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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(Family Features) As people prepare to gather with family and friends this holiday season, it’s important to think about health and safety.
“With the holidays just around the corner, now is the perfect time to think about how you can help protect yourself from serious illness from flu, COVID-19 and RSV – and support your loved ones in doing the same,” said Dr. Rachel Levine, assistant secretary for health at the U.S. Department of Health and Human Services (HHS). “Vaccination is an important step in having a happy and healthy celebration.”
While preparing for holiday festivities, keep these recommendations in mind to help protect yourself from severe flu, COVID-19 and RSV.
Flu: Flu season usually peaks during the winter months, so now is a great time to get the 2024-25 flu vaccine. It’s recommended for people 6 months and older to lower their risk of infection or serious illness from the flu. In fact, people who skipped their flu shot last year were twice as likely to need medical help for the flu. The best time to get vaccinated is at least a couple of weeks before a holiday gathering. But getting vaccinated later in the season can still help. Encourage your family and friends to get the flu vaccine, too. Together you can create safer holiday celebrations.
COVID-19: Getting vaccinated against COVID-19 is also important for everyone ages 6 months and older. The updated COVID-19 vaccines offer the best protection against serious illness from the virus, especially for those at higher risk. This includes people with certain health conditions or older adults, which may include parents, grandparents and great aunts or uncles. By getting vaccinated, people of all ages can lower their risk of getting severely sick. In fact, young adults are at higher risk of developing Long COVID than older adults. However, staying up to date on your COVID-19 vaccines lowers your risk of Long COVID, too.
RSV: RSV can be especially risky for older adults and babies. That’s why everyone 75 and older, people 60-74 with certain health conditions or who live in a nursing home and pregnant people should get the RSV vaccine. Pregnant people should get the RSV vaccine at 32-36 weeks of pregnancy to help protect their newborns from severe RSV during their first six months of life.
As you prepare for the holidays, remember that prevention is the best way to keep from getting seriously sick from flu, COVID-19 and RSV. By getting vaccinated now, you can enjoy the holiday season with greater confidence and less risk of missing time together. Being vaccinated helps keep your symptoms milder if you get infected after vaccination so you can do the things you want to do with less risk of spreading infection.
Talk with your doctor about which vaccines are right for you as well as for any loved ones you help care for. Visit cdc.gov/RiskLessDoMore for more information on vaccines, or visit vaccines.gov to get started.
The Effects of Flu, COVID-19 and RSV on Different Populations
People who are Black, Hispanic or who live in rural areas may be at higher risk of severe illness from flu, COVID-19 and RSV than others. Getting vaccinated is the best protection from getting seriously sick from these viruses. According to the Centers for Disease Control and Prevention (CDC):
- Last flu season, Black adults were more than twice as likely as white adults to be hospitalized for flu.
- Last flu season, Hispanic adults were more likely than white adults to be hospitalized for flu.
- One in 3 adults living in rural areas have never been vaccinated against COVID-19. For people living in rural areas, health services may be far away. That can mean it takes some planning to get vaccinated. But being far from medical care also means it’s even more important to lower your risk of serious illness by getting vaccinated.
Photos 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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Tome medidas para limitar el riesgo de enfermedad cardiovascular
(Family Features) En la última década se ha producido un aumento de factores de riesgo cardiovascular, como la hipertensión arterial no controlada, la diabetes y la obesidad, cada uno de los cuales aumenta el riesgo de desarrollar enfermedades cardíacas y accidentes cerebrovasculares. Estas tendencias están llevando a los investigadores a concluir que la prevalencia de las enfermedades cardiovasculares (ECV) seguirá aumentando.
Más del 60 % de los adultos estadounidenses tendrán algún tipo de ECV para 2050, según las proyecciones previstas de la American Heart Association, que celebra 100 años de servicio salvando vidas como la principal organización mundial sin fines de lucro dedicada a la salud del corazón y el cerebro de todos. Además, se espera que los costos totales relacionados con las ECV casi se tripliquen en ese período hasta alcanzar más de 1.8 trillones de dólares.
El aumento será impulsado por una población más anciana y diversa, pero estos factores de riesgo están aumentando incluso entre niños y adultos.
“Reconocemos que el panorama de la salud cardiovascular cambiará en las próximas tres décadas debido al tsunami que se avecina de aumentos en los costos de la atención médica, una población de mayor edad que vive más tiempo y un número cada vez mayor de personas de poblaciones de pocos recursos”, dijo la voluntaria de la American Heart Association, Karen E. Joynt Maddox, M.D., M.P.H., FAHA. “Aun así, estas siguen siendo las principales causas de muerte y discapacidad en Estados Unidos”.
Si bien se necesitan cambios sistemáticos continuos en la ciencia, las políticas y la atención de salud, la mayoría de las ECV se pueden prevenir a nivel individual. Usted puede ayudar a cambiar el rumbo de las terribles perspectivas de la ECV y, al mismo tiempo, mejorar su propia salud siguiendo y alentando a otros a seguir los “Life’s Essential 8” de la American Heart Association.
Coma mejor. Intente seguir un patrón de alimentación saludable en general que incluya alimentos integrales, frutas y verduras, proteínas magras, frutos secos, semillas y cocinar con aceite de oliva y de canola.
Manténgase activo. Los adultos deben realizar 2 horas y media de actividad física moderada o 75 minutos de actividad física vigorosa por semana. Los niños deben tener 60 minutos cada día, incluidos juegos y actividades estructuradas.
Deje el tabaco. El uso de productos que suministran nicotina por inhalación, que incluyen cigarrillos tradicionales, cigarrillos electrónicos y vaporizadores, es la principal causa de muerte evitable en los EE. UU.
