Catechin and curcumin interact with S protein of SARS-CoV2 and ACE2 of human cell membrane: insights from computational studies
Authors: Jagneshwar Dandapat
G B N Chainy
Atala B Jena
Namrata Kanungo
Vinayak Nayak
Journal: Scientific Reports (2021)
Discipline: Multidisciplinary
Keywords: coronavirus; SARS-CoV2; spike protein; ACE2; interventions
Affiliations: Centre of Excellence in Integrated Omics and Computational Biology, Utkal University, Bhubaneswar, 751004, Odisha, India., Post Graduate Department of Biotechnology, Utkal University, Bhubaneswar, 751004, Odisha, India., Centre of Excellence in Integrated Omics and Computational Biology, Utkal University, Bhubaneswar, 751004, Odisha, India. .

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. 

Retracted: No

PubPeer comments:
 1. In methodology, the author used clusPro2.0 to perform protein-protein interaction between S protein and ACE2 in the presence and absence of catechin and curcumin. However, a protein coordinated with a ligand molecule cannot be uploaded. Water molecules, hetero atoms, and such will be deleted automatically during structure preparation on the website. As a result, docking such a protein-protein interaction with the presence of any ligands is impossible. u2028 2. It was not justified how the author defined the binding sites of S protein, ACE2, and RBD ACE2 for Catenine and Curcumin. u2028 3. The optimal protein-protein complex posture in clusPro2.0 was determined by the maximum number of cluster arrivals and a weighted scoring function. However, the author used this weighted scoring as a binding energy, in terms of binding affinity, which is incorrect. Following the scoring, they also added the kj mol unit. It is unknown how and where the author discovered that the scoring unit is kj mol. Thus, the methodology and data presented in this work are non-reproducible and misleading. ,