Health
What Enables Herpes Simplex Virus To Become Impervious to Drugs?
Research pinpoints key to the cold sore virus’s ability to evade treatment, offering broader clues on antiviral drug resistance
Newswise — All organisms — from fungi to mammals — have the capacity to evolve and adapt to their environments. But viruses are master shapeshifters with an ability to mutate greater than any other organism. As a result, they can evade treatments or acquire resistance to once-effective antiviral medications.
Is the Herpes Simplex Virus Becoming Impervious to Drugs?
Working with herpes simplex virus (HSV), a new study led by Harvard Medical School researchers sheds light on one of the ways in which the virus becomes resistant to treatment, a problem that could be particularly challenging among people with compromised immune function, including those receiving immune-suppressive treatment and those born with immune deficiencies.
Using a sophisticated imaging technique called cryogenic electron microscopy (cryo-EM), the researchers found that how parts of a protein responsible for viral replication move into different positions can alter the virus’s susceptibility to medicines.
The findings, published Aug. 27 in Cell, answer long-standing questions about why certain viruses, but not others, are susceptible to antiviral medications and how viruses become impervious to drugs. The results could inform new approaches that impede viruses’ capacity to outpace effective therapies.
Counterintuitive results
Researchers have long known changes that occur on the parts of a virus where antiviral drugs bind to it can render it resistant to therapy. However, the HMS researchers found that, much to their surprise, this was often not the case with HSV.
Instead, the investigators discovered that protein mutations linked to drug resistance often arise far from the drug’s target location. These mutations involve alterations that change the movements of a viral protein, or enzyme, that allows the virus to replicate itself. This raises the possibility that using drugs to block or freeze the conformational changes of these viral proteins could be a successful strategy for overcoming drug resistance.
“Our findings show that we have to think beyond targeting the typical drug-binding sites,” said the study’s senior author, Jonathan Abraham, associate professor of microbiology in the Blavatnik Institute at HMS and infectious disease specialist at Brigham and Women’s Hospital. “This really helps us see drug resistance in a new light.”
The new findings propel the understanding of how alterations in the conformation of a viral protein — or changes in how the different parts within that protein move when it carries out its function — fuel drug resistance and may be relevant for understanding drug effectiveness and drug resistance in other viruses, the researchers noted.
HSV, estimated to affect billions of people worldwide, is most commonly known as the cause of cold sores and fever blisters, but it can also lead to serious eye infections, brain inflammation, and liver damage in people with compromised immunity. Additionally, HSV can be transmitted from mother to baby via the birth canal during delivery and cause life-threatening neonatal infections.
Clues on resistance rooted in structure and movement
A virus can’t replicate on its own. To do so, viruses must enter a host cell, where they unleash their replication tools — proteins called polymerases — to make copies of themselves.
The current study focused on one such protein — a viral DNA polymerase — crucial for HSV’s ability to reproduce and propagate itself. The ability to carry out its function is rooted in the DNA polymerase’s structure, often likened to a hand with three parts: the palm, the thumb, and the fingers, each carrying out critical functions.
Given their role in enabling replication, these polymerases are critical targets of antiviral drugs, which aim to stop the virus from reproducing itself and halt the spread of infection. The HSV polymerase is the target of acyclovir, the leading antiviral drug for treating HSV infection, and of foscarnet, a second-line drug used for drug-resistant infections. Both drugs work by targeting the viral polymerase but do so in different ways.
Scientists have long struggled to fully understand how alterations in the polymerase render the virus impervious to normal doses of antiviral drugs and, more broadly, why acyclovir and foscarnet are not always effective against the altered forms of the HSV polymerase.
“Over the years, the structures of many polymerases from various organisms have been determined, but we still don’t fully understand what makes some polymerases, but not others, susceptible to certain drugs,” Abraham said. “Our study reveals that how the different parts of the polymerases move, known as their conformational dynamics, is a critical component of their relative susceptibility to drugs.”
Proteins, including polymerases, are not rigid, motionless objects. Instead, they are flexible and dynamic.Composed of amino acids, they initially fold into a steady, three‐dimensional shape known as the native conformation — their baseline structure. But as a result of various bonding and dispersing forces, the different parts of proteins can move when they come into contact with other cellular components as well as through external influences, such as changes in pH or temperature. For example, the fingers of a polymerase protein can open and close, as would the fingers of a hand.
