The dual role of phytochemicals on SARS-CoV-2 inhibition by targeting host and viral proteins

Abstract

Background The severe acute respiratory syndrome-2019 has affected more than 190 million people around the world and caused severe crises throughout the globe. Due to rapid mutation in the viral genome, it became important to simultaneously improvise the host immunity while targeting the viral protein to reduce the severity of the infection. Aim The current computational work focuses on multi-level rigorous screening of 47 medicinal plant-based phytochemicals for discovering effective phytochemical inhibitors against the host and viral targets. Experimental procedure A total of 586 phytochemicals were analyzed in detail based on their drug-likeness, pharmacological properties, and structure-based activity against the viral proteins (Spike glycoprotein, Papain-like protease, and Main protease) and host proteins (ACE2, Importin-subunit α-5, and β-1). Phytochemicals showing higher binding affinity with the dual capacity to target both the categories of proteins were further analyzed by profiling their chemical reactivity using Density-functional theory (DFT) based quantum chemical methods. Finally, detailed molecular dynamics simulations were performed to analyze the interactions of the complexes. Results and conclusion The results revealed that the selected phytochemicals from Andrographis paniculata , Aconitum heterophyllum , Costus speciosus and Inula racemosa may have the capacity to act with prominent affinity towards the host and viral proteins. Therefore, The Combination of active phytochemicals of these plants may prove to be more beneficial and can be used for developing the potential phytotherapeutic intervention.

Molecular modelling identification of phytocompounds from selected African botanicals as promising therapeutics against druggable human host cell targets of SARS-CoV-2

“…Although, the result of the binding energy suggests that the phytochemicals might be effective inhibitors of Cath L, however, the inhibition mechanism displayed by HPN and QOR may differ to that of BFA and MOG. Generally, the observations on the RMSD values and patterns for the druggable targets in this study are good indications of the test compounds as prospective drug candidates judging by their values which were <3.5 Å acceptable limit and agrees with a previous study [ 54 ], where plant secondary metabolites induced significant structural stability at the druggable sites of SARS-CoV-2.

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Chemistry of Protein-Phenolic Interactions Toward the Microbiota and Microbial Infections

“…Lastly, Singh et al (78) analyzed the binding affinity of 586 phytochemicals to the viral proteins (glycoprotein spike, Papain-protease, and protease main) and host proteins (ACE2, Importin-subunit a-5, and b-1). Their hydrogen bonds and hydrophobic interaction, as well as the binding energies and interactive amino acid residues, were categorized.…”

“…This means that the interaction by hydrogen bonds between hetisinone and ACE2 represented a strong interaction than the control drug molecule. The viral-host interaction was disturbed by HCQ binding to the ACE2 receptor (allosteric region), which can inhibit the viral penetration to the human cell (78).…”

Curcumin inhibits spike protein of new SARS-CoV-2 variant of concern (VOC) Omicron, an in silico study

“…Several phytochemicals were being tested by in silico methods that can act as potent drug components in treating SARS-CoV-2 infection [ 20 ] and proteins such as main protease and Spike protein were utilized as the drug targets [ 21 , 22 ]. However, Receptor Binding Domain (RBD) of the Spike protein is one of the most common targets for the inhibition of cellular entry of SARS-CoV-2 [ 11 , 23 ].…”