Research pinpoints key to the cold sore virus’s ability to evade treatment, offering broader clues on antiviral drug resistance
A 3D representation of a herpes simplex virus enzyme involved in viral replication.
« What Enables Herpes Simplex Virus To Become Impervious to Drugs?
Credit: Jonathan Abraham Lab/HMS
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
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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.
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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?
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FDA’s COVID-19 Vaccine Safety Claims Lack Solid Evidence—Why Overreaction Could Harm Public Health
COVID-19 vaccine safety: The FDA’s claims about COVID-19 vaccine deaths in children lack strong evidence and could restrict vaccine access. Learn why experts say VAERS reports aren’t proof, and how overreacting may harm public health and trust in vaccines.
The death of children due to an unsafe vaccine is a serious allegation. I am a pediatric cardiologist who has studied the link between COVID-19 vaccines and heart-related side effects such as myocarditis in children. To my knowledge, studies to date have shown such side effects are rare, and severe outcomes even more so. However, I am open to new evidence that could change my mind. But without sufficient justification and solid evidence, restricting access to an approved vaccine and changing well-established procedures for testing vaccines would carry serious consequences. These moves would limit access for patients, create roadblocks for companies and worsen distrust in vaccines and public health. In my view, it’s important for people reading about these FDA actions to understand how the evidence on a vaccine’s safety is generally assessed.
Determining cause of death
The FDA memo claims that the deaths of these children were directly related to receiving a COVID-19 immunization. From my perspective as a clinician, it is awful that any child should die from a routine vaccination. However, health professionals like me owe it to the public to uphold the highest possible standards in investigating why these deaths occurred. If the FDA has evidence demonstrating something that national health agencies worldwide have missed – widespread child deaths due to myocarditis caused by the COVID-19 vaccine – I don’t doubt that even the most pro-vaccine physician will listen. So far, however, no such evidence has been presented. While a death logged in VAERS is a starting point, on its own it is insufficient to conclude whether a vaccine caused the death or other medical causes were to blame. To demonstrate a causal link, FDA staff and physicians must align the VAERS report with physicians’ assessments of the patient, as well as data from other sources for monitoring vaccine safety. These include PRISM, which logs insurance claims data, and the Vaccine Safety Datalink, which tracks safety signals in electronic medical records. It’s known that most deaths logged only in VAERS of children who recently received vaccines have been incorrectly attributed to the vaccines – either by accident or in some cases on purpose by anti-vaccine activists.
Heart-related side effects of COVID-19 vaccines
In his Substack and Twitter accounts, Prasad has said that he believes the rate of severe cardiac side effects after COVID-19 vaccination is severely underestimated and that the vaccines should be restricted far more than they currently are. In a July 2025 presentation, Prasad quoted a risk of 27 cases per million of myocarditis in young men who received the COVID-19 vaccine. A 2024 review suggested that number was a bit lower – about 20 cases out of 1 million people. But that same study found that unvaccinated people had greater risk of heart problems after a COVID-19 infection than vaccinated people. In a different study, people who got myocarditis after a COVID-19 vaccination developed fewer complications than people who got myocarditis after a COVID-19 infection. Existing vaccine safety infrastructure in the U.S. successfully identifies dangers posed by vaccines – and did so during the COVID-19 pandemic. Today, most COVID-19 vaccines in the U.S. rely on mRNA technology. But as vaccines were first emerging during the COVID-19 pandemic, two pharmaceutical companies, Janssen and AstraZeneca, rolled out a vaccine that used a different technology, called a viral vector. This type of vaccine had a very rare but genuine safety problem that was detected.A report in VAERS is at most a first step to determining whether a vaccine caused harm. VAERS, the Vaccine Safety Datalink, clinical investigators in the U.S. and their European counterparts detected that these vaccines did turn out to cause blood clotting. In April 2021, the FDA formally recommended pausing their use, and they were later pulled from the market. Death due to myocarditis from COVID-19 vaccination is exceedingly rare. Demonstrating that it occurred requires proof that the person had myocarditis, evidence that no other reasonable cause of death was present, and the absence of any additional cause of myocarditis. These factors cannot be determined from VAERS data, however – and to date, the FDA has presented no other relevant data.
