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 agai...
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Elsevier
2025-06-01
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| Series: | Aspects of Molecular Medicine |
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| author | Manisha Mandal Shyamapada Mandal |
| author_facet | Manisha Mandal Shyamapada Mandal |
| author_sort | Manisha Mandal |
| collection | DOAJ |
| description | 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 (KD, M) using PRODIGY. Pln-JK had excellent interaction with NSP1 displaying binding affinity of 9.1 kcal/mol and KD value of 2.1 × 10−7. The binding affinity and KD 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. |
| format | Article |
| id | doaj-art-77fce2e91c794f1c85e9322e1865ce3a |
| institution | DOAJ |
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| language | English |
| publishDate | 2025-06-01 |
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| series | Aspects of Molecular Medicine |
| spelling | doaj-art-77fce2e91c794f1c85e9322e1865ce3a2025-08-20T03:03:08ZengElsevierAspects of Molecular Medicine2949-68882025-06-01510008010.1016/j.amolm.2025.100080Evaluation of inhibitory efficacy of plantaricin JK against NSP1 from SARS-CoV-2 by in silico methodsManisha Mandal0Shyamapada Mandal1Department of Physiology, MGM Medical College, Kishanganj, Bihar, PIN-855107, IndiaDepartment of Zoology, University of Gour Banga, West Bengal, Malda, PIN-732103, India; Corresponding author.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 (KD, M) using PRODIGY. Pln-JK had excellent interaction with NSP1 displaying binding affinity of 9.1 kcal/mol and KD value of 2.1 × 10−7. The binding affinity and KD 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.http://www.sciencedirect.com/science/article/pii/S2949688825000188SARS-CoV-2Non-structural protein-1Plantaricin JKPeptide 5Molecular dockingMolecular dynamic simulation |
| spellingShingle | Manisha Mandal Shyamapada Mandal Evaluation of inhibitory efficacy of plantaricin JK against NSP1 from SARS-CoV-2 by in silico methods Aspects of Molecular Medicine SARS-CoV-2 Non-structural protein-1 Plantaricin JK Peptide 5 Molecular docking Molecular dynamic simulation |
| title | Evaluation of inhibitory efficacy of plantaricin JK against NSP1 from SARS-CoV-2 by in silico methods |
| title_full | Evaluation of inhibitory efficacy of plantaricin JK against NSP1 from SARS-CoV-2 by in silico methods |
| title_fullStr | Evaluation of inhibitory efficacy of plantaricin JK against NSP1 from SARS-CoV-2 by in silico methods |
| title_full_unstemmed | Evaluation of inhibitory efficacy of plantaricin JK against NSP1 from SARS-CoV-2 by in silico methods |
| title_short | Evaluation of inhibitory efficacy of plantaricin JK against NSP1 from SARS-CoV-2 by in silico methods |
| title_sort | evaluation of inhibitory efficacy of plantaricin jk against nsp1 from sars cov 2 by in silico methods |
| topic | SARS-CoV-2 Non-structural protein-1 Plantaricin JK Peptide 5 Molecular docking Molecular dynamic simulation |
| url | http://www.sciencedirect.com/science/article/pii/S2949688825000188 |
| work_keys_str_mv | AT manishamandal evaluationofinhibitoryefficacyofplantaricinjkagainstnsp1fromsarscov2byinsilicomethods AT shyamapadamandal evaluationofinhibitoryefficacyofplantaricinjkagainstnsp1fromsarscov2byinsilicomethods |