Researchers at the University of Virginia (UVA) School of Medicine, and collaborators in China and Poland have developed a database, called virusMED (virus Metal binding sites, Epitopes, and Drug binding sites), as a freely available resource to help speed the development of vaccines and treatments against viral diseases. Accessed through the https://virusmed.biocloud.top portal, virusMED lays out everything known about the atomic structure and potential vulnerabilities of more than 800 virus strains from 75 different virus families, including SARS-CoV-2, influenza, Ebola, and HIV‑1.
“The battle with COVID-19 is not over yet, but we cannot wait to start preparing for the next pandemic,” said Wladek Minor, PhD, the Harrison distinguished professor of molecular physiology and biological physics at UVA. “VirusMED is a step towards an advanced information system that brings together researchers with diverse expertise to tackle complex biomedical challenges. The information contained in virusMED will help viral researchers from many disciplines, especially those working on drug design or anti-viral therapies. We provide novel structural analysis and integrate pertinent information from various resources to provide a comprehensive picture of the proteins’ most important and vulnerable regions.”
Minor and collaborators reported on the development of virusMED in IUCrJ, in a paper titled, “virusMED: an atlas of hotspots of viral proteins.” Several of the collaborators, including lead investigator, Heping Zheng, PhD, are former students and members of Minor’s lab at UVA.
Viral infections are initiated when virus surface proteins interact with receptors on the host cell, followed by invasion of the target cell through a different mechanism, the authors explained. Metal binding sites, antigen epitopes, and drug binding sites are what’s referred to as the hotspots in viral proteins that control how viruses interact with their hosts, and make good starting points for new drug and vaccine development.
Previously, that collection of knowledge about virus data had been spread across multiple resources and often “siloed” so that it was not easily accessible, Minor said. There are already many very good databases that focus on, for example, drug-gene interactions, and drug resistance, and there is some information about epitopes, small molecule binding sites, and metal binding sites of viral proteins “scattered among half a dozen other resources,” the team noted. And while there are also databases developed to focus on virulence factor-host interactions or virus-host interactions, and resources investigating intermolecular interactions for specific classes of virus, “… there is no currently available database systematically indexing the hotspots and intermolecular interaction on the structures of all viral proteins, which could provide a framework for the design of candidate drugs targeting viral infections,” the investigators pointed out.
The database aims to put the type of critical information, including extensive information on virus species and strains, hosts, viral proteins, and antibodies, as well as FDA-approved drugs, and other important scientific data, at scientists’ fingertips, in one location. “virusMED … is a rich internet application based on a database of atomic interactions around hotspots in 7,041 experimentally determined viral protein structures. [There were] 25306 hotspots from 805 virus strains from 75 virus families characterized, including influenza, HIV-1, and SARS-CoV-2 viruses … The hotspots on viral protein structures described herein are local sequence and structural features that facilitate the binding of small molecules or other macromolecules.” With virusMED, researchers can browse the information by virus or by their hotspot of interest.
Identifying and characterizing the hotspots on the viral proteins and the corresponding receptor-binding interfaces represents what they call a vital step in further research into the molecular mechanisms of viral pathogenesis, and the rational design of molecular agents for use in diagnostic and therapeutic strategies against viruses.
This new panorama of the proteins of potential threats will help scientists respond quickly and effectively against the next pathogen poised to wreak havoc on humanity, the researchers believe. Minor and his collaborators compare the resource to Google Maps, in that it organizes and annotates major points of interest on a virus that scientists can use as a roadmap in drug and vaccine development. “Just as Google Maps organizes and annotates points of interest, virusMED presents the positions of individual hotspots on each viral protein and creates an atlas upon which newly characterized functional sites can be placed as they are being discovered,” the team noted.
“One of the most promising strain-indifferent antibody therapies developed for the treatment of COVID-19 used this type of information to improve upon a unique antibody isolated from a survivor who was infected by the SARS virus back in 2003,” said David Cooper, PhD, research faculty in Minor’s lab. “People who are surprised by rapid drug and vaccine design don’t realize that researchers today are building upon decades of previous research.”
“One of the goals of my lab is to make tools that other scientists can use. We look at the forest and find ways to help others focus on the trees,” Minor added. “Resource generation is not glamorous, but the ultimate goal of science is to make life better.” And as the researchers concluded, “The virusMED portal … can serve as a window to a valuable resource for many areas of virus research and play a critical role in the rational design of new preventative and therapeutic agents targeting viral infections … The creation and publication of databases such as virusMED is only the first step in changing the way that researchers will interact with scientific information in the future.”