Conformational dynamics — the ability of different parts of a protein to move — allow them to efficiently administer many essential functions with a limited number of ingredients. A better understanding of polymerase conformational dynamics is the missing link between structures and functions, including whether a protein responds to a drug and whether it could become resistant to it down the road.
Unraveling the mystery
Many structural studies have captured DNA polymerases in various distinct conformations. However, a detailed understanding of the impact of polymerase conformational dynamics on drug resistance is lacking. To solve the puzzle, the researchers carried out a series of experiments, focusing on two common polymerase conformations — an open one and a closed one — to determine how each affects drug susceptibility.
First, using cryo-EM, they conducted structural analysis to get high-resolution visualizations of the atomic structures of HSV polymerase in multiple conformations, as well as when bound to the antiviral drugs acyclovir and foscarnet. The drug-bound structures revealed how the two drugs selectively bind polymerases that more readily adopt one conformation versus another. One of the drugs, foscarnet, works by trapping the fingers of the DNA polymerase so that they are stuck in a so-called closed configuration.
Further, structural analysis paired with computational simulations suggested that several mutations that are distant from the sites of drug binding confer antiviral resistance by altering the position of the polymerase fingers responsible for closing onto the drug to halt DNA replication.
The finding was an unexpected twist. Up until now, scientists have believed that polymerases closed partially only when they attached to DNA and closed fully only when they added a DNA building block, a deoxynucleotide. It turns out, however, that HSV polymerase can fully close just by being near DNA. This makes it easier for acyclovir and foscarnet to latch on and stop the polymerase from working, thus halting viral replication.
“I’ve worked on HSV polymerase and acyclovir resistance for 45 years. Back then I thought that resistance mutations would help us understand how the polymerase recognizes features of the natural molecules that the drugs mimic,” said study co-author Donald Coen, professor of biological chemistry and molecular pharmacology at HMS. “I’m delighted that this work shows that I was wrong and finally gives us at least one clear reason why HSV polymerase is selectively inhibited by the drug.”
Authorship, funding, disclosures
Additional authors included Sundaresh Shankar, Junhua Pan, Pan Yang, Yuemin Bian, Gábor Oroszlán, Zishuo Yu, Purba Mukherjee, David J. Filman, James M. Hogle, Mrinal Shekhar.
This work was supported by the National Institutes of Health (awards R21 AI141940 and R01 AI19838), with additional funding from a Centers for Integrated Solutions in Infectious Diseases grant.
What Enables Herpes Simplex Virus To Become Impervious to Drugs?
Source: Harvard Medical School
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health and wellness
The First Suicide and Self-Harm Cross-Industry Signal Sharing Program to be Established Under the Leadership of The Mental Health Coalition
The Mental Health Coalition
NEW YORK, Sept. 12, 2024 /PRNewswire/ — The Mental Health Coalition (MHC) announced today a new program called Thrive, the first cross-industry signal sharing program designed to help stop the spread of suicide and self-harm content across different internet platforms. The goal is to increase industry collaboration, prevent online challenges from spreading virally, and help improve early detection of content that could potentially pose a safety risk.
Suicidal and self-harm content online can manifest in diverse forms, including viral challenges, text posts, visual media (images and livestreams), etc. While approaches employed by internet companies to mitigate harmful content differ, they are crucial for safeguarding user and viewer wellbeing. The expeditious identification and removal of suicide and self-harm content through Thrive will enable companies who are part of Thrive to investigate, take action and prevent similar content from being disseminated on their platforms fostering a safer online environment. While the technological infrastructure underpinning Thrive is not new (provided by Meta, it is already used by the Tech Coalition’s Lantern program), this initiative marks the first industry-wide endeavor to address suicide and self-harm content comprehensively across different platforms.
“We at MHC are excited to work with Thrive; a unique collaborative of the most influential social media platforms that have come together to address suicide and self-harm content. Meta, Snap and TikTok are some of the initial partners to join “the exchange” committing to make an even greater impact and help save lives,” said Kenneth Cole, Founder of The Mental Health Coalition.
“The integration of signal sharing, coupled with cross-industry collaboration and moderated by an independent and neutral intermediary, represents a major breakthrough in industry collaboration and public protection on the global, public health crisis of suicide and ultimately save lives,” said Dr. Dan Reidenberg, Director of Thrive.
