Investigating the Role of Neuropilins in Facilitating Pan-Viral Infections

Viruses gain access to host cells through the specific recognition of biomolecules at the cell surface. My research focuses on neuropilins, a family of host-encoded surface receptors that recognise multibasic C-terminal motifs in circulating extracellular ligands. I recently demonstrated that the Spike glycoprotein of the pandemic coronavirus SARS-CoV-2 exhibits molecular mimicry to generate a sequence capable of binding to Neuropilin-1, thereby enhancing infection of human cells. Bioinformatic analysis suggests that a broad range of additional viral glycoproteins also generate putative neuropilin-binding motifs, including high-profile pathogens such as MERS-CoV, Influenza A virus, Ebolavirus and HIV-1. I will establish infection screens, utilising pseudotyped lentiviruses and authentic live viruses where appropriate, to directly test the role of neuropilins in facilitating infection of human cells by these pathogens. Through a network of collaborations, I will screen small molecule compounds to identify inhibitors of this infection process. This approach will be supported by biochemical characterisation of the molecular interfaces between viral glycoproteins and neuropilins, and investigation of the cell biological pathways that underpin this infection mechanism. Together, this interdisciplinary approach aims to clarify the role of neuropilins as 'pan-viral' therapeutic targets and potentially inform the development of antiviral compounds for the treatment of infectious diseases.