ABSTRACT
In the three years since the first outbreak of COVID-19 in 2019, the SARS-CoV-2 virus has continued to be prevalent in our community. It is believed that the virus will remain present, and be transmitted at a predictable rate, turning endemic. A major challenge that leads to this is the constant yet rapid mutation of the virus, which has rendered vaccination and current treatments less effective. In this study, the Lactobacillus sakei Probio65 extract (P65-CFS) was tested for its safety and efficacy in inhibiting SARS-CoV-2 replication. Viral load quantification by RT-PCR showed that the P65-CFS inhibited SARS-CoV-2 replication in human embryonic kidney (HEK) 293 cells in a dose-dependent manner, with 150 mg/mL being the most effective concentration (60.16% replication inhibition) (p < 0.05). No cytotoxicity was inflicted on the HEK 293 cells, human corneal epithelial (HCE) cells, or human cervical (HeLa) cells, as confirmed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The P65-CFS (150 mg/mL) also reduced 83.40% of reactive oxidizing species (ROS) and extracellular signal-regulated kinases (ERK) phosphorylation in virus-infected cells, both of which function as important biomarkers for the pathogenesis of SARS-CoV-2. Furthermore, inflammatory markers, including interferon-α (IFN-α), IFN-ß, and interleukin-6 (IL-6), were all downregulated by P65-CFS in virus-infected cells as compared to the untreated control (p < 0.05). It was conclusively found that L. sakei Probio65 showed notable therapeutic efficacy in vitro by controlling not only viral multiplication but also pathogenicity; this finding suggests its potential to prevent severe COVID-19 and shorten the duration of infectiousness, thus proving useful as an adjuvant along with the currently available treatments.
ABSTRACT
The unprecedented health catastrophe derived from the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2 infection) met with a phenomenal scientific response across the globe. Worldwide, the scientific community was focused on finding a cure for the deadly disease. A wide range of research studies has consistently revealed the link between SARS-CoV-2 infection severity and abnormal gut microbiomes, suggesting its potential in developing novel therapeutic approaches. Probiotics have been extensively studied to promote health in human hosts and reestablish a balance in the dysbiotic gut microbiome; however, there is strong skepticism about their safety and efficacy. Consequently, the metabolic signatures of probiotics, often referred to as "postbiotics", could prove of paramount importance for adjuvant cures in patients with SARS-CoV-2. Postbiotics exhibit safety, enhanced shelf-life, and stability and, therefore, could be implemented in SARS-CoV-2 prophylactic strategies with no undue adverse side effects. The current study is a preliminary investigation of the antiviral properties of postbiotic metabolites derived from Leuconostoc mesenteroides GBUT-21. The study focuses on the potential biological role in inactivating SARS-CoV-2 and reducing related inflammatory pathways.
ABSTRACT
Major depression disorder (MDD) has become a common life-threatening disorder. Despite the number of studies and the introduced antidepressants, MDD remains a major global health issue. Carthamus tinctorius (safflower) is traditionally used for food and medical purposes. This study investigated the chemical profile and the antidepressant-like effect of the Carthamus tincto-rius hot water extract in male mice and its mechanism using a transcriptomic analysis. The antidepressant effect of hot water extract (50 mg/kg and 150 mg/kg) was investigated in mice versus the untreated group (saline) and positive control group (fluoxetine 10 mg/kg). Hippocampus transcriptome changes were investigated to understand the Carthamus tinctorius mechanism of action. The GC-MS analysis of Carthamus tinctorius showed that hot water extract yielded the highest amount of oleamide as the most active ingredient. Neuro-behavioral tests demonstrated that the safflower treatment significantly reduced immobility time in TST and FST and improved performance in the YMSAT compared to the control group. RNA-seq analysis revealed a significant differential gene expression pattern in several genes such as Ube2j2, Ncor1, Tuba1c, Grik1, Msmo1, and Casp9 related to MDD regulation in 50 mg/kg safflower treatment as compared to untreated and fluoxetine-treated groups. Our findings demonstrated the antidepressant-like effect of safflower hot water extract and its bioactive ingredient oleamide on mice, validated by a significantly shortened immobility time in TST and FST and an increase in the percentage of spontaneous alternation.
ABSTRACT
In response to the ongoing COVID-19 pandemic, the global effort to develop high efficacy countermeasures to control the infection are being conducted at full swing. While the efficacy of vaccines and coronavirus drugs are being tested, the microbiome approach represents an alternative pathophysiology-based approach to prevent the severity of the infection. In the current study, we evaluated the action of a novel probiotic Lactobacillus plantarum Probio-88 against SARS-COV-2 replication and immune regulation using an in vitro and in silico study. The results showed that extract from this strain (P88-CFS) significantly inhibited the replication of SARS-COV-2 and the production of reactive oxygen species (ROS) levels. Furthermore, compared with infected cells, P88-CFS treated cells showed a significant reduction in inflammatory markers such as IFN-α, IFN-ß, and IL-6. Using an in silico molecular docking approach, it was postulated that the antiviral activity of L. plantarum Probio-88 was derived from plantaricin E (PlnE) and F (PlnF). The high binding affinity and formation of hydrogen bonding indicated that the association of PlnE and PlnF on SARS-COV-2 helicase might serve as a blocker by preventing the binding of ss-RNA during the replication of the virus. In conclusion, our study substantiated that P88-CFS could be used as an integrative therapeutic approach along with vaccine to contain the spread of the highly infectious pathogen and possibly its variants.
ABSTRACT
Severe acute respiratory syndrome coronavirus (SARS-CoV-2) is responsible for the coronavirus disease- 2019 (COVID-19) pandemic, which was first reported from Wuhan, China, in late 2019. This infection spread to thousands of people globally within a short span of time with a progressive trend to mortality of citizens. Posing a potential public health threat, SARS-CoV-2 progressed from animal-to-human to human-tohuman transmission with symptoms ranging from little or no illness to persons being severely ill and many deaths, confirming two criteria for declaring COVID-19 a pandemic. The disease shows a progressive trend in symptomology, ranging from mild to severe pneumoniae to respiratory and multi-visceral failure that often leads to the death of patients with comorbidity within a short span of time. Intensive research efforts on different aspects of this human pathogen are underway across the globe for elucidating viral transmission routes and the mechanisms employed to overcome host defense responses. Due to the massive infective potential, studies are being carried out to develop effective diagnostics and therapeutic interventions, including re-purposing antivirals and other potential inhibitors. Herein, we describe the taxonomic classification of 'SARS-CoV-2', the structural organization of its genome, its infectivity, transmission, and receptor interaction; and we summarize risk assessment and approaches used for prevention of the infection. Finally, we discuss important aspects of the development of diagnostic tools and therapeutic countermeasures that have the potential to help in controlling the COVID-19 pandemic.