Thrive will leverage a centralized technology platform, enabling the aggregation of information from diverse sources (platforms), where participating companies can receive alerts of content that raises concerns or contravenes their respective company policies or community standards against suicide and self-harm. Platforms are then able to independently assess whether to take action on the content. This new signal sharing program will be underpinned by a technical infrastructure provided by Meta which allows tech companies to securely share signals about content that breaks their suicide and self-harm policies. This approach addresses harmful content while respecting the autonomy of each organization’s moderation strategies, reduce the risk of contagion or content becoming viral across platforms and ensure measures exist and only share de-identified signals to protect the users privacy. There will be no personally identifiable information shared through Thrive.
“At Meta, we have strict rules against content that encourages, glorifies or shows graphic suicide or self-harm, and remove it whenever we become aware of it. Unfortunately this content isn’t limited to any one platform – especially when it comes to viral challenges – and it’s imperative that the technology industry works together to help prevent it from spreading. That’s why we’re proud to partner with the Mental Health Coalition and our peers to launch Thrive, and help keep people safe across the many apps they use.” Antigone Davis, VP of Global Safety at Meta.
“The safety and well-being of the Snapchat community is a top priority. Our dedicated teams, technologies, policies, and partnerships help keep our community safe, healthy, and informed, and our well-being features are designed to educate and empower individuals who might be struggling with their own social and emotional well-being. We are honored to be founding members of the Thrive initiative – an opportunity to continue to work industry-wide on approaches that strengthen capabilities to halt the spread of self-harm content.” Jacqueline Beauchere, Global Head of Platform Safety, Snap
“TikTok is an uplifting and entertaining part of many people’s day, and we continually invest in protecting and securing our community’s experience. By becoming a founding member of The Mental Health Coalition’s Thrive, we’re strengthening how we prevent harmful suicide and self-harm content online. Through this important collaboration and collective action, we hope to keep people safe on TikTok and beyond.” Valiant Richey, Global Head of Outreach and Partnerships, Trust and Safety, TikTok
Thrive’s Director will oversee operational aspects of the program, ensuring its effective functioning through convening, facilitating, moderating, and monitoring activities. Participating companies will assume responsibility for uploading, reviewing and taking the appropriate action on the content shared through Thrive and leveraging the platform to share insights and best practices. Dr Reidenberg will collaborate with other signal sharing exchange directors on optimal moderation strategies, lessons learned, and transparency protocols. An annual report will be issued to provide insight into the exchange’s use and impact.
Meta, Snap, and TikTok have pledged their support and participation as founding members, with other companies expected to join.
The Mental Health Coalition relies on donations. If you want to help support Thrive and the lifesaving work of the Coalition, please contact Dr Dan Reidenberg.
About The Mental Health Coalition
The Mental Health Coalition (www.thementalhealthcoalition.org), is a coalition of the Nation’s leading mental health organizations, brands, and individuals who have joined forces to end the debilitating stigma surrounding mental health and to change the way people talk about, and care for, mental illness. Our mission is to catalyze like-minded communities to work together to destigmatize mental health and empower access to vital resources and necessary support for all.
The Mental Health Coalition was formed with the understanding that the mental health crisis is fueled by a pervasive and devastating stigma, preventing millions of individuals from being able to seek the critical treatment they need. We will not relent until mental health is no longer associated with stigma, shame or judgment and all people feel empowered to openly discuss and address their individual mental health needs.
SOURCE The Mental Health Coalition
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(Family Features) Fall brings cooler days and more time indoors. This makes it easier for viruses like influenza (flu), COVID-19 and respiratory syncytial virus (RSV) to spread. These illnesses can be especially risky for pregnant people and newborns. Getting vaccinated for flu, COVID-19 and RSV during your pregnancy lets you pass protection to your baby. Your immunity helps keep them from getting very sick from one of these viruses in their first few months of life.
Virus Vaccines
Vaccines for flu and COVID-19 also protect expectant parents from serious symptoms. Pregnant people are more likely to need medical care or hospitalization for flu and COVID-19 than people their age who are not pregnant, according to the Risk Less. Do More. Public Education Campaign.
“It makes sense that people are very careful about the health choices they make during pregnancy,” said Manisha Patel, MD, MS, MBA, Chief Medical Officer of the National Center for Immunization and Respiratory Diseases. “The good news is that flu and COVID-19 vaccines are the best way to protect you and your baby against serious disease. RSV vaccines cut by more than half the risk of your baby being hospitalized for severe RSV disease, the leading cause of hospitalization for infants in the United States.”
Here are some key facts about pregnancy and vaccination:
Getting vaccinated protects you during and after pregnancy.
