Evaluation of inhibitory efficacy of plantaricin JK against NSP1 from SARS-CoV-2 by in silico methods

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the causative agent of the COVID-19 pandemic, is still a cause of global concern, and therefore, safe and effective treatment is desperately needed. Bacteriocins produced by probiotic microorganisms displayed therapeutic potentiality against infectious diseases, including COVID-19. NSP1 (non-structural protein-1) of SARS-CoV-2 acts as a host translation inhibitor and reduces host immune function, thereby increasing viral pathogenicity and virulence. This information encouraged us to evaluate the inhibitory role of plantaricin JK (Pln-JK) against SARS-CoV-2 NSP1 using in silico methods. Herein, we used PatchMAN and CABS-dock webtools to perform molecular docking between SARS-CoV-2 NSP1 and Pln-JK, which generated NSP1-Pln-JK models. We used a peptide antiviral, peptide 5 (PEP5) as a reference. The top models (based on the lowest binding score and cluster density) of both systems were subjected to predict the binding affinity (ΔG, kcal/mol) and dissociation constant (K D , M) using PRODIGY. Pln-JK had excellent interaction with NSP1 displaying binding affinity of 9.1 kcal/mol and K D value of 2.1 × 10 −7 . The binding affinity and K D values for NSP1-PEP5 were −7.2 kcal/mol and 4.8 × 10 −6 M (for PatchMan complex) and −5.9 kcal/mol and 4.8 × 10 −5 M (for CABS-dock complex), respectively. HawkDock-based MM-GBSA binding free energies of CABS-dock and PatchMAN-generated complexes were −59.74 and −77.49 kcal/mol (for NSP1-Pln-JK) and −37.83 and −44.25 kcal/mol (for NSP1-PEP5), respectively. Further, molecular dynamic simulations-based MM-PBSA binding free energy confirmed NSP1-Pln-JK complex (−31.89 ± 0.91 kcal/mol) to be thermodynamically more stable than NSP1-PEP5 complex (−24.94 ± 0.6 kcal/mol). Pln-JK was predicted as non-allergic and non-toxic and thus emerged as a safe and effective molecule to combat SARS-CoV-2 infection. However, preclinical and clinical studies are needed before it can be considered as a prescription drug for the treatment of COVID-19. • Efficacy of bacteriocin has been predicted against SARS-CoV-2. • Molecular docking showed SARS-CoV-2 NSP1 inhibition by Plan-JK. • NSP1-Plan-JK was more stable than NSP1-PEP5 by MM-GB(PB)SA binding free energy. • Plan-JK has been predicted as non-allergic and non-toxic. • Peptide based drug may be safer and effective for COVID-19 treatment.