Breaking News
March 19, 2019 - Use of synthetic psychedelic linked to improvements in depression and anxiety
March 19, 2019 - Knee Pain Not Tied to Activity Levels in Knee Osteoarthritis
March 19, 2019 - Study shows benefits of delayed cord clamping in healthy babies
March 19, 2019 - A cell’s “self-destruct” function could yield new therapies
March 19, 2019 - Latest advances and perspectives of all AI types used in pharmaceutical R&D
March 19, 2019 - Prophylactic cranial irradiation used as standard approach for patients with NSCLC
March 19, 2019 - Sugar-sweetened beverages may be linked with increased risk of cardiovascular mortality
March 19, 2019 - AHA News: Black Woman in Their 50s Face Especially High Stroke Risk
March 19, 2019 - Secrets of early life revealed from less than half a teaspoon of blood
March 19, 2019 - Immune cells engineered to tattle on suspicious cells in the body
March 19, 2019 - Heart attack patients who are taken to heart care centres directly survive longer
March 19, 2019 - IVF babies have increased in birthweight over the past 25 years, study reveals
March 19, 2019 - Study highlights the need for psychiatric care to be integrated into cancer treatment
March 19, 2019 - Testosterone treatment lowers recurrence rates in low-risk prostate cancer patients
March 19, 2019 - Caterpillars could hold the secret to new treatment for Osteoarthritis
March 19, 2019 - Parkinson’s treatment delivers a power-up to brain cell ‘batteries’
March 19, 2019 - Stanford launches new Institute for Human-Centered Artificial Intelligence
March 19, 2019 - Wireless earphones may cause cancer
March 18, 2019 - ACC/AHA guideline for prevention of cardiovascular disease released
March 18, 2019 - UTA nursing professor receives $6.575 million to attack musculoskeletal diseases
March 18, 2019 - Gene medication shows promise to treat spinal cord injuries
March 18, 2019 - First Human Study of “Robotic” RaniPill™ Capsule to Replace Injections Announced by Rani Therapeutics
March 18, 2019 - Food Allergy Testing: MedlinePlus Lab Test Information
March 18, 2019 - Altered brain activity patterns of Parkinson’s captured in mice
March 18, 2019 - Apple Heart Study demonstrates ability of wearable technology to detect atrial fibrillation | News Center
March 18, 2019 - Cardiovascular benefits of diabetes drug extend across a wide spectrum of patients, shows study
March 18, 2019 - Novel cardiac pump shows superior outcomes in patients with advanced heart failure
March 18, 2019 - U.S. FDA Grants Priority Review for Fedratinib New Drug Application in Myelofibrosis
March 18, 2019 - Living like a caveman won’t make you thin—but it might make you healthy
March 18, 2019 - Modified immune cells issue alert when detecting cancer in mice | News Center
March 18, 2019 - Dementia caregivers design robots for alleviating stress and increasing joyful moments
March 18, 2019 - VR technology could help improve balance in humans
March 18, 2019 - Study demonstrates effective way to slow progression of cerebrovascular disease in older adults
March 18, 2019 - Premature babies also have protective anti-viral antibodies
March 18, 2019 - Painkillers taken by pregnant mothers unlikely to cause asthma in the child
March 18, 2019 - Fibromyalgia can be reliably detected in blood samples
March 18, 2019 - Marijuana use has dropped among most teens after legalization
March 18, 2019 - Legacy Pharmaceutical Packaging, LLC Issues Voluntary Nationwide Recall of Losartan Potassium Tablets, USP, 25mg, 50mg, And 100mg Due to The Detection of Trace Amounts Of N-Nitroso N-Methyl 4-Amino Butyric Acid (NMBA) Impurity Found in The Active Pharmaceutical Ingredient (API)
March 18, 2019 - Researchers identify early home and family factors that contribute to obesity
March 18, 2019 - Fate and festivity: Match Day 2019
March 18, 2019 - Study finds TAVR to be as good as open-heart surgery for patients at low surgical risk
March 18, 2019 - EU-funded project is developing new tools for diagnosing cancer
March 18, 2019 - Gluten, lactose, food dyes in pills could be causing side effects finds study
March 18, 2019 - Taking painkillers during pregnancy is not responsible for asthma risk in children, study shows
March 18, 2019 - Prediagnosis Psychiatric Care Linked to Worse Cancer Mortality
March 18, 2019 - Paris hospital halts stool study after donor deluge
March 18, 2019 - Partial oral antibiotic therapy shows efficacy and safety in patients with infectious endocarditis
March 18, 2019 - Olympus improves access to science education through BioBus collaboration
March 18, 2019 - Depression screening does not improve quality of life in heart attack patients
March 18, 2019 - Echocardiography may aid in patient selection for TMVR
March 18, 2019 - Are ‘Inactive’ Ingredients in Your Drugs Really So Harmless?
March 18, 2019 - Wearable technology can safely identify atrial fibrillation
March 18, 2019 - Scientists tackle rare retinal disease in unique research project
March 18, 2019 - Death By A Thousand Clicks
March 18, 2019 - Absorbable, antibiotic-eluting envelope can reduce rate of cardiac device infections
March 18, 2019 - Hormonal treatment associated with depression in men with prostate cancer
March 18, 2019 - Porvair Sciences launches reinforced 96-well deep round microplate
March 18, 2019 - Simplified catheter ablation could slash waiting lists for atrial fibrillation patients
March 18, 2019 - BFR therapy as part of rehabilitation following ACL surgery may slow bone loss
March 18, 2019 - A human model to test implants for cataract surgery
March 18, 2019 - New risk adjustment model could reduce financial penalty for safety net hospitals
March 18, 2019 - NHS cancer patients’ wait to start treatment worrying
March 18, 2019 - Inventiva Announces Results from Phase IIb Clinical Trial with Lanifibranor in Systemic Sclerosis
March 18, 2019 - Cologuard
March 18, 2019 - Researchers find evidence of prenatal environment tuning genomic imprinting
March 18, 2019 - Dolomite Bio launches novel Nadia product family for single-cell research
March 18, 2019 - Intellipharmaceutics Announces Resubmission of New Drug Application to the U.S. FDA for its Oxycodone ER
March 18, 2019 - Excessive gestational weight gain tied to maternal morbidity
March 18, 2019 - RCEM issues position statement on metrics to supplement four-hour standard target
March 17, 2019 - Noncontrast Brain MRI Effective for Monitoring Multiple Sclerosis
March 17, 2019 - Brain region plays key role in regulation of parenting behavior, study finds
March 17, 2019 - Natural speed limit on DNA replication sets pace for life’s first steps
March 17, 2019 - New research reveals overlooked impact of herbicide glyphosate on the environment
March 17, 2019 - Molecular patterns could help predict relapse risk in breast cancer patients
March 17, 2019 - Study confirms sensitivity of microbiological cultures for detecting cholera
March 17, 2019 - Scientists Spot Clues to Predicting Breast Cancer’s Return
March 17, 2019 - Scientists identify gene that keeps PTSD-like behavior at bay in female mice
March 17, 2019 - New method would allow doctors to detect earliest stages of cancers in the lymph nodes
March 17, 2019 - Cholesterol protein discovery raises hope for smarter drugs
March 17, 2019 - New insect medium delivers high viable cell density growth and protein yield
Molecular virologist uses basic science to fight influenza