A problematic vision for future vaccine approvals
Currently, vaccines are tested both by seeing how well they prevent disease and by how well they generate antibodies, which are the molecules that help your body fight viruses and bacteria. Some vaccines, such as the COVID-19 vaccine and the influenza vaccine, need to be updated based on new strains. The FDA generally approves these updates based on how well the new versions generate antibodies. Since the previous generation of vaccines was already shown to prevent infection, if the new version can generate antibodies like the previous one, researchers assume its ability to prevent infection is comparable too. Later studies can then test how well the vaccines prevent severe disease and hospitalization. The FDA memo says this approach is insufficient and instead argues for replacing such studies with many more placebo-controlled trials – not just for COVID-19 vaccines but also for widely used influenza and pneumonia vaccines. That may seem reasonable theoretically. In practice, however, it is not realistic. Today’s influenza vaccines must be changed every season to reflect mutations to the virus. If the FDA were to require new placebo-controlled trials every year, the vaccine being tested would become obsolete by the time it is approved. This would be a massive waste of time and resources.Influenza vaccines must be updated for every flu season.Jacob Wackerhausen/iStock via Getty Images Plus Also, detecting vaccine-related myocarditis at the low rate at which it occurs would have required clinical trials many times larger than the ones that were done to approve COVID-19 mRNA vaccines. This would have cost at least millions of dollars more, and the delay in rolling out vaccines would have also cost lives. Placebo-controlled trials would require comparing people who receive the updated vaccine with people who remain unvaccinated. When an older version of the vaccine is already available, this means purposefully asking people to forgo that vaccine and risk infection for the sake of the trial, a practice that is widely considered unethical. Current scientific practice is that only a brand-new vaccine may be compared against placebo. While suspected vaccine deaths should absolutely be investigated, stopping a vaccine for insufficient reasons can lead to a significant drop in public confidence. That’s why it’s essential to thoroughly and transparently investigate any claims that a vaccine causes harm.
PFAS in pregnant women’s drinking water puts their babies at higher risk, study finds
A new study shows pregnant women exposed to PFAS-contaminated drinking water face higher risks of low birth weight, preterm birth, and infant mortality. Learn how PFAS, or “forever chemicals,” impact babies and what you can do to reduce exposure.
PFAS, or perfluoroalkyl and polyfluoroalkyl substances, have captured the attention of the public and regulators in recent years for good reason. These man-made compounds persist in the environment, accumulate in human bodies and may cause harm even at extremely low concentrations. Most current knowledge about the reproductive effects of PFAS comes from laboratory studies on animals such as rats, or from correlations between PFAS levels in human blood and health outcomes. Both approaches have important limitations. Rats and humans have different bodies, exposures and living conditions. And independent factors, such as kidney functioning, may in some cases be the true drivers of health problems. We wanted to learn about the effects of PFAS on real-world human lives in a way that comes as close as possible to a randomized experiment. Intentionally exposing people to PFAS would be unethical, but the environment gave us a natural experiment of its own. We looked at the locations of wells that supply New Hampshire residents with drinking water and how those locations related to birth outcomes. We collected data on all births in the state from 2010 to 2019 and zoomed in on the 11,539 births that occurred within 3.1 miles (5 kilometers) of a site known to be contaminated with PFAS and where the mothers were served by public water systems. Some contamination came from industries, other from landfills or firefighting activities.A conceptual illustration shows how PFAS can enter the soil and eventually reach groundwater, which flows downhill. Industries and airports are common sources of PFAS. The homes show upstream (left) and downstream (right) wells.Melina Lew PFAS from contaminated sites slowly migrate down through soil into groundwater, where they move downstream with the groundwater’s flow. This created a simple but powerful contrast: pregnant women whose homes received water from wells that were downstream, in groundwater terms, from the PFAS source were likely to have been exposed to PFAS from the contaminated site, but those who received water from wells that were upstream of those sites should not have been exposed. Using outside data on PFAS testing, we confirmed that PFAS levels were indeed greater in “downstream” wells than in “upstream” wells. The locations of utilities’ drinking water wells are sensitive data that are not publicly available, so the women likely would not have known whether they were exposed. Prior to the state beginning to test for PFAS in 2016, they may not have even known the nearby site had PFAS.
PFAS connections to the riskiest births
We found what we believe is clear evidence of harm from PFAS exposure. Women who received water from wells downstream of PFAS-contaminated sites had on average a 43% greater chance of having a low-weight baby, defined as under 5.5 pounds (2,500 grams) at birth, than those receiving water from upstream wells with no other PFAS sources nearby. Those downstream had a 20% greater chance of a preterm birth, defined as before 37 weeks, and a 191% greater chance of the infant not surviving its first year. Per 100,000 births, this works out to 2,639 additional low-weight births, 1,475 additional preterm births and 611 additional deaths in the first year of life. Looking at the cases with the lowest birth weights and earliest preterm births, we found that the women receiving water from wells downstream from PFAS sources had a 180% greater chance of a birth under 2.2 pounds (1,000 grams) and a 168% greater chance of a birth before 28 weeks than those with upstream wells. Per 100,000 births, that’s about 607 additional extremely low-weight births and 466 additional extremely preterm births.
