Supramolecular cylinders target bulge structures in the 5-prime UTR of the RNA genome of SARS-CoV-2 and inhibit viral replication

The untranslated regions (UTRs) of viral genomes contain a variety of conserved yet dynamic structures crucial for viral replication, providing drug targets for the development of broad spectrum anti-virals. We combine in vitro RNA analysis with Molecular Dynamics simulations to build the first 3D models of the structure and dynamics of key regions of the 5 UTR of the SARS-CoV-2 genome. Furthermore, we determine the binding of metallo-supramolecular helicates (cylinders) to this RNA structure. These nano-size agents are uniquely able to thread through RNA junctions and we identify their binding to a 3-base bulge and the central cross 4-way junction located in the stem loop 5. Finally, we show these RNA-binding cylinders suppress SARS-CoV-2 replication, highlighting their potential as novel antiviral agents.

The hyperlipidaemic drug fenofibrate significantly reduces infection by SARS-CoV-2 in cell culture models

The SARS-CoV-2 pandemic has caused a significant number of fatalities and worldwide disruption. To identify drugs to repurpose to treat SARS-CoV-2 infections, we established a screen to measure dimerization of ACE2, the primary receptor for the virus. This screen identified fenofibric acid, the active metabolite of fenofibrate. Fenofibric acid also destabilized the receptor binding domain (RBD) of the viral spike protein and inhibited RBD binding to ACE2 in ELISA and whole cell binding assays. Fenofibrate and fenofibric acid were tested by two independent laboratories measuring infection of cultured Vero cells using two different SARS-CoV-2 isolates. In both settings at drug concentrations which are clinically achievable, fenofibrate and fenofibric acid reduced viral infection by up to 70%. Together with its extensive history of clinical use and its relatively good safety profile, these studies identify fenofibrate as a potential therapeutic agent requiring urgent clinical evaluation to treat SARS-CoV-2 infection. TeaserThe approved drug fenofibrate inhibits infection by SARS-COV-2

Formulation of a composite nasal spray enabling enhanced surface coverage and prophylaxis of SARS-COV-2

Airborne pathogens pose high risks in terms of both contraction and transmission within the respiratory pathways, in particular the nasal region. Although knowledge of airborne transmission has long been known, there is little in the way of adequate intervention that can protect the individual, or even prevent further spread. This study focuses on a nasal applicant with the capacity to combat such issues, by focussing on the SARS-CoV-2 virus. Formulation of a spray containing polysaccharides known for their mucoadhesive properties was undertaken and characterised for their mechanical, spray patterns and antiviral properties. The ability to engineer key behaviours such as yielding have been shown, through systematic understanding of a composite mixture containing two polymers: gellan and {lambda}carrageenan. Furthermore, spray systems demonstrated highly potent antiviral capacities, resulting in complete inhibition of the virus when studied for both prophylaxis and prevention of spread. Finally, a mechanism has been proposed to explain such findings. Therefore, demonstrating the first fully preventative device, targeted to protect the lining of the upper respiratory pathways.