Catechin and curcumin interact with S protein of SARS-CoV2 and ACE2 of human cell membrane: insights from computational studies

Abstract

The recent outbreak of the coronavirus (SARS-CoV2) is an unprecedented threat to human health and society across the globe. In this context, development of suitable interventions is the need of the hour. The viral spike protein (S Protein) and the cognate host cell receptor ACE2 can be considered as effective and appropriate targets for interventions. It is evident from the present computational study, that catechin and curcumin, not only exhibit strong binding affinity to viral S Protein and host receptor ACE2 but also to their complex (receptor-binding domain (RBD) of the spike protein of SARS-CoV2 and ACE2; RBD/ACE2-complex). The binding affinity values of catechin and curcumin for the S protein, ACE2 and RBD/ACE2-complex are − 10.5 and − 7.9 kcal/mol; − 8.9 and − 7.8 kcal/mol; and − 9.1 and − 7.6 kcal/mol, respectively. Curcumin directly binds to the receptor binding domain (RBD) of viral S Protein. Molecular simulation study over a period of 100 ns further substantiates that such interaction within RBD site of S Protein occurs during 40–100 ns out of 100 ns simulation trajectory. Contrary to this, catechin binds with amino acid residues present near the RBD site of S Protein and causes fluctuation in the amino acid residues of the RBD and its near proximity. Both catechin and curcumin bind the interface of ‘RBD/ACE2-complex’ and intervene in causing fluctuation of the alpha helices and beta-strands of the protein complex. Protein–protein interaction studies in presence of curcumin or catechin also corroborate the above findings suggesting the efficacy of these two polyphenols in hindering the formation of S Protein-ACE2 complex. In conclusion, this computational study for the first time predicts the possibility of above two polyphenols for therapeutic strategy against SARS-CoV2.

8-Hydroxydihydrosanguinarine (8-HDS), a pyridone containing analogue of sanguinarine, can be a potential inhibitor of S protein and M protease of SARS CoV2: Insights from computational studies

“…Therefore, MD simulations prove to be effective in studying atomic level interactions and establishing the ligand selectivity towards the target. 8-HDS possesses the capability to fluctuate the RBD site of S protein, which interacts with ACE2 receptor of human cell for the viral infection [20].…”

“…The entry of SARS-CoV-2 into host cells is mediated through the binding of glycoproteinous spike protein of the virus, the S protein and host cell membrane receptor, i.e. Angiotensin Converting Enzyme 2 (ACE2) [20] (Fig. S1).…”

“…Lu et al, 2020 have suggested that receptor binding domain (RBD) of S-glycoprotein of SARS-CoV2 being similar to that of SARS-CoV, targets Angiotensin Converting Enzyme 2 (ACE2), a monomeric membrane bound receptor on human cells [21]. Hence, it is presumed that blocking the RBD site of the spike protein would prevent viral attachment to the ACE2 receptor and entry into the host cells, thus specifying it as a target to prevent the viral infection [20,22]. Though a few recent and related studies have suggested various natural products for the development/repurposing of anti SARS-CoV2 drug targeting Spike glycoprotein, Membrane glycoprotein and Main protease [20,23,24], to the best of our knowledge none has investigated the potentiality of sanguinarine or eugenol for this purpose.…”

Targeting Multiple Signal Transduction Pathways of SARS-CoV-2: Approaches to COVID-19 Therapeutic Candidates

“…Another in silico approach also revealed that curcumin and catechin were used as potential antiviral polyphenols through the dual inhibition of host cell receptors to the virus (mediated by ACE2) and viral protein entry (S-protein). It should be mentioned that the binding affinity of catechin was more than that of curcumin [ 243 ].…”

Entry-inhibitory role of catechins against SARS-CoV-2 and its UK variant

“…Catechins from green tea bind to S1 domain of the spike protein and block its interaction with ACE2 receptor, thus preventing the viral infection. Another study suggests that catechins bind to the amino acids near the receptor binding domain (RBD) of the spike protein and cause fluctuations of alpha helices and beta strands of the RBD-ACE2 complex, thereby hindering the formation of the RBD-ACE2 complex [ 32 ].…”