The Inhibition of SARS-CoV-2 and the Modulation of Inflammatory Responses by the Extract of Lactobacillus sakei Probio65

Irfan A Rather; Lee-Ching Lew; Majid Rasool Kamli; Khalid Rehman Hakeem; Jamal S M Sabir; Yong-Ha Park; Yan-Yan Hor

doi:10.3390/vaccines10122106

The Inhibition of SARS-CoV-2 and the Modulation of Inflammatory Responses by the Extract of Lactobacillus sakei Probio65

Vaccines (Basel). 2022 Dec 9;10(12):2106. doi: 10.3390/vaccines10122106.

Authors

Irfan A Rather^{1

2}, Lee-Ching Lew³, Majid Rasool Kamli^{1

2}, Khalid Rehman Hakeem^{1

4

5}, Jamal S M Sabir^{1

2}, Yong-Ha Park^{3

6

7}, Yan-Yan Hor³

Affiliations

¹ Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
² Center of Excellence in Bionanoscience Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
³ Probionic Corporation Jeonbuk Institute for Food-Bioindustry, 111-18, Wonjangdong-gil, Deokjin-gu, Jeonju-si 54810, Republic of Korea.
⁴ Princess Dr. Najla Bint Saud Al-Saud Center for Excellence Research in Biotechnology, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
⁵ Department of Public Health, Daffodil International University, Dhaka 1341, Bangladesh.
⁶ Department of Biotechnology, Yeungnam University, 280 Daehak-Ro, Gyeongsan 38541, Republic of Korea.
⁷ PYH Lab, Yeungnam University, 280 Daehak-Ro, Gyeongsan 38541, Republic of Korea.

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.

Keywords: COVID-19; ERK; Lactobacillus sakei; PROBIO65; ROS; SARS-CoV-2; inflammatory; viral replication.

Grants and funding

This project was funded by the Deanship of Scientific Research (DSR), King Abdulaziz University, Jeddah, under the grant no. GCV19-27-1441. The authors, therefore, acknowledge with thanks the DSR technical and financial support.