Molecular virologist uses basic science to fight influenza

image_pdfDownload PDFimage_print

Molecular virologist Chad Petit, Ph.D., uses basic science to fight influenza — through experiments at the atomic level.

This includes a deadly poultry influenza virus in China called the H7N9 avian flu virus. Since 2013, H7N9 has infected 1,625 people, killing 623. While not highly contagious for humans, just three mutations could change that, turning H7N9 into the feared Disease X, the term health experts use for the next unknown cause of a worldwide epidemic.

In research to improve influenza therapies against H7N9 and other influenza strains, Petit and his University of Alabama at Birmingham colleagues have detailed the binding site and mechanism of inhibition for two small-molecule experimental inhibitors of influenza viruses. Their report is published in the Journal of Biochemistry,

The two experimental inhibitors studied by Petit, a UAB assistant professor of biochemistry and molecular genetics, are small molecules whose precise mechanism of action was unknown. The inhibitors target the function of a key influenza protein called NS1, which has multiple roles to block the body’s immune response during influenza infection. Thus, NS1 is essential to the survival and adaptability of the influenza virus.

Petit and colleagues used nuclear magnetic resonance, or NMR, spectroscopy to probe interactions of the inhibitors with NS1. They first showed that the inhibitors — called A9 and A22 — interacted with just one of the two independently folded domains of NS1, the NS1 effector domain.

The researchers noted that the structures of both small-molecule inhibitors were very similar to a fragment of a host protein called CPSF30 that the NS1 effector domain binds in order to short-circuit the body’s immune response. Therefore, the researchers hypothesized that A9 and A22 block influenza viral replication and block NS1 function by interfering with the interaction between the NS1 effector domain and CPSF30.

NMR data revealed the particular amino acids of the NS1 effector domain that are involved in inhibitor binding. The researchers — using two significantly different NS1 proteins from distinct influenza strains, including the H7N9 strain — showed that similar sequences of amino acids in the two NS1 proteins were involved in inhibitor binding.

The 1918 “Spanish” flu NS1 protein

Besides the Chinese H7N9 NS1, the other NS1 protein tested was the NS1 effector domain from the 1918 “Spanish” flu, which infected one-third of the world’s population a century ago and killed 50 million to 100 million people.

The UAB researchers then used X-ray crystallography, led by UAB Microbiology assistant professor Todd Green, Ph.D., to determine the three-dimensional structure of the NS1 effector domain from the 1918 “Spanish” flu. This allowed them to map the A9/A22-binding site onto that structure, which confirmed their hypothesis — A9 and A22 interact with the NS1 effector domain hydrophobic pocket that is known to bind the host protein CPSF30.

The crystallography data also showed that the NS1 effector domain is able to dimerize, using an interface different from two other known dimers of the NS1 effector domain. Biological significance of this new dimer form is unknown.

“Altogether, our findings provide strong evidence for the mechanism of action of two anti-influenza compounds that target NS1, and the findings contribute significant structural insights into NS1 that we hope will promote and inform the development and optimization of influenza therapies based on A9 and A22,” Petit said.

The need for novel antiviral compounds is great. Each year, influenza strains kill 250,000 to 500,000 people worldwide, and the virus is noted for quick changes to produce pandemic strains that few people have immunity against. Viral resistance has limited the effectiveness of several earlier antiviral compounds that were developed to treat influenza.

Source:

https://www.uab.edu/news/research/item/9911-molecular-virologists-fight-influenza-at-the-molecular-level

Tagged with:

About author

Related Articles