Non-coding regions of viral RNA (vRNA) genomes are critically important in the regulation of gene expression. In particular, pseudoknot (PK) structures, which are present in a wide range of RNA molecules, have a variety of roles. The 5′ untranslated region (5′ UTR) of foot-and-mouth disease virus (FMDV) vRNA is considerably longer than in other viruses from the picornavirus family and consists of a number of distinctive structural motifs that includes multiple (2, 3 or 4 depending on the virus strain) putative PKs linked in tandem. The role(s) of the PKs in the FMDV infection are not fully understood. Here, using bioinformatics, sub-genomic replicons and recombinant viruses we have investigated the structural conservation and importance of the PKs in the FMDV lifecycle. Our results show that despite the conservation of two or more PKs across all FMDVs, a replicon lacking PKs was replication competent, albeit at reduced levels. Furthermore, in competition experiments, GFP FMDV replicons with less than two (0 or 1) PK structures were outcompeted by a mCherry FMDV wt replicon that had 4 PKs, whereas GFP replicons with 2 or 4 PKs were not. This apparent replicative advantage offered by the additional PKs correlates with the maintenance of at least two PKs in the genomes of FMDV field isolates. Despite a replicon lacking any PKs retaining the ability to replicate, viruses completely lacking PK were not viable and at least one PK was essential for recovery of infections virus, suggesting a role for the PKs in virion assembly. Thus, our study points to roles for the PKs in both vRNA replication and virion assembly, thereby improving understanding the molecular biology of FMDV replication and the wider roles of PK in RNA functions.

Acute gastroenteritis (AGE) is the highest cause of mortality worldwide in children under the age of 5 years, with the highest mortalities occurring in low-to-middle income countries. Treatment can involve use of unregulated herbal medication and antibiotics. A cross sectional study was carried out to investigate the use of antibiotics and traditional herbal medications in the management of AGE among Yòrùbá-speaking communities in Kwara State, Nigeria. Our findings suggest habitual use of antibiotics (54.6%) and herbal medication (42.5%) in the management of AGE with high levels of self-prescription of antibiotics (21.7%) and herbal medications (36.2%) within the community. Ethanolic extracts of selected herbal plants reported (i.e. Aristolochia ringens, Azadirachta indica, Chromolaena odorata, Etanda Africana, Ficus capensis, Ficus vogelii, Mangifera indica, Momordica charantia, Ocimum gratisimum, Senna alata, Sorghum bicolor and Vernonia amygdalina) were investigated for antibacterial properties, using bacteria known to be causative agents of AGE. Our findings showed that, with exception of Ficus vogelii, which enhanced bacterial growth, the plant extracts reported all showed some antibacterial activity. We further discuss our findings within a regulatory context, with the aim to guide the use of traditional and herbal medication in low-to medium income countries (LMICs) and reduce the potential risks associated with the development of antimicrobial resistance.