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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Women are at a higher risk of dying from heart disease − in part because doctors don’t take major sex and gender differences into account
Heart disease impacts women differently than men due to genetic and gender biases in healthcare. Awareness and improved treatment approaches are essential for better outcomes.
Last Updated on April 20, 2026 by Daily News Staff
Amy Huebschmann, University of Colorado Anschutz Medical Campus and Judith Regensteiner, University of Colorado Anschutz Medical Campus
A simple difference in the genetic code – two X chromosomes versus one X chromosome and one Y chromosome – can lead to major differences in heart disease. It turns out that these genetic differences influence more than just sex organs and sex assigned at birth – they fundamentally alter the way cardiovascular disease develops and presents.
While sex influences the mechanisms behind how cardiovascular disease develops, gender plays a role in how healthcare providers recognize and manage it. Sex refers to biological characteristics such as genetics, hormones, anatomy and physiology, while gender refers to social, psychological, and cultural constructs. Women are more likely to die after a first heart attack or stroke than men. Women are also more likely to have additional or different heart attack symptoms that go beyond chest pain, such as nausea, jaw pain, dizziness and fatigue. It is often difficult to fully disentangle the influences of sex on cardiovascular disease outcomes versus the influences of gender.
While women who haven’t entered menopause have a lower risk of cardiovascular disease than men, their cardiovascular risk accelerates dramatically after menopause. In addition, if a woman has Type 2 diabetes, her risk of heart attack accelerates to be equivalent to that of men, even if the woman with diabetes has not yet gone through menopause. Further data is needed to better understand differences in cardiovascular disease risk among nonbinary and transgender patients.
Despite these differences, one key thing is the same: Heart attack, stroke and other forms of cardiovascular disease are the leading cause of death for all people, regardless of sex or gender.
We are researchers who study women’s health and the way cardiovascular disease develops and presents differently in women and men. Our work has identified a crucial need to update medical guidelines with more sex-specific approaches to diagnosis and treatment in order to improve health outcomes for all.
Gender differences in heart disease
The reasons behind sex and gender differences in cardiovascular disease are not completely known. Nor are the distinct biological effects of sex, such as hormonal and genetic factors, versus gender, such as social, cultural and psychological factors, clearly differentiated.
What researchers do know is that the accumulated evidence of what good heart care should look like for women compared with men has as many holes in it as Swiss cheese. Medical evidence for treating cardiovascular disease often comes from trials that excluded women, since women for the most part weren’t included in scientific research until the NIH Revitalization Act of 1993. For example, current guidelines to treat cardiovascular risk factors such as high blood pressure are based primarily on data from men. This is despite evidence that differences in the way that cardiovascular disease develops leads women to experience cardiovascular disease differently.
In addition to sex differences, implicit gender biases among providers and gendered social norms among patients lead clinicians to underestimate the risk of cardiac events in women compared with men. These biases play a role in why women are more likely than men to die from cardiac events. For example, for patients with symptoms that are borderline for cardiovascular disease, clinicians tend to be more aggressive in ordering artery imaging for men than for women. One study linked this tendency to order less aggressive tests for women partly to a gender bias that men are more open than women to taking risks.
In a study of about 3,000 patients with a recent heart attack, women were less likely than men to think that their heart attack symptoms were due to a heart condition. Additionally, most women do not know that cardiovascular disease is the No. 1 cause of death among women. Overall, women’s misperceptions of their own risk may hold them back from getting a doctor to check out possible symptoms of a heart attack or stroke.
These issues are further exacerbated for women of color. Lack of access to health care and additional challenges drive health disparities among underrepresented racial and ethnic minority populations.
Sex difference in heart disease
Cardiovascular disease physically looks different for women and men, specifically in the plaque buildup on artery walls that contributes to illness.
Women have fewer cholesterol crystals and fewer calcium deposits in their artery plaque than men do. Physiological differences in the smallest blood vessels feeding the heart also play a role in cardiovascular outcomes.
