RESUMO
A novel proprietary formulation, ViruSAL, has previously been demonstrated to inhibit diverse enveloped viral infections in vitro and in vivo. We evaluated the ability of ViruSAL to inhibit SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) infectivity, using physiologically relevant models of the human bronchial epithelium, to model early infection of the upper respiratory tract. ViruSAL potently inhibited SARS-CoV-2 infection of human bronchial epithelial cells cultured as an air-liquid interface (ALI) model, in a concentration- and time-dependent manner. Viral infection was completely inhibited when ViruSAL was added to bronchial airway models prior to infection. Importantly, ViruSAL also inhibited viral infection when added to ALI models post-infection. No evidence of cellular toxicity was detected in ViruSAL-treated cells at concentrations that completely abrogated viral infectivity. Moreover, intranasal instillation of ViruSAL to a rat model did not result in any toxicity or pathological changes. Together these findings highlight the potential for ViruSAL as a novel and potent antiviral for use within clinical and prophylactic settings.
Assuntos
Antivirais , COVID-19 , Humanos , Ratos , Animais , Antivirais/farmacologia , SARS-CoV-2 , Células Epiteliais , BrônquiosRESUMO
Some free fatty acids derived from milk and vegetable oils are known to have potent antiviral and antibacterial properties. However, therapeutic applications of short- to medium-chain fatty acids are limited by physical characteristics such as immiscibility in aqueous solutions. We evaluated a novel proprietary formulation based on an emulsion of short-chain caprylic acid, ViroSAL, for its ability to inhibit a range of viral infections in vitro and in vivo. In vitro, ViroSAL inhibited the enveloped viruses Epstein-Barr, measles, herpes simplex, Zika and orf parapoxvirus, together with Ebola, Lassa, vesicular stomatitis and severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) pseudoviruses, in a concentration- and time-dependent manner. Evaluation of the components of ViroSAL revealed that caprylic acid was the main antiviral component; however, the ViroSAL formulation significantly inhibited viral entry compared with caprylic acid alone. In vivo, ViroSAL significantly inhibited Zika and Semliki Forest virus replication in mice following the inoculation of these viruses into mosquito bite sites. In agreement with studies investigating other free fatty acids, ViroSAL had no effect on norovirus, a non-enveloped virus, indicating that its mechanism of action may be surfactant disruption of the viral envelope. We have identified a novel antiviral formulation that is of great interest for the prevention and/or treatment of a broad range of enveloped viruses, particularly those of the skin and mucosal surfaces.
Assuntos
Antivirais , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave , Vírus , Infecção por Zika virus , Zika virus , Animais , Antivirais/farmacologia , Lipídeos , Camundongos , Internalização do VírusRESUMO
BACKGROUND: A novel emulsion with efficacy as an agent for eliminating biofilms was selected. The aim of this study was to examine efficacy and effect of a formulation of ML:8 against commensal bacteria harvested from ex vivo human colonic tissues. METHODS: Mucosal sheets, obtained at the time of surgery, were exposed for 2 minutes to one of four solutions: Krebs-Hensleit (KH) solution, saline (NaCl; 0.9%), povidone iodine (1%), or ML:8 (2%); n = 4. Lumenal surfaces were swabbed for culture under aerobic or anaerobic conditions. Following treatment, each sheet was mounted in Ussing chambers and voltage clamped. Tissues were challenged with carbachol. Permeability coefficient (Papp) was determined using mannitol fluxes. At the end of each experiment, tissues were examined histologically. RESULTS: Similar colony forming units grew in aerobic and anaerobic conditions in both control and NaCl treated tissues. Iodine reduced and ML:8 virtually abolished viable bacteria. Basal electrophysiological parameters were not different between treatments. Transepithelial electrical resistance values did not differ between groups. All tissues responded to carbachol, although this was attenuated in iodine treated tissue. Papp values were slightly elevated in all treated tissues but this did not reach significance. Histopathological assessment revealed no overt damage to tissues. CONCLUSION: Brief exposure to ML:8 reduced culturable bacterial burden from human intestinal tissues harvested at the time of surgical resection. Such gnotobiotic tissues retain structural and functional integrity. This is a novel approach to reduce bacterial burden.