Our current and future studies will be directed in 3 areas related to viral envelope proteins: (i) dynamics; (ii) antivirals; (iii) airborne pathogen detection.

With respect dynamics, we will continue to characterize transient states of viral envelope proteins, which we believe play critical roles in function and antiviral development. Recently, we have determined the x-ray structure of a drug-like molecule bound to an interior (non-solvent exposed or “cryptic” site) of hemagglutinin (unpublished data). Binding of this molecule requires large scale dynamic motions of the protein backbone, which have never before been observed and may be critical to hemagglutinin function. Moreover, we suggest that cryptic sites exist in many proteins and that the consideration of protein dynamics is critically important for rational drug design.

With respect to antivirals, we have characterized numerous inhibitors of viral entry by NMR, as discussed above, and we will continue to collaborate with medicinal chemists­ and virologists in academia (at UIC and elsewhere) and in industry (Microbiotix, Inc. and Chicago Biosolutions, Inc.) to optimize these compounds with the goal of in vivo efficacy. To date, the antiviral treatments against influenza are limited and thus it will be critically important to develop novel antivirals in the future, particularly with potential epidemics arising from avian strians (“bird flu”) that exhibit >50% mortality in humans. Notably our NMR-based approach to identify and guide chemical optimization is unique and presents the potential for rapid interations of chemical optimization.

Finally, with respect to airborne pathogen detection, we are currently collaborating with Igor Paprotny (UIC) to develop a device for real-time detection of airborne viral pathogens, with my laboratory working on the biochemistry of detection by protein or nucleic acid based techniques to detect viral envelope proteins and Dr. Paprotny’s laboratory working on the collection and manipulation using microfluidics. Our initial focus is on SARS-CoV-2, the causitive agent of COVID-19, which we feel will be present for the forseeable future due to the limitations of vaccines (distribution, compliance, duration, and mutant resistance). Notably, our laboratory has recently shown the ability to distinguish wild-type from mutant strains (e.g. the UK or Indian variants) and this aspect is now being incorporated into our device. Importantly, the device can be quickly adapted for the detection of other airborne pathogens (e.g. avian influenza, other CoV, or viruses infecting livestock). In summary, we feel that our expertise in viral envelope proteins, as well as our expertise in multisdisciplinary approaches, will greatly benefit these and future research efforts.

Peer Reviewed Published Articles (109 total, 4338 citations, h-index=40)