Surfactin-like lipopeptides from Bacillus clausii efficiently bind to spike glycoprotein of SARS-CoV-2

Abstract

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

Keywords:

• Surfactin
• lipopeptide
• spike protein
• molecular dynamics simulations
• SARS-CoV-2
• COVID-19

Acknowledgments

PB is thankful to the Department of Radiation Oncology, University of Missouri, Columbia, USA, for providing the space for this work. SMM acknowledges the Department of Biotechnology, Indian Institute of Technology, Kharagpur, India, and ABGENEX Private Limited, India, for gifting the proteins and antibodies.

Author contribution

PB, TC, DR, and MM wrote the manuscript and performed the experiments. PB, DR, and TC prepared the figures and illustrations. SMM conceived the original idea and supervised the work.

Disclosure statement

Authors declare no conflict of interest.

Additional information

Funding

Present work is not supported by any funding source.