Duerma bien. La mayoría de los adultos necesitan dormir entre 7 y 9 horas cada noche. Los niños de 5 años o menos necesitan entre 10 y 16 horas, incluidas las siestas; de 9 y 12 horas, en niños de 6 y 12 años, y entre 8 y 10 horas, entre los 13 y 18 años.
Controle el peso. Lograr y mantener un peso saludable tiene muchos beneficios. El índice de masa corporal es un indicador útil. El IMC óptimo es menor de 25, pero menor de 18.5 se considera bajo peso. Puede calcularlo en línea o consultar a un profesional de la salud.
Controle el colesterol. Los niveles altos de colesterol no HDL, o “malo”, pueden provocar enfermedades cardíacas. Su profesional de atención médica puede considerar el colesterol no HDL como el número preferido para monitorear, en lugar del colesterol total, porque se puede medir sin ayuno previo y se calcula de manera confiable entre todas las personas.
Controle el nivel de azúcar en sangre. La mayor parte de los alimentos que consume se convierten en glucosa (o azúcar en sangre) que su cuerpo utiliza como energía. Con el tiempo, los niveles altos de azúcar en sangre pueden dañar el corazón, los riñones, los ojos y los nervios.
Controle la presión arterial. Mantener su presión arterial dentro de rangos aceptables puede ayudarle a mantenerse saludable por más tiempo. Los niveles inferiores a 120/80 mmHg son óptimos. La presión arterial alta se define como una presión sistólica de 130 a 139 mm Hg (el número superior en una lectura) o una presión diastólica de 80 a 89 mm Hg (el número inferior).
Encuentre más formas de cuidar su salud en el nuevo año y más allá en heart.org.
Foto cortesía de Shutterstock
SOURCE:
American Heart Association
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Lifestyle
Why winter makes you more vulnerable to colds – a public health nurse explains the science behind the season
Libby Richards, Purdue University
You’ve probably heard “Don’t go outside in the winter with your hair wet or without a coat; you’ll catch a cold.”
That’s not exactly true. As with many things, the reality is more complicated. Here’s the distinction: Being cold isn’t why you get a cold. But it is true that cold weather makes it easier to catch respiratory viruses such as the cold and flu.
Research also shows that lower temperatures are associated with higher COVID-19 rates.
As a professor of nursing with a background in public health, I’m often asked about infectious disease spread, including the relationship between cold and catching a cold. So here’s a look at what actually happens.
Many viruses, including rhinovirus – the usual culprit for the common cold – influenza, and SARS-CoV-2, the virus that causes COVID-19, remain infectious longer and replicate faster in colder temperatures and at lower humidity levels. This, coupled with the fact that people spend more time indoors and in close contact with others during cold weather, are common reasons that germs are more likely to spread.
The flu and respiratory syncytial virus, or RSV, tend to have a defined fall and winter seasonality. However, because of the emergence of new COVID-19 variants and immunity from previous infections and vaccinations decreasing over time, COVID-19 is not the typical cold-weather respiratory virus. As a case in point, COVID-19 infection rates have surged every summer since 2020.
Virus transmission is easier when it’s cold
More specifically, cold weather can change the outer membrane of the influenza virus, making it more solid and rubbery. Scientists believe that the rubbery coating makes person-to-person transmission of the virus easier.
It’s not just cold winter air that causes a problem. Air that is dry in addition to cold has been linked to flu outbreaks. That’s because dry winter air further helps the influenza virus to remain infectious longer. Dry air, which is common in the winter, causes the water found in respiratory droplets to evaporate more quickly. This results in smaller particles, which are capable of lasting longer and traveling farther after you cough or sneeze.
How your immune system responds during cold weather also matters a great deal. Inhaling cold air may adversely affect the immune response in your respiratory tract, which makes it easier for viruses to take hold. That’s why wearing a scarf over your nose and mouth may help prevent a cold because it warms the air that you inhale. https://www.youtube.com/embed/7JQ78oLFV9A?wmode=transparent&start=0 Cold weather can affect nasal immunity.
Also, most people get less sunlight in the winter. That is a problem because the sun is a major source of vitamin D, which is essential for immune system health. Physical activity, another factor, also tends to drop during the winter. People are three times more likely to delay exercise in snowy or icy conditions.
Instead, people spend more time indoors. That usually means more close contact with others, which leads to disease spread. Respiratory viruses generally spread within a 6-foot radius of an infected person.
In addition, cold temperatures and low humidity dry out your eyes and the mucous membranes in your nose and throat. Because viruses that cause colds, flu and COVID-19 are typically inhaled, the virus can attach more easily to these impaired, dried-out passages.
What you can do
The bottom line is that being wet and cold doesn’t make you sick. That being said, there are strategies to help prevent illness all year long:
- Avoid touching your face, something people do between nine and 23 times an hour.
- Stay hydrated. Eight glasses a day of water is a good goal, but that could be more or less depending on lifestyle and the size of the person.
- Eat a well-balanced diet. Dark green, leafy vegetables are rich in immune system-supporting vitamins, while eggs, fortified milk, salmon and tuna have vitamin D.
- Stay physically active, even during the winter.
- Get adequate sleep.
- Clean hard, high-touch surfaces in your home often.
- If your nose or throat gets dry in the winter, consider using a humidifier.
- Get your annual flu and COVID-19 vaccine.
Following these tips can ensure you have a healthy winter season.
This is an updated version of an article originally published on Dec. 15, 2020.
Libby Richards, Professor of Nursing, Purdue University
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.
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