Abstract
The objective of this project is to elucidate the exact molecular MOA of small-molecule polymerase inhibitors of RSV and hMPV. This research will significantly increase the field's understanding of how these small-molecule replication inhibitors work and ultimately contribute to providing a new and highly effective treatment strategy for RSV and hMPV. More precisely, this projects aims to: (i) elucidate the precise molecular effects of small-molecule polymerase inhibitors of RSV and hMPV, (ii) study the mechanisms by which potential resistance may emerge against these inhibitors and (iii) contribute to the elucidation of the structures of the full-length RSV and hMPV polymerases by discovering conformation-stabilizing antibodies, that can be used in crystallization or cryo-EM approaches; and by measuring the extent of the stabilizing effects of these antibodies and small-molecule inhibitors, enabling optimized design of drug candidates. To do so, we will use, develop and exploit challenging and innovative techniques to find an effective treatment for RSV and hMPV infections.
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