Women are more likely than men to have cardiovascular disease that presents as multiple narrowed arteries that are not fully “clogged,” resulting in chest pain because blood flow can’t ratchet up enough to meet higher oxygen demands with exercise, much like a low-flow showerhead. When chest pain presents in this way, doctors call this condition ischemia and no obstructive coronary arteries. In comparison, men are more likely to have a “clogged” artery in a concentrated area that can be opened up with a stent or with cardiac bypass surgery. Options for multiple narrowed arteries have lagged behind treatment options for typical “clogged” arteries, which puts women at a disadvantage.
In addition, in the early stages of a heart attack, the levels of blood markers that indicate damage to the heart are lower in women than in men. This can lead to more missed diagnoses of coronary artery disease in women compared with men.
The reasons for these differences are not fully clear. Some potential factors include differences in artery plaque composition that make men’s plaque more likely to rupture or burst and women’s plaque more likely to erode. Women also have lower heart mass and smaller arteries than men even after taking body size into consideration.
Reducing sex disparities
Too often, women with symptoms of cardiovascular disease are sent away from doctor’s offices because of gender biases that “women don’t get heart disease.”
Considering how symptoms of cardiovascular disease vary by sex and gender could help doctors better care for all patients.
One way that the rubber is meeting the road is with regard to better approaches to diagnosing heart attacks for women and men. Specifically, when diagnosing heart attacks, using sex-specific cutoffs for blood tests that measure heart damage – called high-sensitivity troponin tests – can improve their accuracy, decreasing missed diagnoses, or false negatives, in women while also decreasing overdiagnoses, or false positives, in men.
Our research laboratory’s leaders, collaborators and other internationally recognized research colleagues – some of whom partner with our Ludeman Family Center for Women’s Health Research on the University of Colorado Anschutz Medical Campus – will continue this important work to close this gap between the sexes in health care. Research in this field is critical to shine a light on ways clinicians can better address sex-specific symptoms and to bring forward more tailored treatments.
The Biden administration’s recent executive order to advance women’s health research is paving the way for research to go beyond just understanding what causes sex differences in cardiovascular disease. Developing and testing right-sized approaches to care for each patient can help achieve better health for all.
Amy Huebschmann, Professor of Medicine, University of Colorado Anschutz Medical Campus and Judith Regensteiner, Professor of Medicine, University of Colorado Anschutz Medical Campus
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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.
(Feature Impact) Shingles isn’t just a painful rash and nerve pain. It’s also linked with a higher risk of serious cardiovascular events, including heart attack and stroke, especially in the weeks to months after infection. However, shingles is largely preventable with vaccination.
The world’s leading nonprofit organization focused on changing the future of health for all, the American Heart Association, reminds eligible adults to protect themselves by getting vaccinated and staying on top of their heart health.
According to the Centers for Disease Control and Prevention (CDC), about 1 in 3 adults in the U.S. will get shingles in their lifetime. If you’ve had chickenpox, the virus that causes shingles, also known as herpes zoster, is already inside you. It can “wake up” years later, causing painful blisters and nerve pain that can last for months or longer.
After a shingles episode, one large study published in the “Journal of the American Heart Association” found the risk of heart attack and stroke was nearly 30% higher in the short term and may persist over time.
“Shingles can be very painful and knock you down for weeks,” said Eduardo Sanchez, M.D., FAHA, the American Heart Association’s chief medical officer for prevention. “It’s also associated with a higher chance of heart and stroke problems afterward. If you’re 50 or older, or have a weakened immune system, talk to your doctor or pharmacist about the shingles vaccine. It’s a simple step that can keep you healthier.”
Knowing your risk is the first step toward prevention. Age is the most important risk factor for developing shingles. As people age, their immune systems naturally weaken, making it easier for the virus to reactivate. People over 50, and especially those living with heart disease, diabetes or other chronic illnesses, are more likely to develop shingles.
The risk of serious complications from shingles increases:
- As you get older
- If you take drugs that keep your immune system from working properly, like steroids and drugs given after an organ transplant
- If you have medical conditions that keep your immune system from working properly such as certain cancers like leukemia and lymphoma, or HIV infection
Heart Health Made Simpler
In addition to ensuring you’re up to date on your vaccines, talk to your health care professional about ways you can improve your overall heart health. According to the American Heart Association, heart disease remains the leading cause of death, taking more lives in the United States than any other cause.
