks of developing periodontal disease, losing teeth or being diagnosed with oral cancer. Cigarettes aren’t the only form of tobacco to worry about, either. Vaping, dipping and chewing tobacco can also harm your dental health by drying out your mouth and restricting blood flow to the gums. Since these products are also harmful to heart health, quitting or avoiding them offers plenty of worthwhile benefits. Seek support if you need help to kick the habit.
Communicate with Your Healthcare Team
Since your body’s systems are connected to each other, it’s helpful to talk to your dentist about your blood pressure and to your doctor about your oral health. Start thinking of your dentist as a key member of your integrated healthcare team. Don’t be afraid to share your medical history, discuss the side effects of any medications you’re taking and ask for personalized recommendations on caring for your teeth, gums and overall health.
To learn more about how to improve your oral and cardiovascular health, visit Heart.org/OralHealth.
Photos courtesy of Shutterstock
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