An international research team has manufactured a new protein that can combat deadly flu epidemics.

The paper, featured on the cover of the current issue of Nature Biotechnology, demonstrates ways to use manufactured genes as antivirals, which disable key functions of the flu virus, said Tim Whitehead, assistant professor of chemical engineering and materials science at Michigan State University.

“Our most potent design has proven effective on the vulnerable sites on many pandemic influenza viruses, including several H1N1 (Spanish flu, Swine flu) and H5N1 (Avian flu) subtypes,” said Whitehead, the paper’s co-lead author. “These new therapeutics are urgently needed, so we were especially pleased to see that it neutralizes H1N1 viruses with potency.”

From its earlier research, the team used computer-aided design to engineer proteins that targeted vulnerable sites on the highly adaptable virus. From there, researchers optimized their designer proteins by comprehensively mapping the mutations that gave the proteins a strong advantage when attacking the viruses’ targeted areas.

The team improved its proteins through a process called “DNA deep sequencing.” This allowed Whitehead and his colleagues to simultaneously sequence millions of variants of their manufactured proteins, identify and keep the beneficial mutations and optimize the proteins’ performance.

“By taking only the best mutations, we can reprogram our proteins to burrow into viruses at key locations and render them harmless,” he said. “Our work demonstrates a new approach to construct therapeutic proteins, which we hope will spur development of new protein drugs by the biopharmaceutical industry.”

This research also laid the groundwork for future treatments of all flu viruses as well as other diseases such as smallpox, Whitehead added.

Whitehead’s co-authors included researchers from the University of Washington, the Scripps Research Institute (La Jolla, Calif.), Naval Health Research Center (San Diego) and the Weizmann Institute of Science (Rehovot, Israel).

written by Journal of Antivirals and Antiretrovirals

Pharmacists and other drugstore staff already conduct tests for high-blood pressure, cholesterol levels and diabetes at in-store clinics.

Now, in a pilot program with federal health officials announced Tuesday, Walgreen Co. and other pharmacies will examine whether they can become a go-to stop for those seeking HIV testing.

So far, seven stores — including three operated by Walgreen in Chicago, Washington D.C. and Lithonia, Ga. — are offering the HIV tests for free. Spotting a patient early on with HIV decreases the likelihood the disease will be transmitted to other people and helps get an infected individual on drug treatment and therapy earlier.

By the end of the summer, the Centers for Disease Control and Prevention plans to add 17 more pharmacies to the pilot program, dividing the participating drug stores equally between urban and rural locations.

The CDC estimates 1.1 million people in the U.S. live with HIV, but nearly one in five of those infected is unaware of their condition. Health officials six years ago recommended that all adolescents and adults between the ages of 13 to 64 get tested at least once for HIV.

Testing numbers have risen in recent years. About 45% of Americans aged 18 to 64 in 2009 had reported getting tested for HIV at some point in their lives, according to CDC research, up from the 40% observed in 2006.

The two-year pilot is a test run for how drug stores and community pharmacies across the country could one day offer HIV testing. CDC officials will study the amount of time, resources and cost required.

“We want to get a sense of how cumbersome this process would be and the approximate cost of the service for the pharmacies,” Kevin Fenton, a CDC director for the center focusing on HIV/AIDS, tells the Health Blog.

The findings will help health officials establish a model that other pharmacies could follow, says Paul Weidle, the CDC epidemiologist in charge of the project.

Free HIV tests are widely available at local health departments and community organizations. Most people get tested at their doctor’s office as part of routine health screens, paying a nominal fee for the test or the visit. Test samples are collected by oral swab or from a blood sample taken by a finger prick device.

Pharmacists or nurse practitioners at the pilot clinics use an oral swab of the gums or inside the cheek. The FDA-approved HIV tests produce results within 20 minutes. If the test comes out as a preliminary positive, the patient will be referred to a local health-care provider for confirmation and care.

The tests are conducted in private rooms. “This is a non-descript type of place. Nobody really knows what you’re in there for,” said Mike Ellis, Walgreen’s vice president of specialty and infusion.

Walgreen has also trained its pharmacists in recent years to take tests for blood pressure, cholesterol and diabetes. The pharmacists who can provide counseling about HIV treatments or conduct a test receive about 25 hours of training every year, said Glen Pietrandoni, senior manager of HIV/AIDS and Hepatitis at Walgreen.

written by Journal of Antivirals and Antiretrovirals

Computational methods for accurately calculating the binding affinity of a ligand for a protein play a pivotal role in rational drug design. We herein present a theoretical study of the binding of five different ligands to one of the proteins responsible of the human immunodeficiency virus type 1 (HIV-1) cycle replication; the HIV-1 reverse transcriptase (RT). Two types of approaches are used based on molecular dynamics (MD) simulations within hybrid QM/MM potentials: the alchemical free energy perturbation method, FEP, and the pathway method, in which the ligand is physically pulled away from the binding site, thus rendering a potential of mean force (PMF) for the binding process. Our comparative analysis stresses their advantages and disadvantages and, although the results are not in quantitative agreement, both methods are capable to distinguish the most and the less potent inhibitors, according to experimental IC50 values measured in vitro. The methods can then be used to select the proper scaffold to design new drugs. A deeper analysis of these inhibitors through molecular electrostatic potential (MEP) and calculation of the binding contribution of the individual residues shows that, in a rational design, apart from the strong interactions established with the two magnesium cations present in the RNase H site, it is important to take into account interactions with His539 and with those residues that are anchoring the metals; Asp443, Glu478, Asp498 and Asp549. The MEPs of the active site of the protein and the different ligands show a better complementarity in those inhibitors that present higher binding energies, but there are still possibilities of improving the favourable interactions and decrease those that are repulsive in order to design compounds with higher inhibitory activity.

written by Journal of Antivirals and Antiretrovirals