Gold compounds could lead to new approaches in HIV drug development

An artist’s rendering of a gold compound interacting with a zinc protein on the cover of the scientific journal Chemical Communications by the Royal Society of Chemistry in the United Kingdom. Nicholas Farrell, Ph.D. has found that gold compounds impede a specific zinc protein’s role in HIV infectivity.

Virginia Commonwealth University researchers have discovered that gold compounds can be effective at reducing the infectivity of HIV in laboratory experiments.

The experiments have shown gold compounds may inhibit HIV by binding to an essential zinc-based protein and changing the shape of the protein, which prevents its attachment to DNA and RNA. The zinc-based proteins occur widely in nature and have roles in the progression of many diseases.

“This finding could eventually lead to HIV-fighting therapeutics and open up a new direction in the field of medicinal inorganic chemistry,” said Nicholas Farrell, Ph.D., principle investigator on the experiments and a professor in the Department of Chemistry in the College of Humanities and Sciences.

Previous studies from other researchers have shown some anti-HIV activity for gold compounds, which have a long history in medicine and also have been used to specifically to treat rheumatoid arthritis. But Farrell’s work elucidating the mechanisms of gold compound and zinc protein interactions suggests new pathways for this action. His research was funded by the National Science Foundation.

Gold fingers

Before the zinc protein was exposed to the gold compound, zinc was bound in looped, finger-like structures to sulfur and nitrogen atoms in the protein’s cysteine — an amino acid that contains sulfur. The gold compound, which also takes on the finger-like quality of zinc, binds to cysteines because it has a high affinity for sulfur. The protein then changes from a tetrahedral shape (a pyramidal form) to a linear form. As a result, the protein is no longer able to bind to DNA and RNA, which impedes viral infectivity, Farrell said.

The researchers also used the diagnostic technique of mass spectrometry to identify the exact way gold replaces zinc in the protein. Mass spectrometry identifies and quantifies a specified molecule based on the molecule’s composition. A novel use of ion mobility mass spectrometry allowed the VCU researchers to separate the possible types of protein formed after interaction with the gold compound and to examine protein structure.

Top honors

Farrell’s findings were detailed in two papers — one featured in Chemical Communications at the beginning of 2017 and one featured in Angewandte Chemie this spring. The paper published in Angewandte Chemie was named a “Hot Paper,” which means it was chosen by editors for its importance in a rapidly evolving field of high interest.

Co-investigators on the initial paper include: Sarah R. Spell, Ph.D., and Erica J. Peterson, lab manager in the VCU Department of Chemistry; John B. Mangrum, Ph.D., and Daniele Fabris, Ph.D., in the Department of Chemistry at the University at Albany; and Roger Ptak, Ph.D., senior program leader of In Vitro Antiviral Drug Development at the Southern Research Institute.

Farrell was joined on the second publication by postdoctoral fellow Zhifeng Du, Ph.D., visiting graduate student Raphael E.F. De Paiva, Ph.D., in the Department of Chemistry and Kristina Nelson, Ph.D, director of the Proteomic Mass Spectrometry Core Facility and research assistant.

VCU awarded $1.2 million grant to study transition to employment for military dependents with autism spectrum disorder

Paul H. Wehman, Ph.D.

Researchers at Virginia Commonwealth University have received a $1.2 million grant to investigate the impact of an evidence-based program that supports military dependents with autism spectrum disorder who are seeking employment after graduating high school.

The Congressionally Directed Medical Research Program grant is funding a study measuring the impact of “Project SEARCH plus ASD Supports” on employment outcomes for military dependents with autism between the ages of 18 and 22.

This is the first known intervention study that specifically targets transition aged military dependents with autism, a group frequently described as doubly disadvantaged by their disability and their family member’s service.

The principal investigator is Paul Wehman, Ph.D., a professor in the Department of Physical Medicine and Rehabilitation in the VCU School of Medicine and in the Department of Counseling and Special Education in the VCU School of Education.

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VCU researcher develops Lyme disease diagnostic and comes closer to creating a human vaccine

The Ixodes scapularis tick (deer tick) is a known Lyme disease vector.

A Virginia Commonwealth University researcher has developed a test to more effectively detect Lyme disease in humans. And after successfully developing a Lyme disease vaccine for canines last year, VCU researchers are now closing in on a human vaccine for the disease.

Next week, Richard T. Marconi, Ph.D., professor in the School of Medicine’s Department of Microbiology and Immunology, will be awarded a $510,000 one-year grant from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, to advance the development of a human Lyme disease vaccine. In addition to NIH support, this effort is supported by the Stephen & Alexandra Cohen Foundation.

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VCU lab 3-D scans mastodon fossils, helping researchers around the world study the massive Ice Age animal

Jerre Johnson, Ph.D., professor emeritus of geology at the College of William and Mary, brought a number of mastodon fossils, including this tooth, to VCU last week to be 3-D scanned.

Boxes upon boxes filled with the fossilized remains of a mastodon that died in Virginia more than 18,000 years ago are being hauled up the steps to Virginia Commonwealth University’s Virtual Curation Laboratory, where the massive Ice Age animal’s fossils — including the tip of a tusk, a very worn tooth, toe bones, a rib bone and a mandible — are slated to be 3-D scanned.

“Mastodon,” said Bernard Means, Ph.D., director of the lab, which specializes in 3-D scanning and printing of historic and archaeological objects. “It’s what’s for breakfast.”

The fossils, dating to 16,260 B.C., were excavated from a site near Yorktown between July 2015 and last November and are the most significant mastodon remains to be found east of the Blue Ridge Mountains.