Following healthy lifestyle guidance like Life’s Essential 8 can make inroads toward preventing heart disease and stroke, and improving brain health. The 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) are key measures for improving and maintaining cardiovascular health.
How to Get the Shingles Vaccine
- Check eligibility: Recommended by the CDC for adults 50-plus and adults 19 and older with weakened immune systems.
- Find a location: Most national pharmacies, many primary care and specialty clinics and local health departments offer it. Search your pharmacy’s app or website, or call your clinician’s office.
- Book it: Make an appointment online or by phone. Same‑day or walk‑in options may be available at pharmacies.
- Bring what you need: Photo ID, insurance card and a list of medicines and allergies. Wear a short‑sleeve shirt, if you can.
- Plan for two doses, 2-6 months apart: When you schedule dose one, set a reminder or book dose two before you leave.
- Cost and coverage: Many health plans, including Medicare Part D, cover shingles vaccination at low or no cost. Check your benefits or ask the pharmacy to verify coverage.
- After your shot: A sore arm, fatigue, headache or mild fever are common and usually go away in 2-3 days. Call your clinician about severe or persistent symptoms.
- If you’ve had shingles before: You can still get vaccinated after you recover. Ask your health care provider about timing.
Learn more at heart.org/shingles.
Signs and Symptoms of Shingles
Symptoms to watch for: tingling, itching or burning on one side of the body or face; a stripe‑like rash that turns into fluid‑filled blisters; headache; fever; or chills.
Act fast: If you think you have shingles, contact your health care professional right away. Treatment works best within 72 hours of the rash appearing. If the rash is near your eye or you have eye pain or changes in vision, seek urgent care.
Lasting impact: The rash typically scabs over and clears within 2-4 weeks, but the pain in the rash area can last about a month. The duration of pain seems to increase with age.
Protect Yourself (and Others) from Shingles
If you have shingles, you can stop the spread by covering the rash and avoiding touching or scratching it. You should also wash your hands often, for at least 20 seconds, and avoid contact with people who may be at heightened risk until your rash scabs over, including:
- Pregnant women who never had chickenpox or the chickenpox vaccine
- Premature or low-birthweight infants
- People with weakened immune systems
Photos courtesy of Shutterstock
SOURCE:
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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Cannabis Legalization Drives Innovation, Raises Health Concerns
Cannabis legalization is driving innovation, but much of it focuses on commercial products rather than patient health. New research highlights gaps between market growth and medical evidence.
Lucy Xiaolu Wang, UMass Amherst and Nathan W. Chan, UMass Amherst
Cannabis legalization
Innovation in health care saves lives. But not all health innovations have enough evidence to actually benefit patients.
Barriers to innovation are often higher in illicit or restricted markets, including cannabis, stem cells and cryptocurrencies. Researchers face higher costs, limited access to raw materials and data, and stricter regulations.
Cannabis illustrates a particularly confusing tension between regulatory restrictions on one hand and research and innovation on the other.
While the U.S. federal government still classifies cannabis as having “no accepted medical use,” many states have legalized it for medical or recreational use. Meanwhile, the Department of Health and Human Services obtained a cannabis-related patent in 2003 covering potential medical uses of cannabis compounds for protecting the brain from damage or degeneration. The patent was exclusively licensed for commercialization.
Research and innovation on cannabis can take many forms. Clinical trials may study cannabis products as medical treatments, the effects of cannabis on its users, or factors related to abuse and dependence. Meanwhile, cannabis-related patents can be filed for wide-ranging purposes, such as chemical formulations, methods for production or new consumer products like edibles, beverages or vaporizers.
But do these innovations actually benefit consumers and patients?
We are economists studying how institutional changes affect innovation in different markets. Our recently published research found that legalization of recreational cannabis use appears to spur innovation, but primarily in ways that expand commercial opportunities rather than scientific understanding or health benefits for patients.
Cannabis’ evolving legality in the US
Cannabis is a plant that contains chemical compounds called cannabinoids. One such compound, tetrahydrocannabinol, or THC, produces psychoactive effects, while another compound called cannabidiol, or CBD, is often used to relieve anxiety and pain. However, there has been insufficient evidence on how effective cannabis products are in treating medical conditions, as well as a lack of consistent medical and dosing guidance.