Common respiratory viruses can be dangerous for people who are pregnant or have recently been pregnant. This is because respiratory illnesses during pregnancy are more likely to be severe. Studies show that the flu and COVID-19 vaccines are the best protection for pregnant people. They lower the risk of serious illness, hospitalization and death. Like medications, vaccines can cause side effects, but side effects from flu and COVID-19 vaccines are almost always mild and brief. The benefits of these vaccines outweigh the risks for most people.
The Centers for Disease Control and Prevention also recommends an RSV vaccine during pregnancy. Vaccination during pregnancy cuts the risk of a newborn being hospitalized with RSV by half.
Getting vaccinated protects your unborn or nursing child.
Flu, COVID-19 and RSV viruses are dangerous for both unborn and newborn children. About 20,000 children under age 5 in the U.S. are hospitalized with flu each year. Infants under 6 months are at the highest risk of serious complications. Infants are also at higher risk for RSV. In fact, it’s the top reason babies in the U.S. are hospitalized.
When a pregnant person gets vaccinated for flu, COVID-19 or RSV, they share their immunity with their child. Recent studies also show that some breastfeeding parents maintain infection-fighting antibodies in their breastmilk after vaccination. This immunity can also help protect their baby.
Timing for vaccinations is important.
Getting vaccinated for flu, COVID-19 and RSV during pregnancy builds antibodies that can help protect the baby. Get the yearly COVID-19 and flu vaccines this fall season. For RSV, it is recommended that pregnant people get vaccinated between 32-36 weeks of pregnancy during the RSV season, which is from September-January in most parts of the United States.
If you have questions or concerns, talk to your doctor. Knowing the facts about vaccination and pregnancy can offer confidence and comfort. Visit cdc.gov/RiskLessDoMore to learn more and talk with your doctor about getting your flu, COVID-19 and RSV vaccines.
Photo courtesy of Shutterstock
SOURCE:
United States Department of Health and Human Services
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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Newswise — SAN FRANCISCO, Calif. — The American Academy of Ophthalmology is sounding the alarm on over-the-counter eye drops advertised as eye color-changing solutions. These products are not FDA approved, have not been tested for safety or efficacy, and could potentially damage the eyes.
“Consumers seeing these products on TikTok or elsewhere online need to know that they are not FDA approved,” said JoAnn A. Giaconi, MD, clinical spokesperson for the American Academy of Ophthalmology. “The ads show dramatic before-and-after shots and vague information on how the drops actually work to change eye color. But here’s the reality, there’s no evidence that they do anything at all, and no evidence that they’re safe.”
Because the products are not FDA approved, they have not undergone rigorous safety and efficacy testing, and it’s unclear if Current Good Manufacturing Practice regulations were followed during production. Unregulated manufacturing facility conditions can lead to contaminated products that can cause dangerous eye infections.
Eye Color-Changing Drops
Potential safety risks of using unregulated eye drops include:
- Inflammation
- Infection
- Light sensitivity
- Increased eye pressure or glaucoma
- Permanent vision loss
Manufacturers claim that the drops include an ingredient that adjusts natural levels of melanin in the iris, the colored part of the eye. But there is no evidence that the formula can target the iris pigment. And if the drops did destroy the pigmented cells in the iris, it could potentially harm the eye, causing light sensitivity, eye inflammation, and eventually vision loss. It’s also unclear how other parts of the eye that rely on melanin to function properly, such as the retina, would react to this ingredient.
“Social media and the internet are full of potentially dangerous eye health claims. Bottomline, the Academy advises the public to never put anything in the eye that isn’t made to go in the eye,” Dr. Giaconi said. “You’re putting yourself at risk for painful eye conditions or even blindness.”
The safest way to change eye color is with colored contact lenses, but only if the lenses are prescribed, dispensed, and fitted by a qualified eye health professional.
For more information about eye health and how to protect your eyes, visit the Academy’s EyeSmart website.
About the American Academy of Ophthalmology
The American Academy of Ophthalmology is the world’s largest association of eye physicians and surgeons. A global community of 32,000 medical doctors, we protect sight and empower lives by setting the standards for ophthalmic education and advocating for our patients and the public. We innovate to advance our profession and to ensure the delivery of the highest-quality eye care. Our EyeSmart® program provides the public with the most trusted information about eye health. For more information, visit aao.org.
Source: American Academy of Ophthalmology (AAO)
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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