05) in gingival bleeding was seen with a therapeutic ARRY-438162 in vitro dose of 0.06 U krill enzymes compared with placebo chewing gum [41]. The gum containing proteolytic enzymes was found to be well tolerated as none of the subjects reported any adverse reactions or events during the entire trial
period. Viral Infections Acute nasopharyngitis, or the common cold, caused by any one of a large number of antigenically distinct viruses and as one of the most common infectious syndromes in humans, is associated with significant health burden, both in terms of financial and quality of life outcomes [42, 43]. Pathogens of the enterovirus family (human rhinoviruses and Coxsackie A virus serotypes) are the principal causative agent in viral infections Selleck SB202190 and can result in symptoms such as sore throat, sneezing and rhinorrhea, and secondary bacterial infections, as well as more severe symptoms by exacerbating asthma, chronic obstructive pulmonary disease, and cystic fibrosis [42, 43]. Rhinovirus, the most common cause of colds and acute respiratory tract illness [34], gains entry into
host cells of the nose and throat by interacting with the human intercellular adhesion molecule 1 (or CD54) [15]. This suggests that proteases that target these molecules, such as those from cod L-gulonolactone oxidase trypsin [28], may have therapeutic potential in the management of viral infections. Indeed, in vitro studies have shown that
exposing viruses to trypsins results in a reduction in infectivity/activation [44, 45]. Furthermore, data from postmarket studies suggest that the use of ColdZyme® (Enzymatica AB, Lund, Selleck ICG-001 Sweden) mouth spray, an oral solution containing glycerol and a cold-adapted cod trypsin, can reduce the incidence of the common cold [46]. Marketed for use as a moisturizer and to improve oral hygiene, users of ColdZyme noted a reduced occurrence of cold symptoms. The ColdZyme mouth spray creates a thin film in the mouth and throat cavity that acts as an active surface barrier with proteolytic activity. Furthermore, the cold-adapted trypsin used in ColdZyme mouth spray has shown high efficiency in reducing the infectivity of human rhinovirus 16 [46] and herpes simplex virus 1 in vitro [47]. A summary of the proteases can be found in Table 1 [2, 3, 11–13, 38, 39, 41, 46, 47].