The mastodon’s tooth was first discovered in 1983 by a bricklayer named Lawnell Hart, who then enlisted the help of College of William and Mary geology professor Jerre Johnson, Ph.D. Hart and Johnson visited the site again and found additional fossils, but the property owners would not grant them permission to conduct a proper excavation.

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Study co-authored by VCU undergraduate reveals new insights into the dining habits of toucans

The keel-billed toucan was one of two species of toucans that were documented by the team to prey upon eggs of ground-nesting birds in Costa Rica.

While Toucans’ diets consist primarily of fruit, new research co-authored by a Virginia Commonwealth University biology major suggests the bird species’ dining habits are actually more opportunistic than previously believed and include the eggs of ground-nesting birds.

Maria Vera, a student in the Department of Biology in the College of Humanities and Sciences, was part of a small team of undergraduate students and researchers who traveled to Costa Rica last summer for a nine-week National Science Foundation Research Experiences for Undergraduates program to conduct a nest predator study.

As part of the study, the team built artificial bird nests on the forest ground and monitored the fake nests with camera traps. The cameras picked up two species of toucan descending to the ground to consume the eggs, marking what the team believes may be the first report of the bird preying upon nests on the forest floor.

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VCU researchers receive $2.1 million grant to investigate genetic markers for schizophrenia

The National Institute of Mental Health has awarded a $2.1 million grant to Virginia Commonwealth University’s Center for Biomarker Research and Precision Medicine to study potential epigenetic causes of schizophrenia.

The purpose of the four-year grant is to study DNA methylation as it relates to the development of schizophrenia. Methylation is a process that involves small changes to DNA that can be inherited or be the result of environmental factors such as smoking, dietary habits and medical treatment.

“DNA methylation changes over time,” said principal investigator Karolina Aberg, Ph.D., associate director of the Center for Biomarker Research and Precision Medicine and assistant professor at VCU School of Pharmacy. “Age is one aspect that changes methylation patterns, but habits like what you eat and drink and how much you exercise can also have an effect.”

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Research report: The numbers behind the innovation

Research conducted at VCU's Rice Rivers Center is one example of more than $218.9 million in university research expenditures.

Research conducted at VCU’s Rice Rivers Center is one example of more than $218.9 million in university research expenditures.

The impact of Virginia Commonwealth University researchers is wide-ranging — they have patented a canine vaccine for Lyme disease, led a nationwide effort to study concussions and aided the resurgence of sturgeon in the James River.

Those are a few of the ongoing accomplishments made with $218.9 million in VCU research expenditures, according to the National Science Foundation’s Higher Education Research and Development Survey, which outlines higher education expenditures in the U.S. for fiscal year 2015.

Nationwide funding for university research has declined the past four years. Still, VCU ranked among the top 100 institutions for the highest total expenditures dedicated to research in 2015, according to the report. The university has held this distinction three times in the past 10 years. VCU also has been ranked for five consecutive years by the NSF as a top 100 research university based on federal research expenditures. Presently, VCU is ranked No. 81 in that category, with $142.4 million in federal research expenditures for fiscal year 2015.

“It’s a fitting tribute to the community of VCU scholars who continue to propel our research enterprise upward even in times of economic adversity,” said Francis Macrina, Ph.D., vice president for research and innovation at VCU.

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VCU Engineering receives funding to improve access to AIDS drugs

B. Frank Gupton, Ph.D.

B. Frank Gupton, Ph.D.

The Virginia Commonwealth University School of Engineering’s Medicines for All project has received approximately $5 million from the Bill & Melinda Gates Foundation to develop a more cost-effective way to manufacture Dolutegravir, a new HIV/AIDS therapy.

The grant is the third major investment in Medicines for All in three years from the Gates Foundation, which also funded the initiative’s work to bring down the cost of the first-line AIDS treatments nevirapine and tenofovir.

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Researcher receives $2.5M grant to assist young people with intellectual disabilities gain completive employment

Katherine Inge, Ph.D.

Katherine Inge, Ph.D.

Virginia Commonwealth University researcher has received a five-year, $2.5 million

grant to help young people with intellectual and developmental disabilities — including autism spectrum disorder — to achieve competitive employment based on the individual’s choices, interests and skills.

The research grant from the National Institute on Disability Independent Living, and Rehabilitation Research in the U.S. Department of Health and Human Services was awarded to Katherine Inge (B.S.’75/AHP; Ph.D’95/E), Ph.D., director of the Rehabilitation Research and Training Center on Employment of People with Physical Disabilities in the VCU School of Education.

Rice Rivers researchers locate two juvenile Atlantic sturgeon

Matthew Balazik, Ph.D., holds a juvenile Atlantic sturgeon.  Photos by Ron Lopez.

Matthew Balazik, Ph.D., holds a juvenile Atlantic sturgeon.
Photos by Ron Lopez.

When Matthew Balazik (B.S.’05/H&S; M.S.’08/H&S; Ph.D.’12/LS), Ph.D., told colleagues he planned to sample fish from the James River right before an important presentation at the Rice Rivers Center, they pressed him to be back on time.

Cutting his trip short, he set his nets to find fish closer to the center. There, Balazik found something he has spent the last decade searching for: a juvenile Atlantic sturgeon.

“I was pulling the net over the side of the boat. I went down to grab it, thinking it was a blue catfish,” he said.  “Once I saw what it was I just stood there and stared at it for probably 10 seconds.”

In a case of lightning striking twice, the next day Balazik found a second juvenile Atlantic sturgeon. These are the first juvenile of that species found in the James in more than a decade. The discovery lends hope to Rice Rivers researchers studying this endangered species with support from the National Oceanic and Atmospheric Administration and the Virginia Department of Game and Inland Fisheries.

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