The coronavirus disease 2019 (COVID-19) rapidly spread across the globe, infecting millions and causing hundreds of deaths. It has been now around three years but still, it remained a serious threat worldwide, even after the availability of some vaccines. Bio-surfactants are known to have antiviral activities and might be a potential alternative for the treatment of SARS-CoV-2 infection. In the present study, we have isolated and purified, a surfactin-like lipopeptide produced by a probiotic bacterial strain Bacillus clausii TS. Upon purification and characterization with MALDI analysis, the molecular weight of the lipopeptide is confirmed as 1037 Da (similar to surfactin C) which is known to have antiviral activities against various enveloped viruses. Purified surfactin-like lipopeptide showed efficient binding and inhibition of SARS-CoV-2 spike (S1) protein, revealed by competitive ELISA assay. Further, we have explored the complete thermodynamics of the inhibitory binding of surfactin-like lipopeptide with S1 protein using isothermal titration calorimetric (ITC) assay. ITC results are in agreement with ELISA with a binding constant of 1.78 × 10^-4 M^-1. For further validation of the inhibitory binding of surfactin-like lipopeptide with S1 protein and its receptor binding domain (RBD), we performed molecular docking, dynamics, and simulation experiments. Our results suggested that surfactin could be a promising drug agent for the spike protein targeting drug development strategy against SARS-CoV-2 and other emerging variants.Communicated by Ramaswamy H. Sarma.

2022-02-01·Inflammation2区 · 医学

The Influence of Macrophage-Activating Lipopeptide-2 in Regard to Liver-Specific Changes Within a Murine Two-Hit Model

2区 · 医学

Article

作者: Shi, Yulong ; Wang, Weikang ; Xu, Ding ; Hildebrand, Frank ; Greven, Johannes ; Luo, Peng ; Tschernig, Thomas ; Horst, Klemens

Trauma hemorrhage (TH) and subsequent sepsis are well known to frequently result in severe organ damage. Although macrophage-activating lipopeptide-2 (MALP-2) has been described to exert beneficial effects on organ damage, and further clinical course after both isolated trauma and sepsis, little is known about the impact of MALP-2 in a clinically realistic two-hit scenario of TH and subsequent sepsis. As the liver represents a key organ for the posttraumatic immune response and development of complications, the effects of MALP-2 on the posttraumatic hepatic immunologic response and tissue damage were investigated in a murine "two-hit" model. In C57BL/6 mice, blood pressure-controlled (35 ± 5 mm Hg) TH was induced. Cecal ligation and puncture (CLP) was performed 48 h after TH. Mice were divided into two control groups (control 1, TH and laparotomy without CLP; control 2, TH and CLP) and three experimental groups (TH + CLP) treated with MALP-2 at different timepoints (ETH, end of TH; ECLP, end of CLP; 6CLP, 6 h after CLP). The observation time lasted for 168 h after induction of TH. Kupffer cells (KC) were isolated and cultured, and MPO activity was analyzed. Cell culture supernatants were taken for cytokine analysis (TNF-α, IL-6, MCP-1, GM-CSF, IL-10). Histological analysis was performed using the Hepatic Injury Severity Scoring (HISS). Statistical evaluation was carried out using SPSS (version 24.0.0; IBM, Armonk, NY, USA). MPO activity of control 1 group was lowest compared with all the other groups (p < 0.01). MPO activity of control 2 group was significantly higher than that in all experimental groups (ETH (p < 0.01), ECLP (p < 0.01), and 6CLP (p = 0.03)). Within the experimental groups, MPO activity was significantly reduced in the ETH (p = 0.04) and the ECLP (p < 0.01) groups compared with the 6CLP group. Moreover, ETH was also associated with the most pronounced reduction of cytokine expression by KC (p < 0.05). HISS revealed the largest damage in the group control 2. TH and subsequent sepsis lead to a distinct immunologic reaction in the liver with an increase of cytokine expression of KC and pronounced infiltration of granulocytes with associated severe tissue damage. MALP application decreases the hepatic immune response and liver damage, with the most pronounced effects if applied at the end of TH.

2021-01-01·Annals of Anatomy - Anatomischer Anzeiger3区 · 医学

Macrophage activating lipopeptide 2 is effective in mycobacterial lung infection

3区 · 医学

Article

作者: Pabst, Reinhard ; Tschernig, Thomas

MALP-2, a synthetic lipopeptide is a Toll-like receptor 2 and -6 ligand and agonist. MALP-2 stimulates immune cells at different sites. Local stimulation in the lungs has beneficial effects in experimental pneumococci infection. The presented study investigated local effects of MALP-2 in the mycobacterial infection of lungs. MALP-2 was applied prior, simultaneously or after the pulmonary infection with Mycobacterium bovis BCG. Colony forming units were determined in the bronchoalveolar lavage fluid and lung homogenate. Numbers of Mycobacterium bovis BCG colony forming units were found to be reduced in two compartments, bronchoalveolar lavage fluid and lung homogenate after treatment with MALP-2 simultaneously to the infection for up to eight weeks. Reduction of the bacterial load in both compartments was also found up to two weeks after local treatment before and after the infection. Thus, macrophage activating lipopeptide-2 enhances the host defence in the lung in acute and long term bacterial infections.

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