In silico targeting SARS-CoV-2 spike protein and main protease by biochemical compounds

Abstract

Since there is no general agreement on drug treatment of SARS-CoV-2, the search for a new drug capable of treating COVID-19 is of utmost priority. This study aims to dereplicate the chemical compounds of the methanol extract of Salvia officinalis and Artemisia dracunculus , and assay the inhibitory effect of these compounds as well as the previously dereplicated components of Zingiber officinale against SARS-CoV-2 in an in-silico study. A molecular networking (MN) technique was applied to find the chemical constituents of the extracts. Docking analysis was also used to find the binding affinity of dereplicated components from S. officinalis , A. dracunculus , and Z. officinale to COV-2-SP and M pro . 57 compounds were dereplicated from the MeOH extracts of S. officinalis and A. dracunculus which include the class of polyphenols, flavonoids, coumarins, phenylpropanoids, anthocyanins, and dihydrochalcones. Molecular docking analysis indicated a high affinity of about 27 compounds from three mentioned plants against studied targets. kaempferol 3-O-rutinoside, neodiosmin, and querciturone with docking score values of -10.575, -10.208, and − 9.904 Kcal/mol and k i values of 0.016606, 0.030921, and 0.051749, respectively were found to have the highest affinities against COV-2-SP. 2-phenylethyl beta-primeveroside, curcumin PE, and kaempferol 3-O-rutinoside also indicated the highest affinity against M pro with docking scores of -10.34, -10.126 and − 9.705 and k i values of 0.024726, 0.035529, and 0.072494, respectively. MN can be successfully used for the dereplication of metabolites from plant extracts. In addition, the in-silico binding energies introduced several inhibitors from Z. officinale , S. officinalis , and A. dracunculus for the treatment of SARS-CoV-2 disease. Supplementary Information The online version contains supplementary material available at 10.1007/s11756-021-00881-z.

Molecular Docking and Interaction Analysis of Propolis Compounds Against SARS-CoV-2 Receptor

“…Similar to another in-silico study about keampferol's potential to inhibit SARS-COV-2 M Pro , Kaempferol 3-O-rutinoside as an active compound from Salvia officinalis, Artamesia dracunculus, and Zingiber officinale becomes a top three of 27 active compounds from an in silico analysis with best binding affinity −9.705 kcal/mol against M Pro [34,35]. Meanwhile in Zothantluanga et al, Kaempferol 3-O-α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranoside as an active compound from Acacia pennata become a top three of 29 phyto compounds from an in-silico analysis with best binding affinity -7.2 kcal/mol to M Pro using Autodock Vina on PyRx 0.8.…”

Critical Review of Plant-Derived Compounds as Possible Inhibitors of SARS-CoV-2 Proteases: A Comparison with Experimentally Validated Molecules

“…Among the inhibitors of Mpro, there are also biflavonoids like ginkgetin, amentoflavone (didemethyl-ginkgetin), and isoginkgetin. It can be noticed from their names that their structures are very similar, as well as their IC 50 against Mpro with values of 2.98, 2.33, and 8.65 μM, respectively. 25 Even so, some of these flavonoids and biflavonoids, such as quercetin, amentoflavone, apigenin, and luteloin, which inhibit SARS-CoV-2 Mpro, were identified previously as inhibitors of the SARS-CoV Mpro.…”

Pharmaceutical Prospects of Curcuminoids for the Remedy of COVID-19: Truth or Myth

“…The COVID-19 virus entry into host cells is initiated by binding of S protein to the host cell surface ACE2 as its target receptor ( Yan et al, 2020 ), and the RBD is the virus–host binding spots ( Veeramachaneni et al, 2021 ). In silico simulation data exhibited that curcumin has a high binding affinity to the RBD and ACE2 ( Babaeekhou et al, 2021 ; Nag et al, 2021 ; Umashankar et al, 2021 ). The binding of amino acid residues to curcumin presented near the RBM of S1 protein, and some curcuminoids have stable interactions with key spot residues for the binding of ACE2 comprising the glycosylation site ( Babaeekhou et al, 2021 ), suggesting the potential efficacy of curcumin/curcuminoids in hindering the formation of S protein–ACE2 complex ( Jena et al, 2021 ).…”

“…In silico simulation data exhibited that curcumin has a high binding affinity to the RBD and ACE2 ( Babaeekhou et al, 2021 ; Nag et al, 2021 ; Umashankar et al, 2021 ). The binding of amino acid residues to curcumin presented near the RBM of S1 protein, and some curcuminoids have stable interactions with key spot residues for the binding of ACE2 comprising the glycosylation site ( Babaeekhou et al, 2021 ), suggesting the potential efficacy of curcumin/curcuminoids in hindering the formation of S protein–ACE2 complex ( Jena et al, 2021 ). A recent genome sequencing study also indicated that the spread of double mutations at E484Q/L452R, T478K/L452R, and F490S/L452Q of RBD has the latent potential for the enhancement of viral mutated S protein (S m ) and host ACE2 to form S m –ACE2 binding ( Aggarwal et al, 2021 ), and concurrently, that may cause more and effective infection of SARS-CoV-2 mutants.…”

“…Results of in silico studies show that curcumin/curcuminoids can form strong bonds with the active site of SARS-CoV-2 M pro ( Ibrahim et al, 2020 ; Bahun et al, 2022 ). Due to high binding affinity and its binding with the interface region of M pro may cause the protein conformational changes, indicating that curcumin/curcuminoids could be the potential ligands for COVID-19 therapy ( Ibrahim et al, 2020 ; Li and Kang 2020 ; Kumar M. et al, 2021 ; Mahmud et al, 2021a ; Babaeekhou et al, 2021 ; Teli et al, 2021 ; Halder et al, 2022 ). One more study demonstrated that demethoxycurcumin and bisdemethoxycurcumin had an optimum binding affinity with COVID-19 M pro by molecular modeling and showed the stable state by molecular dynamic (MD) simulation assay, suggesting these could be one of the potential ligands for COVID-19 therapy ( Mulu et al, 2021 ).…”