We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
PURITAN MEDICAL

Download Mobile App




High-Resolution Cryo-EM Images Increase Understanding of Anti-Ebola Drug

By LabMedica International staff writers
Posted on 18 Aug 2016
Print article
Image: A molecular model showing the experimental antibody drug ZMapp binding to the Ebola virus, here targeting the virus\'s GP protein (Photo courtesy of Dr. Andrew Ward and Dr. Jesper Pallesen, Scripps Research Institute).
Image: A molecular model showing the experimental antibody drug ZMapp binding to the Ebola virus, here targeting the virus\'s GP protein (Photo courtesy of Dr. Andrew Ward and Dr. Jesper Pallesen, Scripps Research Institute).
High-resolution cryo-electron microscopy images have revealed more precise information as to how the experimental drug ZMapp binds to the Ebola virus and provide insights into how the drug prevents growth of the pathogen.

ZMapp, which was developed by Mapp Biopharmaceutical (San Diego, CA, USA), is composed of three monoclonal antibodies (mAbs) that have been chimerized by genetic engineering. The components are chimeric monoclonal antibody c13C6 from a previously existing antibody cocktail called MB-003 and two chimeric mAbs from a different antibody cocktail called ZMab, c2G4 and c4G7.

Investigators at The Scripps Research Institute (La Jolla, CA, USA) used high-resolution cryo-electron microscopy (cryo-EM) techniques to study the interaction between ZMapp and two Ebola glycoproteins. The more abundant glycoprotein was the secreted dimeric glycoprotein (sGP). Despite the abundance of sGP during infection, little was known regarding its structure or functional role. A minor product, resulting from transcriptional editing, was the transmembrane-anchored, trimeric viral surface glycoprotein (GP). GP mediated attachment to and entry into host cells, and was the intended target of antibody therapeutics. Because large portions of sequence were shared between GP and sGP, it had been hypothesized that sGP may potentially subvert the immune response or may contribute to pathogenicity.

Researchers have historically relied on NMR and X-ray diffraction techniques to determine the structures of molecular complexes and proteins that play a role in the causes of various disease states. Structural information about a variety of medically important proteins and drugs has been obtained by these methods. Cryo-EM is a complementary analytical technique that provides near-atomic resolution without requirements for crystallization or limits on molecular size and complexity imposed by the other techniques. Cryo-EM allows the observation of specimens that have not been stained or fixed in any way, showing them in their native environment while integrating multiple images to form a three-dimensional model of the sample.

In the August 8, 2016, online edition of the journal Nature Microbiology, the investigators presented the cryo-electron microscopy structures of GP and sGP in complex with GP-specific and GP/sGP cross-reactive antibodies undergoing human clinical trials. The structure of the sGP dimer in complex with both an sGP-specific antibody and a GP/sGP cross-reactive antibody, permitted the investigators to unambiguously assign the oligomeric arrangement of sGP and compare its structure and epitope presentation to those of GP.

"This sGP protein is tremendously important," said Dr. Erica Ollmann Saphire, a professor at the Scripps Research Institute. "This is the roadmap we need to target the right molecules in infection. Eighty to 90% of what Ebola virus makes in infection is this shed molecule. It is like a smoke screen, and we need to know where it is similar to our target GP and where it is different."

Related Links:
Mapp Biopharmaceutical
The Scripps Research Institute
Platinum Member
COVID-19 Rapid Test
OSOM COVID-19 Antigen Rapid Test
One Step HbA1c Measuring System
GREENCARE A1c
Anti-Cyclic Citrullinated Peptide Test
GPP-100 Anti-CCP Kit
New
Gold Member
Fully Automated Cell Density/Viability Analyzer
BioProfile FAST CDV

Print article

Channels

Clinical Chemistry

view channel
Image: Reaching speeds up to 6,000 RPM, this centrifuge forms the basis for a new type of inexpensive, POC biomedical test (Photo courtesy of Duke University)

POC Biomedical Test Spins Water Droplet Using Sound Waves for Cancer Detection

Exosomes, tiny cellular bioparticles carrying a specific set of proteins, lipids, and genetic materials, play a crucial role in cell communication and hold promise for non-invasive diagnostics.... Read more

Molecular Diagnostics

view channel
Image: MOF materials efficiently enrich cfDNA and cfRNA in blood through simple operational process (Photo courtesy of Science China Press)

Blood Circulating Nucleic Acid Enrichment Technique Enables Non-Invasive Liver Cancer Diagnosis

The ability to diagnose diseases early can significantly enhance the effectiveness of clinical treatments and improve survival rates. One promising approach for non-invasive early diagnosis is the use... Read more

Hematology

view channel
Image: The low-cost portable device rapidly identifies chemotherapy patients at risk of sepsis (Photo courtesy of 52North Health)

POC Finger-Prick Blood Test Determines Risk of Neutropenic Sepsis in Patients Undergoing Chemotherapy

Neutropenia, a decrease in neutrophils (a type of white blood cell crucial for fighting infections), is a frequent side effect of certain cancer treatments. This condition elevates the risk of infections,... Read more

Pathology

view channel
Image: The OvaCis Rapid Test discriminates benign from malignant epithelial ovarian cysts (Photo courtesy of INEX)

Intra-Operative POC Device Distinguishes Between Benign and Malignant Ovarian Cysts within 15 Minutes

Ovarian cysts represent a significant health issue for women globally, with up to 10% experiencing this condition at some point in their lives. These cysts form when fluid collects within a thin membrane... Read more
Copyright © 2000-2024 Globetech Media. All rights reserved.