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
How Young Adults Can Build a Healthier Future
Bridging national service and public health, the initiative supports a diverse group of early career professionals working to address today’s public health challenges in a range of roles
(Family Features) Shaping the future of public health into an equitable one means ensuring all people and communities have access to the health care and resources they need to live well. The nation requires a strong, diverse public health workforce to accomplish that goal.
That’s why AmeriCorps and the Centers for Disease Control and Prevention launched Public Health AmeriCorps – to support the recruitment, training and development of early career public health workers who can serve their local communities.
Bridging national service and public health, the initiative supports a diverse group of early career professionals working to address today’s public health challenges in a range of roles, including:
- Health education and training
- Community outreach and engagement
- System navigation, referrals and linkage to care
- Research, data collection, analysis and assessment
What Members are Saying
Everyone was impacted by the COVID-19 pandemic – including Dionne Johnson, who lost a loved one to the virus.
“I had a family member die from COVID-19, and it really touched me,” Johnson said. “That gave me the passion and lit the fire under me to actually pursue a career in public health.”
Now, Johnson is realizing her dreams of transforming public health in her community. In her work, she wants to teach people in Black and brown communities how they can learn to be healthy and advocate for themselves.
Another member, Jaiden Singh, is the son of immigrants. Singh launched a promising career in public health so he can give back to the community where he grew up.
“Being a part of the organization not only has really supplemented my education that I’m working toward in public health and policy, it has also given me the opportunity to do work that I am really passionate about in a community that I have known all my life and really do love,” Singh said. “I would highly recommend being a part of this really valuable and inspiring community.”
Action That Creates Impact
The diverse work of Public Health AmeriCorps benefits not only program members but also the communities they serve. As examples of the program at work, members have:
- Provided overdose rescue education, raised awareness about opioid use disorder and harm reduction strategies and distributed overdose rescue kits containing naloxone (an overdose-reversing nasal spray).
- Held back-to-school COVID-19 testing events, distributed early childhood health education and built community gardens in underserved communities.
- Participated in a community mental health crisis intervention system to assess, stabilize and link people in crisis to follow-up care and services.
- Supported elementary schools as part of a dental hygiene program that sends out staff and volunteers to provide free teeth cleanings to students.
Learn More and Apply
If you want to start your career and make a difference in public health, consider member benefits such as:
- Education awards to apply to higher education or student loan forgiveness
- Student loan deferment and forbearance
- Living allowance
- Hands-on experience
- Training from experts
Visit AmeriCorps.gov/PublicHealth for a list of opportunities to serve and contact your desired opportunity by phone or email to learn more and apply. You can also subscribe to the newsletter to learn more about the initiative.
SOURCE:
AmeriCorps
Lifestyle
Saving a Life This Summer: Ways to Step Up Safety Practices
Regardless of where you are, summer is a reminder that emergencies like cardiac arrest can happen anywhere. Take the safety of those around you into your own hands this summer with this checklist.
(Feature Impact) The busy summer season can take you almost anywhere – baseball fields, backyard cookouts, long workdays or road trips across the country. Regardless of where you are, summer is a reminder that emergencies like cardiac arrest can happen anywhere.
More than 350,000 out-of-hospital cardiac arrests occur in the United States each year, and 90% of people will not survive, according to the American Heart Association, a nonprofit organization devoted to changing the future for a world of healthier lives for all. Sudden cardiac arrest can happen anytime, anywhere. People often hesitate to step in. In fact, nearly 2 out of 3 adults believe CPR can only be performed by medical professionals. This mistaken belief can cost lives and contributes to the low survival rate.
Ordinary people have extraordinary power. You don’t need to wear scrubs or have a medical background to save a life – you just need the courage to act.
Take the safety of those around you into your own hands this summer with this checklist.
Plan Ahead
Summer is often a time for welcome disruptions, including vacations, camps, sports and parties. Before traveling or attending events, check if your destination has a cardiac emergency response plan, which establishes specific steps to reduce death from cardiac arrest in any setting, from schools and community organizations to workplaces and sports facilities.
Learn CPR
Cardiac arrest can happen anywhere: at home, at work, in schools, at a soccer game or on vacation. When it happens, the first chance for survival often rests with the people nearby.
Anyone can be the difference before professional help arrives. The power to save a life is in your hands. CPR is a human responsibility, not just a medical skill. When friends, family or even strangers step in during cardiac emergencies, survival rates can double or even triple.
Hands-Only CPR for adults consists of two easy steps:
- Call 9-1-1 or shout for someone else to call.
- Push hard and fast in the center of the chest to the beat of a familiar song that’s 100-120 beats per minute, such as “Stayin’ Alive” by the Bee Gees.
Share Resources with Your Family and Community
Once you’ve learned simple, two-step Hands-Only CPR, share resources with your community to help expand the American Heart Association’s Nation of Lifesavers. Raising awareness with family, neighbors and colleagues can help people feel confident in the face of an emergency.
Families can watch short instructional videos that demonstrate the life-saving steps for adults as well as techniques for infants and children.
Travelers can also get trained in about 5 minutes with a Hands-Only CPR Kiosk, located in many airports and public spaces across the country.
To find more information about learning CPR, visit Heart.org/Nation.
