The common cold is an annoying, uncomfortable and inevitable 2 weeks of your year. Colds don’t only cause problems on a personal level, but the millions of lost work hours also cause an economic impact. They are caused by human rhinoviruses, the most known species of which are RV-A and RV-B.
Past research into combating these variant types have proved successful in lab cultures, targeting the protomer canyons, or “pocket” features. These are capsid grooves characteristic of Enteroviruses, and have residues conferring receptor recognition. Capsid-binding antivirals fit into these pockets and attach to the receptors, creating subdivided virus-drug complexes with pore like openings giving an entrance for the drug. Pleconaril for instance is reported to be 93% effective against these species.
These complexes are roughly divided into two groups along the species divide, with differing canyon types.
However in 2006 a third species was discovered – RV-C. This species grows in under broader conditions than its counter parts, is less receptive to drugs, and worryingly found to cause half of cold infections in young children. This species avoided detection as it doesn’t propagate in typical cell culture systems. The 51 types recognised were discovered by direct sequencing from patient effluents!
Alternative attempts at culturing RV-C through fledgling studies using differentiated sinus and brachial epithelial cells at air-liquid interface (ALI) are promising. The only other study uses mucus membranes in primary human donor samples, which are few and far between! Also the variety of donors makes this technique variable and somewhat unreliable.
Both however don’t produce enough RV-C for biological research, so most information on the species comes from comparative studies with the wider known RV-A and RV-B species.
Holly Basta and co authors of this paper have used past genome alignments in combination with superimposed determined capsid structures of RV-A and RV-B types to create a high resolution 3-D model for The RV-C species. The model shows the vital Cα backbone present in viral components of RV-C, meaning the RV-C drug-binding “pocket” is superimposable on the RV-A and RV-B structures.
This structural model was termed C15, an isolate cloned into cDNA and tested for biological activity by mucus and ALI techniques.
The model showed C15 to have an altered surface structure to RV-A and RV-B. This accounted for it’s resistance to drugs engineered for RV-A and RV-B species, as it has different residues and receptors within the “pocket” structure.
Computer models found Pleconaril and some other drugs did fit into C15s’ “pocket”, but the diversity of residues in the viral “pocket” mean in practice these drugs are of no affect to viral growth. The authors commented they may at best find an alternate route “wiggling through tenaciously, despite the altered sequences”.
This will call for a RV-C specific drug in combination with the former RV-A and RV-B drugs, a path that will be eased significantly by the plethora of work already conducted studying RV-A and RV-B. Obviously much more research is needed in order to develop such a drug, but this model is significant in that it is a huge step in that direction, and can provide a basis for future tests and drug models.
- Basta, H. A., Ashraf, S., Sgro, J. Y., Bochkov, Y. A., Gern, J. E., & Palmenberg, A. C. (2014). Modeling of the human rhinovirus C capsid suggests possible causes for antiviral drug resistance. Virology, 448, 82-90.