HIGH RESOLUTION OF HUMAN RHINOVIRUS SEROTYPE COMPLEXED W/ ANTIVIRAL COMPOUNDS

University Of Chicago, Chicago IL

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Abstract

The aim is to collect high resolution cryo data of a number of antiviral compounds complexed to different serotypes of human rhinoviruses. Background: Human rhinoviruses (HRV) account for a majority of the common colds. Although a number of crystal structures of several rhino-viral serotypes and their complexes with anti-rhinoviral compounds have elucidated many structural features important for inhibition, quantitative studies correlating the activities of these anti-virals with the crystal structures of their complexes have not been reported. One of the main reasons is the lack of availability of a large data base of well-refined crystal structures of these complexes. High sensitivity of rhinovirus crystals to radiation damage at room temperatures has resulted in incomplete data sets of limited resolution and quality. Consequently, it has not been possible to refine the structures. Moreover, it required several hundred crystals typically to collect one data set. This limited the number of complexes that could be studied. Cryo data sets from rhinovirus crystals extend to beyond 2A and show much better completeness. Besides, only one crystal is required to collect a complete data set. It is proposed to collect high resolution cryo diffraction data from several HRV serotypes complexed to different anti-viral compounds in order to correlate quantitatively the activities of these compounds with the crystal structures of their complexes. Monochromatic cryo-diffraction data sets from crystals of different HRV serotypes will be collected and processed.