Epigallocatechin-Gallate and Theaflavin-Gallate Interaction in SARS CoV-2 Spike-Protein Central-Channel with Reference to the Hydroxychloroquine Interaction: Bioinformatics and Molecular Docking Study

Abstract

SARS CoV-2 or COVID-19 pandemic global-outbreak created the most unstable situation of human health-economy. Last two decades different parts of the word experienced smaller or bigger outbreak related to human-coronaviruses. The spikeglycoproteins of the COVID-19 (similar to SARS-CoV) attach to the angiotensin-converting-enzyme (ACE-2) and transit over a stabilized open-state for the viral-internalization to the host-cells and propagate with great efficacy. Higher rate of mutability makes this virus unpredictable/less-sensitive to the protein/nucleic-acid based-drugs. In this emergent situation, drug-induced destabilization of spike-binding to RBD could be a good strategy. In the current study we demonstrated by Bioinformatics (CASTp: Computed-Atlas-of-Surface-Topography, PyMol: molecular-visualization) and Molecular docking (PatchDock) experiments that tea flavonoids catechin-products mainly EGCG or other like theaflavin gallate demonstrated higher Atomic Contact Energy (ACE), surface area and more amino-acid interactions than hydroxychloroquine (HCQ) during binding in the central channel of the spike-protein. Moreover, out of three distinct binding-sites (I, II and III) of spike core when HCQ binds only with site III (farthest from the nCoV-RBD of ACE2 contact), EGCG and TG bind all three sites. As because site I and II is in closer contact with open state location and viral-host contact area so these drugs might have significant effects. Taking into account the toxicity/side-effects by CQ/HCQ, present drugs may be important. Our laboratory is working on tea flavonoids and other phytochemicals in the protection from toxicity, DNA/mitochondrial damage, inflammation etc. The present data might be helpful for further analysis of flavonoids in this emergent pandemic situation.

Active-site Molecular docking of Nigellidine to nucleocapsid/Nsp2/Nsp3/MPro of COVID-19 and to human IL1R and TNFR1/2 may stop viral-growth/cytokine-flood, and the drug source Nigella sativa (black cumin) seeds show potent antioxidant role in experimental rats.

“…This has been demonstrated in our previous findings on some suitable epitope-screening from SARS CoV 2 spike[23]. Our earlier study also demonstrated that Epigallocatechin gallate (EGCG) and Theaflavin gallate (TDG) are the potent binder to the CoV 2 spike channel[24]. Increased cytokines and other hematopoetic parameters (oxidative stress markers) by LPS-administration have been shown to terminate by Nigella sativa (NS) extract[25].Cardio-respiratory and endothelial dysfunction is one of the major symptoms of SARS CoV 2 infection.And this dysfunction may be counteracted by NS and its component thymoquinone by restraining interleukin-1β, TNF-α and NF-κB signaling[26].…”

In silico analysis of the interactions of certain flavonoids with the receptor-binding domain of 2019 novel coronavirus and cellular proteases and their pharmacokinetic properties

“…Some recent studies have shown that catechins can be used as alternative agents in COVID-19 infection. According to Maiti and Banerjee ( 2020 ), catechins, such as epigallocatechin gallate or theaflavin gallate, interact more strongly with the amino acids of the spike protein than hydroxychloroquine. There are also some data in the literature that some catechins, such as theaflavin digallate, epigallocatechin gallate and gallocatechin gallate, inhibit the main protease of 2019-nCoV together with the spike glycoprotein (Manish, 2020 ; Peterson, 2020 ; Sayed et al., 2020 ; Tallei et al., 2020 ).…”

Therapeutic and prophylactic effect of flavonoids inpost‐COVID‐19 therapy

“…Thus, SARS‐CoV‐2 cannot fuse with ACE2 (Abderrazak et al, 2015; Muchtaridi et al, 2020; J. W. Yu et al, 2020; Zhai et al, 2020). Baicalin, scutellarin, hesperetin, nicotianamine, glycyrrhizin (H. Chen & Du, 2020), epigallocatechin‐3‐gallate, theaflavin gallate (Maiti & Banerjee, 2021), naringenin, quercetin, luteolin (Maurya, Kumar, Prasad, Bhatt, & Saxena, 2020), fisetin, kaempferol (Pandey et al, 2020) were due to anti‐SARS‐CoV‐2 effect and to the low toxicity selected as potential candidates for COVID‐19 treatment.…”