The hepatitis C virus (HCV) consists of eight genotypes and 90 subtypes, with genotype (GT) 3 being the second most common globally and is linked to higher incidences of steatosis and rapid development of fibrosis and cirrhosis. The NS3/4A serine protease, a heterodimer complex of two HCV non-structural proteins, is an effective target for pharmaceutical intervention due to its essential roles in processing HCV polyproteins and inhibiting innate immunity. This study combines structure-based virtual screening (SBVS) of predefined compound libraries, pharmacokinetic prediction (ADME/T) and in vitro evaluation to identify potential low molecular weight (<500 Dalton) inhibitors of the NS3/4A serine protease (GT3). In silico screening of ZINC and PubChem libraries yielded five selected compounds as potential candidates. Dose-dependent inhibition of the NS3/4A serine protease and HCV replication in HuH-7.5 cells revealed that compound A (PubChem ID No. 16672637) exhibited inhibition towards HCV GT3 with an IC50 of 106.7µM and EC50 of 25.8µM, respectively. Thus, compound A may be developed as a potent, low molecular weight drug against the HCV NS3/4A serine protease of GT3.

Ticks are vectors of bacteria, protozoa and viruses capable of causing serious and life threatening diseases in humans and animals. Disease transmission occurs through the transfer of pathogen from tick bites to susceptible humans or animals. Most commonly known tick-borne pathogens are obligate intracellular microorganisms but little is known on the prevalence of culturable pathogenic bacteria from ticks capable of growth on artificial nutrient media. One hundred and forty seven ticks originating from dairy cattle, goats and rodents were collected from nine selected sites in Peninsular Malaysia. The culture of surfacesterilized tick homogenates revealed the isolation of various pathogenic bacteria including, Staphylococcus sp., Corynebacterium sp., Rothia sp., Enterococcus faecalis, Klebsiella pneumoniae, Escherichia coli and Bacillus sp. and its derived genera. These pathogens are among those that affect humans and animals. Findings from this study suggest that in addition to the regular intracellular pathogens, ticks could also harbor extracellular pathogenic bacteria. Further studies, hence, would be needed to determine if these extracellular pathogens could contribute to human or animal infection.