Theaflavin-3’-O-gallate a Black-tea Constituent Blocked SARS CoV-2 RNA dependant RNA Polymerase Active-site with Better Docking Results than Remdesivir

Abstract

Background Replication of SARS-CoV-2 depends on viral RNA-dependent RNA-polymerase (RdRp). Remdesivir, the broad-spectrum RdRp inhibitor acts as nucleoside-analogues (NAs). Remdesivir has initially been repurposed as a promising drug against SARS-CoV-2 infection with some health hazards like liver damage, allergic reaction, low blood-pressure, and breathing-shortness, throat-swelling. In comparison, theaflavin-3’-O-gallate (TFMG), the abundant black tea component has gained importance in controlling viral infection. TFMG is a non-toxic, non-invasive, antioxidant, anticancer and antiviral molecule. Results Here, we analyzed the inhibitory effect of theaflavin-3’-O-gallate on SARS CoV-2 RdRp in comparison with remdesivir by molecular-docking study. TFMG has been shown more potent in terms of lower Atomic-Contact-Energy (ACE) and higher occupancy of surface area; −393.97 Kcal/mol and 771.90 respectively, favoured with lower desolvation-energy; −9.2 Kcal/mol. TFMG forms more rigid electrostatic and H-bond than remdesivir. TFMG showed strong affinity to RNA primer and template and RNA passage-site of RdRp. Conclusions TFMG can block the catalytic residue, NTP entry site, cation binding site, nsp7-nsp12 junction with binding energy of −6. 72 Kcal/mol with Ki value of 11.79, and interface domain with binding energy of −7.72 and −6.16 Kcal/mol with Ki value of 2.21 and 30.71 µM. And most importantly, TFMG shows antioxidant/anti-inflammatory/antiviral effect on human studies.

The medicinal value of tea drinking in the management of COVID-19

“…Based on molecular docking technology, it has been proved that tea polyphenols, especially theaflavins (TF, TF2B), might inhibit the activities of NSP16 (coronavirus 2′-Omethyltransferase), Angiotensin-converting enzyme 2 (ACE2), RNA replicase (RdRp) and 3C-likeprotease (3CLpro) of SARS-CoV-2, and inhibit the replication and transcription of the virus, thereby preventing the spike protein from attaching to human cells [ [60] , [61] , [62] , [63] ]. In vitro verification confirmed that EGCG in tea could interfere with the binding of SARS-CoV-2 RBD to ACE2 of host cells, or by inhibiting the activity of 3CLpro, thereby blocking the initial invasion process of the virus [ 64 – 66 ].…”

Tea as a natural gift for discovering antiviral candidates

“…Bioinformatics and molecular docking studies by Maiti and Banerjee demonstrated that the TF gallate exhibits greater binding affinity to the SARS-CoV-2 S protein than does hydroxychloroquine (HCQ), thus indicating its superior inhibitory activity compared to that of HCQ [107] . Theaflavin-3’- O -gallate (TFMG) is an enriched compound in black tea that has been demonstrated to block the active portion of SARS-CoV-2 RdRp with better docking than that of remdesivir [68] . Additionally, a virtual screening and molecular dynamics simulation study revealed that TF3 and TF2a exhibit the highest binding affinities towards RdRp, M pro , and PL pro targets on SARS-CoV-2 [5] .…”

“…Interference with SARS-CoV-2 invasion by inhibiting TMPRSS2 [66] OFA M pro Interference with SARS-CoV-2 replication by inhibition of M pro [6] TFs M pro /PL pro /RdRp Interference with M pro , PL pro , and RdRp to block SARS-CoV-2 replication [5,[67][68] WTSNF NF-κB pathway Reduction in the levels of IL-6, IL-1β, IL-17, IL-8, TNF-α, and IFN-γ [69] EGCG: (-)-epigallocatechin-3-gallate; GCG: (-)-gallocatechin gallate; LLPS: Liquid-liquid phase separation; OFA: Oolonghomobisflavan A; TA: Tannic acid; TFs: theaflavins; WTSNF: white-tip silver needle flavonoids.…”

Differences in the secondary metabolites of different varieties of black tea and evaluation of their disease-resistance activity

“…anticancer [11,12], and antitumour [13] activities and can protect against liver and kidney damage [14,15] and enhance immunity [16]. In addition, polyphenols in black tea have been reported to have antioxidant, anticancer, lipid homeostasis [17,18], antidiabetic [19], intestinal ora promotion, and obesity suppression [20] health effects.…”