At the federal level in the U.S., cannabis has been classified as a Schedule I drug for over a half-century. This classification indicates that the federal government considers cannabis to have a high potential for abuse and no accepted medical use.
As a Schedule I drug, there are significant restrictions on cannabis research. Researchers who seek to conduct cannabis-related clinical trials must obtain approval from both the Food and Drug Administration and the Drug Enforcement Administration, a process that can take over a year. They are also limited to using select varieties of cannabis obtained from federally authorized cannabis suppliers, and are generally prohibited from studying products available in state-authorized markets.
There are ongoing pushes to relax these restrictions. Meanwhile, cannabis has been legalized to varying extents in many states. California became the first state to pass a medical cannabis law in 1996, allowing qualified patients to grow, possess and use cannabis for medical purposes. Many states followed suit in the late 1990s and early 2000s. As of June 2025, 40 states allow medical cannabis use.
A number of states also allow recreational or nonmedical cannabis use among adults, which is regulated in similar ways to alcohol. Colorado and Washington enacted the first recreational cannabis laws in 2012, and there are 24 states that permit adults to use cannabis recreationally as of January 2026.
Altogether, the legal landscape for cannabis in the U.S. has varied considerably across states and over time. States with more permissive laws can lower the costs of medical research and product development with cannabis, even if federal drug scheduling continues to restrict access. For instance, one group of Washington State University researchers asked participants to independently purchase and smoke cannabis from a legal dispensary before returning to their lab for study.
State legalization and cannabis innovation
To systematically examine how state legalization affects cannabis-related innovation, we compiled and analyzed datasets tracking cannabis-related clinical trials and patent applications.
We distinguished different types of cannabis-related innovation. Specifically, we categorized cannabis-related clinical trials based on whether they focused on its potential as a treatment, its usage and effects, or its role in drug abuse. Similarly, we categorized cannabis-related patents based on whether they focused on chemical compounds, medical uses, methods or products.
We also assessed public health concerns across three measures: patents explicitly involving THC; patents with a high risk of misuse; and patents targeting consumers directly, such as high-potency formulations, edibles or vaporizers.
Then, we compared changes in cannabis-related innovation over time in states that legalized cannabis earlier with those in states that did so later or not at all. We measured innovation by counting the number of cannabis-related clinical trials and patent filings. We distinguished between medical and recreational legalization to assess how different policies affect innovation.
Overall, we found that when states legalize cannabis for recreational use, cannabis-related patents increase – but mostly in commercial-oriented areas rather than health-focused ones. Patents were concentrated in market-oriented innovations like cultivation equipment and consumer products, rather than in clinical or science-based research. We also found some evidence that these innovations may raise public health concerns.
Legalization did not result in meaningful increases in clinical trials. This suggests that barriers to cannabis-related clinical research – such as limited access to research-grade cannabis, limited funding and stigma around working with a federally controlled substance – remain substantial.
Gaps between research and product
As 420 – signifying April 20, a day celebrating cannabis culture – approaches each year, public attention turns toward the legal status of cannabis.
The legal landscape has evolved rapidly over the past few decades, and further changes are in the pipeline. Both the Biden and second Trump administrations have made efforts to reclassify cannabis as a Schedule III substance, which would indicate that it has an accepted medical use and low-to-moderate potential for dependence.
These reevaluations of the legality of cannabis come at a critical time. There has been an explosion of recreational cannabis products in recent years, including increasingly potent strains and a wider variety of ways to use cannabis. Meanwhile, critical research on the health and safety of cannabis use has lagged due to heavy restrictions accompanying Schedule I status.
This gap between medical research and product innovation can have significant public health consequences. The 2019 to 2020 outbreak of lung injuries related to e-cigarette or vape use was linked partly to the use of unregulated or illicit cannabis vaping products. These harms highlight the risks of allowing product innovation for controlled substances to outpace scientific understanding.
Policies that significantly reduce obstacles to clinical research can in turn help close the widening gap between cannabis markets and addressing their public health implications.
Lucy Xiaolu Wang, Assistant Professor of Resource Economics, UMass Amherst and Nathan W. Chan, Professor of Resource Economics, UMass Amherst
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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