The potential SARS-CoV-2 entry inhibitor

Abstract

Outbreak of coronavirus disease 2019 occurred in Wuhan and has rapidly spread to almost all parts of world. In coronaviruses, the receptor binding domain (RBD) in the distal part of S1 subunit of SARS-CoV-2 spike protein can directly bind to angiotensin converting enzyme 2 (ACE2). RBD promote viral entry into the host cells and is an important therapeutic target. In this study, we discovered that theaflavin showed the lower idock score (idock score: −7.95 kcal/mol). To confirm the result, we discovered that theaflavin showed FullFitness score of -991.21 kcal/mol and estimated ΔG of -8.53 kcal/mol for the most favorable interaction with contact area of SARS-CoV-2 RBD by SwissDock service. Regarding contact modes, hydrophobic interactions contribute significantly in binding and additional hydrogen bonds were formed between theaflavin and Arg454, Phe456, Asn460, Cys480, Gln493, Asn501 and Val503 of SARS-CoV-2 RBD, near the direct contact area with ACE2. Our results suggest that theaflavin could be the candidate of SARS-CoV-2 entry inhibitor for further study. 4 Keywords： SARS-CoV-2, spike protein, receptor binding domain, theaflavin

Significant inactivation of SARS-CoV-2 by a green tea catechin, a catechin-derivative and galloylated theaflavinsin vitro

“…6), strongly suggesting that these catechin derivatives may interact with RBD of S protein to prevent viral attachment to ACE2 on the cell surface. Our results are not consistent with previous in silico docking simulation studies that suggested high affinity binding of EGCG and non-galloylated theaflavin to RBD 11,12 .…”

Phenolic compounds disrupt spike-mediated receptor-binding and entry of SARS-CoV-2 pseudo-virions

“…specifically reported on theaflavin-3,3’-digallate as an inhibitor of serine protease NS2B-NS3 of the Zika virus [ 43 ]. Moreover, it was found from in silica study that theaflavins have a high binding affinity (i,e., ΔG of −8.53 kcal/mol) to the RBD of SARS-CoV-2 through forming hydrophobic interactions along with hydrogen bonds at ARG454, PHE456, ASN460, CYS480, GLN493, ASN501, and VAL503 of RBD-SARS-CoV-2, in proximity of the ACE2-spike protein contact area [ 44 ]. Also, Maiti and Banerjee reported that theaflavin gallate prevents the RBD spike protein from binding to the hACE2 receptor [ 45 ].…”

“…It is also a well-known fact that their adequate intake may help to modulate immune responses and resistance to infection. The efficacy of polyphenols as antiviral compounds has been frequently reported, and there is an enormous potential in exploring their antiviral properties, since they are commonly recognized as safe and effective in substituting for, or in serving as an adjunct treatment to, conventional therapies [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50]. Although, there is already substantial information about polyphenols' activity against SARS-CoV-2, most of these results are derived from computational modeling and computational predictions, and their capability as anti-SARS-CoV-2 agents still needs to be scientifically and clinically evaluated.…”

An exhaustive comprehension of the role of herbal medicines in Pre- and Post-COVID manifestations

“…The effective flavonoids found in this study can be ordered as follows affinity hesperidin > rutin > diosmin > apiin > diacetylcurcumin ( Adem et al, 2020 ). Lung et al (2020) in the computational study evaluated the potential of theaflavin. The theaflavin showed a high docking score with good binding with the RBD in SARS-CoV-2.…”

“…The driving forces of these interactions were hydrophobic interactions with hydrogen bonds at sites such as ARG454, ASN460, ASN501, GLN493, PHE456, CYS480, and VAL503 of SARS-CoV-2 RBD, near the ACE2-S protein. For the utmost promising interaction of theaflavin with the RBD in SARS-COV-2, the binding energy was found to be −8.53 kcal/mol ( Lung et al, 2020 ). In a molecular docking study, Shree et al (2020) worked to identify the SARS-COV-2 Mpro (Main protease) inhibitors.…”