PFAS contamination is costly
When considering regulations to control PFAS, it helps to express the benefits of PFAS cleanup in monetary terms to compare them to the costs of cleanup. Researchers use various methods to put a dollar value on the cost of low-weight and preterm births based on their higher medical bills, lower subsequent health and decreased lifetime earnings. We used the New Hampshire data and locations of PFAS-contaminated sites in 11 other states with detailed PFAS testing to estimate costs from PFAS exposure nationwide related to low birth weight, preterm births and infant mortality. The results are eye-opening. We estimate that the effects of PFAS on each year’s low-weight births cost society about US$7.8 billion over the lifetimes of those babies, with more babies born every year. We found the effects of PFAS on preterm births and infant mortality cost the U.S. about $5.6 billion over the lifetimes of those babies born each year, with some of these costs overlapping with the costs associated with low-weight births. An analysis produced for the American Water Works Association estimated that removing PFAS from drinking water to meet the EPA’s PFAS limits would cost utilities alone $3.8 billion on an annual basis. These costs could ultimately fall on water customers, but the broader public also bears much of the cost of harm to fetuses. We believe that just the reproductive health benefits of protecting water systems from PFAS contamination could justify the EPA’s rule.
Treating PFAS
There is still much to learn about the risks from PFAS and how to avoid harm. We studied the health effects of PFOA and PFOS, two “long-chain” species of PFAS that were the most widely used types in the U.S. They are no longer produced in the U.S., but they are still present in soil and groundwater. Future work could focus on newer, “short-chain” PFAS, which may have different health impacts.If the water utility isn’t filtering for PFAS, or if that information isn’t known, people can purchase home water system filters to remove PFAS before it reaches the faucet.Compassionate Eye Foundation/David Oxberry via Getty ImagesPFAS are in many types of products, and there are many routes for exposure, including through food. Effective treatment to remove PFAS from water is an area of ongoing research, but the long-chain PFAS we studied can be removed from water with activated carbon filters, either at the utility level or inside one’s home. Our results indicate that pregnant women have special reason to be concerned about exposure to long-chain PFAS through drinking water. If pregnant women suspect their drinking water may contain PFAS, we believe they should strongly consider installing water filters that can remove PFAS and then replacing those filters on a regular schedule. Derek Lemoine, Professor of Economics, University of Arizona; Ashley Langer, Professor of Economics, University of Arizona, and Bo Guo, Associate Professor of Hydrology, University of Arizona This article is republished from The Conversation under a Creative Commons license. Read the original article.
The science section of our news blog STM Daily News provides readers with captivating and up-to-date information on the latest scientific discoveries, breakthroughs, and innovations across various fields. We offer engaging and accessible content, ensuring that readers with different levels of scientific knowledge can stay informed. Whether it’s exploring advancements in medicine, astronomy, technology, or environmental sciences, our science section strives to shed light on the intriguing world of scientific exploration and its profound impact on our daily lives. From thought-provoking articles to informative interviews with experts in the field, STM Daily News Science offers a harmonious blend of factual reporting, analysis, and exploration, making it a go-to source for science enthusiasts and curious minds alike. https://stmdailynews.com/category/science/
Empowering Seniors for Safer Online Experiences: 6 Practical Safety Tips for Caregivers and Families
Safety Tips for Caregivers: Empower seniors with essential online safety tips. Learn 6 practical strategies caregivers can use to help older adults navigate digital threats, scams, and security risks confidently.
