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The Inhibition of SARS-CoV-2 and the Modulation of Inflammatory Responses by the Extract of Lactobacillus sakei
Irfan A Rather1,2, Lee-Ching Lew3, Majid Rasool Kamli1,2
1Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
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.
Insights
Lactobacillus sakei Probio65 extract (P65-CFS) effectively inhibited SARS-CoV-2 replication and reduced viral pathogenicity in vitro. This probiotic extract shows potential as an adjuvant therapy to combat severe COVID-19 and reduce infectiousness.
Area of Science:
- Microbiology and Virology
- Immunology
- Cell Biology
Background:
- The SARS-CoV-2 virus continues to mutate, challenging the effectiveness of current COVID-19 vaccines and treatments.
- The virus is expected to become endemic, necessitating novel therapeutic strategies.
- Understanding viral replication and pathogenicity mechanisms is crucial for developing new interventions.
Purpose of the Study:
- To evaluate the safety and efficacy of Lactobacillus sakei Probio65 extract (P65-CFS) against SARS-CoV-2 replication.
- To investigate the impact of P65-CFS on viral load, cytotoxicity, and key biomarkers of SARS-CoV-2 infection.
- To explore the potential of P65-CFS as an adjuvant therapy for COVID-19.
Main Methods:
- Viral load was quantified using RT-PCR in human embryonic kidney (HEK) 293 cells treated with P65-CFS.
- Cytotoxicity was assessed using the MTT assay on HEK 293, human corneal epithelial (HCE), and human cervical (HeLa) cells.
- Reactive oxidizing species (ROS), extracellular signal-regulated kinases (ERK) phosphorylation, and inflammatory markers (IFN-α, IFN-ß, IL-6) were measured.
Main Results:
- P65-CFS demonstrated dose-dependent inhibition of SARS-CoV-2 replication, with 150 mg/mL achieving 60.16% inhibition (p < 0.05).
- No cytotoxicity was observed in any of the tested cell lines.
- P65-CFS significantly reduced ROS (83.40%), ERK phosphorylation, and downregulated inflammatory markers (IFN-α, IFN-ß, IL-6) in infected cells.
Conclusions:
- L. sakei Probio65 extract exhibits significant in vitro therapeutic efficacy against SARS-CoV-2.
- P65-CFS effectively controls viral multiplication and reduces key pathogenicity markers.
- These findings suggest P65-CFS as a potential adjuvant therapy to prevent severe COVID-19 and shorten infectious periods.
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