Summer Safety Tips
In addition to learning CPR and sharing valuable resources with your family and community, consider these ways to keep yourself and loved ones safe throughout the summer months.
- Stay Hydrated: High temperatures can quickly lead to dehydration and heat-related illness. Drink water regularly throughout the day, especially during outdoor activities, and pack extra water when away from home.
- Protect Your Skin: Hats, sunglasses and lightweight clothing can protect skin from sun exposure, but it’s important to use broad-spectrum sunscreen and reapply every 2 hours.
- Swim with a Buddy: Hopping in a pool, lake or ocean is a hallmark of summer but can be dangerous without precautions. Never swim alone and ensure children are always supervised by an adult near water.
- Identify the Locations of Safety Equipment: When attending camps, heading to a sporting event or enjoying the pool or beach, identify where lifeguards, AEDs and emergency exits are located. Knowing where to find help can save valuable time when every second counts.
- Practice Grill Safety: Some of your most memorable summer moments may happen during a backyard barbecue or cookout, and it’s important to keep those gatherings safe. Use grills away from homes, decks and dry grass. Never leave them unattended while cooking, and be sure kids and pets stay at a safe distance from hot surfaces.
Saving a Life Within 1 Year of Learning CPR
On a chilly Tuesday, dawn was breaking as Matthew Lynch reached his highway exit, but traffic was backed up at a particular intersection. He waited through three cycles before finally getting close enough to see the holdup: a stalled SUV.
While most cars buzzed by, Lynch moved slowly and peered into the vehicle. He saw people inside and parked his sedan, flipped on the hazard lights and ran to the stalled SUV. As he knocked on the driver’s window, there was no response. The doors were locked. Two people – a male driver and female passenger – were unresponsive.
Lynch ran back to his own car and called 9-1-1 before managing to open the driver’s side door. He discovered the driver was not breathing normally, signaling to Lynch he’d need to start CPR – which he’d learned 10 months earlier during a training session he’d helped organize for a work-sponsored men’s group.
Knowing he had to do something, Lynch started pushing hard and fast in the center of the man’s chest. Within a minute, the man gasped for breath.
Just as Lynch leaned over to see if he could help the female passenger, first responders arrived and Lynch backed away, knowing there was nothing more he could do.
“It was just a lot to take in,” said Lynch, a member of the American Heart Association’s 2026 Nation of Lifesavers Class, a small group of volunteers, dedicated to raising awareness of CPR by sharing their own personal stories of survival or rescue. “Mostly I felt an incredible sense of gratitude that I could help someone.”
A strong admirer of the Good Samaritan parable, Lynch is always on the lookout for the opportunity to help others. He learned a lot about himself in that moment and about the importance of learning CPR, along with the confidence that comes from knowing you could be a lifesaver.
“I quickly realized the certification was way less important than the actual CPR training,” he said. “Your ability to help in any capacity is better than doing nothing. If I hadn’t done that training, I probably would not have helped.”
SOURCE:
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News
How healthy is Sodastream?
The SodaStream Sparkling Water Maker is a device that forces carbon dioxide (CO2) gas (stored under pressure in a cylinder) into water, making it sparkling (fizzy)
Sodastream machines have been gaining popularity in recent years as an alternative to store-bought soft drinks. Not only are they more environmentally friendly, but they also offer several health benefits compared to traditional sodas.
Reduced Sugar Intake
One of the most significant health benefits of using a Sodastream machine is reducing sugar intake. Traditional sodas are loaded with sugar, and excessive sugar intake can lead to weight gain, obesity, and other health problems such as Type 2 diabetes. With a Sodastream machine, you can control the amount of sugar you add to your drink, allowing you to enjoy a refreshing beverage without the harmful effects of excessive sugar consumption.
No Artificial Sweeteners
Many store-bought soft drinks contain artificial sweeteners, which can have negative health effects such as headaches and digestive problems. Sodastream machines, on the other hand, allow you to use natural sweeteners such as fruit extracts, honey or agave nectar, giving you a healthier and more natural alternative.
No Preservatives
Another advantage of using a Sodastream machine is that you can avoid preservatives commonly found in store-bought soft drinks. Preservatives such as sodium benzoate and potassium sorbate have been linked to health problems such as cancer and allergies. By making your own drinks, you can avoid these harmful additives and enjoy a healthier, preservative-free beverage.
Eco-Friendly
In addition to the health benefits, using a Sodastream machine is also environmentally friendly. Traditional soft drinks are packaged in plastic bottles or cans, which contribute to environmental pollution. With a Sodastream machine, you can reuse the same bottle multiple times, reducing waste and helping to reduce your carbon footprint.
Variety
Finally, Sodastream machines offer a wide variety of flavors and options, allowing you to customize your drink to your liking. You can mix and match different flavors or create your own unique blends, giving you a healthier and more enjoyable alternative to traditional sodas.
In conclusion, Sodastream machines offer several health benefits compared to traditional store-bought soft drinks. By reducing sugar intake, avoiding artificial sweeteners and preservatives, and being eco-friendly, they offer a healthier and more sustainable alternative to traditional soft drinks. Moreover, with a wide variety of flavors and options, you can customize your drink to your liking, making it a fun and enjoyable way to stay healthy.
