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Phytochemicals-based targeting RdRp and main protease of SARS-CoV-2 using docking and steered molecular dynamic simulation: A promising therapeutic approach for Tackling COVID-19

Parihar, Arpana ; Sonia, Zannatul Ferdous ; Akter, Farjana ; Ali, Md Ackas ; Hakim, Fuad Taufiqul ; Hossain, Md Shahadat

Computers in biology and medicine, 2022-06, Vol.145, p.105468-105468, Article 105468 [Periódico revisado por pares]

United States: Elsevier Ltd

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Phytochemicals-based targeting RdRp and main protease of SARS-CoV-2 using docking and steered molecular dynamic simulation: A promising therapeutic approach for Tackling COVID-19
Autor: Parihar, Arpana ; Sonia, Zannatul Ferdous ; Akter, Farjana ; Ali, Md Ackas ; Hakim, Fuad Taufiqul ; Hossain, Md Shahadat
Assuntos: Antiviral agents ; Binding ; Binding sites ; Biological activity ; Computer applications ; Coronaviruses ; COVID-19 ; COVID-19 Drug Treatment ; COVID-19 vaccines ; DNA-directed RNA polymerase ; Drug development ; Dynamic stability ; Economic impact ; Enzymes ; Humans ; Hydrogen bonds ; Ligands ; Main proteases ; Molecular docking ; Molecular Docking Simulation ; Molecular dynamic simulation ; Molecular dynamics ; Molecular Dynamics Simulation ; Pandemics ; Peptide Hydrolases - metabolism ; Phytochemicals ; Phytochemicals - pharmacology ; Protease ; Protease Inhibitors - chemistry ; Protease Inhibitors - pharmacology ; Proteinase ; Proteins ; RdRp ; RNA polymerase ; RNA-Dependent RNA Polymerase ; RNA-directed RNA polymerase ; SARS-CoV-2 ; Severe acute respiratory syndrome ; Severe acute respiratory syndrome coronavirus 2 ; Side effects ; Simulation ; Software ; Steered dynamic simulation ; Vaccines ; Viral diseases ; Viruses
É parte de: Computers in biology and medicine, 2022-06, Vol.145, p.105468-105468, Article 105468
Descrição: The ongoing COVID-19 pandemic has affected millions of people worldwide and caused substantial socio-economic losses. Few successful vaccine candidates have been approved against SARS-CoV-2; however, their therapeutic efficacy against the mutated strains of the virus remains questionable. Furthermore, the limited supply of vaccines and promising antiviral drugs have created havoc in the present scenario. Plant-based phytochemicals (bioactive molecules) are promising because of their low side effects and high therapeutic value. In this study, we aimed to screen for suitable phytochemicals with higher therapeutic value using the two most crucial proteins of SARS-CoV-2, the RNA-dependent RNA polymerase (RdRp) and main protease (Mpro). We used computational tools such as molecular docking and steered molecular dynamics simulations to gain insights into the different types of interactions and estimated the relative binding forces between the phytochemicals and their respective targets. To the best of our knowledge, this is the first report that not only involves a search for a therapeutic bioactive molecule but also sheds light on the mechanisms underlying target inhibition in terms of calculations of force and work needed to extractthe ligand from the pocket of its target. The complexes showing higher binding forces were subjected to 200 ns molecular dynamic simulations to check the stability of the ligand inside the binding pocket. Our results suggested that isoskimmiwallin and terflavin A are potential inhibitors of RdRp, whereas isoquercitrin and isoorientin are the lead molecules against Mpro. Collectively, our findings could potentially aid in the development of novel therapeutics against COVID-19. [Display omitted] •Phytochemicals-based Targeting against RdRp and Main Protease of SARS-CoV-2.•High-throughput virtual screening followed by steered molecular dynamic simulations was done. .•The SMD, ADMET and 200ns MD simulation of lead complexes revealed Isoskimmiwallin and tarflavin A against RdRp, whereas Isoquercitine and Isoorientin as lead molecules against Mpro.
Editor: United States: Elsevier Ltd
Idioma: Inglês

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Phytochemicals-based targeting RdRp and main protease of SARS-CoV-2 using docking and steered molecular dynamic simulation: A promising therapeutic approach for Tackling COVID-19

Parihar, Arpana ; Sonia, Zannatul Ferdous ; Akter, Farjana ; Ali, Md Ackas ; Hakim, Fuad Taufiqul ; Hossain, Md Shahadat

United States: Elsevier Ltd

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