TY - JOUR

T1 - Natural Products from Marine Actinomycete Genus Salinispora Might Inhibit 3CLpro and PLpro Proteins of SARS-CoV-2: An In Silico Evidence

AU - Pokharkar, Omkar

AU - Zyryanov, Grigory

AU - Tsurkan, Mikhail

N1 - O.P. and G.V.Z. are thankful to the Ministry of Science and Education of RF (Agreement # 075-15-2022-1118 dated 29 June 2022) for funding.

PY - 2023

Y1 - 2023

N2 - Among the oldest marine species on the planet, the genus Salinispora is often encountered inhabiting sediments and other marine creatures in tropical and subtropical marine settings. This bacterial genus produces a plethora of natural products. The purpose of this study was to examine the potential for salinispora-based natural products (NPs) to combat the SARS-CoV-2 virus. The RCSB PDB was used to obtain the crystal structures of proteins 3CLpro and PLpro. All 125 NPs were obtained from online databases. Using Autodock Vina software v1.2.0 the molecular docking process was carried out after the proteins and ligands were prepared. Assessments of binding affinities and interacting amino acids were rigorously examined prior to MD simulations. The docking experiments revealed 35 NPs in total for both 3CLpro and PLpro, with high docking scores ranging from −8.0 kcal/mol to −9.0 kcal/mol. However, a thorough binding residue analyses of all docked complexes filtered nine NPs showing strong interactions with HIS: 41 and CYS: 145 of 3CLpro. Whereas, for PLpro, merely six NPs presented good interactions with residues CYS: 111, HIS: 272, and ASP: 286. Further research was conducted on residue–residue and ligand–residue interactions in both the filtered docked complexes and the Apo-protein structures using the Protein Contacts Atlas website. All complexes were found to be stable in CABS-flex 2.0 MD simulations conducted at various time frames (50, 125, 500, and 1000 cycles). In conclusion, salinaphthoquinone B appears to be the most promising metabolite, based on favorable amino acid interactions forming stable confirmations towards 3CLpro and PLpro enzymes, acting as a dual inhibitor. © 2023 by the authors.

AB - Among the oldest marine species on the planet, the genus Salinispora is often encountered inhabiting sediments and other marine creatures in tropical and subtropical marine settings. This bacterial genus produces a plethora of natural products. The purpose of this study was to examine the potential for salinispora-based natural products (NPs) to combat the SARS-CoV-2 virus. The RCSB PDB was used to obtain the crystal structures of proteins 3CLpro and PLpro. All 125 NPs were obtained from online databases. Using Autodock Vina software v1.2.0 the molecular docking process was carried out after the proteins and ligands were prepared. Assessments of binding affinities and interacting amino acids were rigorously examined prior to MD simulations. The docking experiments revealed 35 NPs in total for both 3CLpro and PLpro, with high docking scores ranging from −8.0 kcal/mol to −9.0 kcal/mol. However, a thorough binding residue analyses of all docked complexes filtered nine NPs showing strong interactions with HIS: 41 and CYS: 145 of 3CLpro. Whereas, for PLpro, merely six NPs presented good interactions with residues CYS: 111, HIS: 272, and ASP: 286. Further research was conducted on residue–residue and ligand–residue interactions in both the filtered docked complexes and the Apo-protein structures using the Protein Contacts Atlas website. All complexes were found to be stable in CABS-flex 2.0 MD simulations conducted at various time frames (50, 125, 500, and 1000 cycles). In conclusion, salinaphthoquinone B appears to be the most promising metabolite, based on favorable amino acid interactions forming stable confirmations towards 3CLpro and PLpro enzymes, acting as a dual inhibitor. © 2023 by the authors.

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U2 - 10.3390/microbiolres14040130

DO - 10.3390/microbiolres14040130

M3 - Article

VL - 14

SP - 1907

EP - 1941

JO - Microbiology Research

JF - Microbiology Research

SN - 2036-7473

IS - 4

ER -