Empowering Seniors for Safer Online Experiences: 6 Practical Safety Tips for Caregivers and Families
(Family Features) Today’s seniors aren’t shying away from a world that has become increasingly reliant on technology. Quite the opposite, in fact, as recent survey findings suggest adults ages 65 and older are more digitally active and self-assured than ever before. Nearly all seniors surveyed as part of the “Connecting the Digital Dots: Online Habits and Safety Concerns Across Three Generations” survey from Cox Mobile consider themselves digitally literate, using devices for shopping, banking, social media and entertainment. With older adults spending a significant amount of time connected to the digital world – 41% of those surveyed reported spending five or more hours online daily – they’re also more at-risk for scams, viruses like malware and data breaches. Even though 61% of seniors who encountered digital threats were able to mitigate the issues themselves, showing their growing digital capability, increased online engagement brings new challenges and responsibilities for caregivers, who often play a crucial role in supporting seniors’ digital journeys. To help support older loved ones’ safety and confidence as they navigate an evolving digital landscape, Cox Mobile, in partnership with Common Sense Media, offers educational materials on digital safety, smart device use and media literacy for all ages. In addition, these practical safety strategies can help empower seniors to make informed, safe choices online. Encourage Strong Passwords: Simple passwords, like number sequences, keyboard patterns or personal information – such as variations of your name, birthdate, address or names of pets or loved ones – are easily guessable and may lead to issues. While the survey found 70% of seniors already create strong, unique passwords, encourage them to avoid reusing passwords across sites. Recommend a password manager app to safely store passwords and eliminate the need to write them all down, which could lead to a breach if not stored properly. Promote Security Software: If devices aren’t protected, even the most careful users are susceptible to viruses. Though 63% of those surveyed have security software installed, it’s important to regularly make sure it’s up to date (or that automatic updates are enabled) and covers all devices, including laptops, tablets and smartphones. Enable Multi-Factor Authentication: A simple and effective way to stop most attempts at unauthorized account access, 60% of seniors are already using multi-factor authentication as an extra layer of protection. Some seniors, however, may need assistance setting up the safeguard, which typically sends a code to a phone number or email address as part of the login process, for online banking, email or social media accounts. Review Apps and Channels: Over time, it can be easy to accumulate apps on smartphones and tablets. While 51% of surveyed seniors remove unsafe apps, make it a habit to regularly check loved ones’ devices for unfamiliar or suspicious applications and delete them. Also keep an eye out for unauthorized charges, data sharing or browser extensions. Utilize Built-In Safety Features: Explore privacy controls on individual devices (and apps) and check with your loved ones’ internet service provider to ensure security features are being utilized like the 43% of those surveyed who are already taking advantage of their devices’ safety settings. Included privacy protections may include limiting data sharing, disabling location tracking, blocking pop-ups and restricting other unwanted communication. Discuss Online Safety Regularly: Because technology is ever-changing, it’s important for caregivers to talk with senior loved ones about online safety. Open, ongoing conversations, like those one-third of seniors are already having several times a week or even daily, can help build trust and awareness of current scams, suspicious texts or emails, commonly used apps and more. By fostering open dialogue, sharing practical safety strategies and leveraging trusted resources, caregivers can help their loved ones thrive and stay safe. Visit your local Cox Mobile store or go to CoxMobileSafety.com to find more tips, guides and full survey results. SOURCE:Cox Communications
Promote Security Software: If devices aren’t protected, even the most careful users are susceptible to viruses. Though 63% of those surveyed have security software installed, it’s important to regularly make sure it’s up to date (or that automatic updates are enabled) and covers all devices, including laptops, tablets and smartphones. Enable Multi-Factor Authentication: A simple and effective way to stop most attempts at unauthorized account access, 60% of seniors are already using multi-factor authentication as an extra layer of protection. Some seniors, however, may need assistance setting up the safeguard, which typically sends a code to a phone number or email address as part of the login process, for online banking, email or social media accounts. Review Apps and Channels: Over time, it can be easy to accumulate apps on smartphones and tablets. While 51% of surveyed seniors remove unsafe apps, make it a habit to regularly check loved ones’ devices for unfamiliar or suspicious applications and delete them. Also keep an eye out for unauthorized charges, data sharing or browser extensions. Utilize Built-In Safety Features: Explore privacy controls on individual devices (and apps) and check with your loved ones’ internet service provider to ensure security features are being utilized like the 43% of those surveyed who are already taking advantage of their devices’ safety settings. Included privacy protections may include limiting data sharing, disabling location tracking, blocking pop-ups and restricting other unwanted communication. Discuss Online Safety Regularly: Because technology is ever-changing, it’s important for caregivers to talk with senior loved ones about online safety. Open, ongoing conversations, like those one-third of seniors are already having several times a week or even daily, can help build trust and awareness of current scams, suspicious texts or emails, commonly used apps and more. By fostering open dialogue, sharing practical safety strategies and leveraging trusted resources, caregivers can help their loved ones thrive and stay safe. Visit your local Cox Mobile store or go to 
