Theaflavins, polyphenols of black tea, inhibit entry of hepatitis C virus

Abstract

20The treatment of hepatitis C virus (HCV) infection by combination of direct acting antivirals 21 (DAA), with different mode of action, has made substantial progress in the past few years. 22 3 47 development of HCV direct acting antivirals (DAA) like Daclatasvir, Sofosbuvir and Simeprevir, 48targeting viral proteins NS5A, NS5B polymerase or NS3/4A protease, respectively (5). These 49 approved DAA prominently increase the sustained viral response (SVR) up to ~95% in most 50 patients, depending primarily on disease stage and the genotype of the infecting virus (5). 51However, treatment with DAAs is not without limitation; it is associated with side-effects, 52 resurgence of infection in transplant patient and high cost especially in developing countries 53 (6,7). Approved DAAs mainly target the virus replication leading to emergence of resistance 54 mutations in this RNA virus genome (8). Thus, novel combinations of low cost entry inhibitors 55 with conventional treatment targeting different stages of the HCV life cycle, may provide a 56 promising approach against HCV drug resistance development and infection relapse (9). 57 Moreover, prevention of donor liver re-infection by inhibiting viral entry into hepatocytes might 58 be achieved using DAAs targeting entry. 59 Hepatitis C virus is an enveloped positive-stranded RNA virus encoding a polyprotein, co-and 60 post-translationnally cleaved into structural and non-structural proteins (10). Two viral 61 glycoproteins E1 and E2 are part of the lipoviroparticle envelope. Non-structural proteins, NS2 62 to NS5B, are involved in replication and assembly of new virions. Actual antiviral therapy with 63 DAA targets three non-structural proteins, the RNA-dependent RNA polymerase NS5B, a non-64 enzymatic protein involved in replication and assembly of HCV NS5A, and the viral protease 65 NS3/4A, involved in polyprotein processing and essential for viral replication (11). Virus entry 66into hepatocytes is a multistep process that involves attachment of the particle to 67 glycosaminoglycans and subsequent binding to entry factors, SR-B1, CD81, Claudin-1 and 68 Occludin (12). After clathrin-mediated endocytosis and fusion of the viral envelope to 69 endosomal membrane, the viral RNA is replicated, assembled and released via the secretory 70 pathway.

Molecular docking, validation, dynamics simulations, and pharmacokinetic prediction of natural compounds against the SARS-CoV-2 main-protease

“…reported the antiviral property of polyphenolic compounds from black tea namely theaflavin, theaflavin-3′-monogallate, and theaflavin-3-3′-digallate during the early onset of hepatitis C viral infections under in-vitro conditions. Their study reported that theaflavin and its derivatives could inhibit viral replication and cell-to-cell proliferation (Chowdhury et al., 2018 ). They reported an EC 50 value of 17.89, 4.08, and 2.02 μM respectively had a significant impact against viral replication (Chowdhury et al., 2018 ).…”

“…Their study reported that theaflavin and its derivatives could inhibit viral replication and cell-to-cell proliferation (Chowdhury et al., 2018 ). They reported an EC 50 value of 17.89, 4.08, and 2.02 μM respectively had a significant impact against viral replication (Chowdhury et al., 2018 ). Chen et al.…”

Antiviral Phytocompounds: A Methodical Review of Therapeutic Efficiency Against SARS-Like Human Coronaviruses

“…These compounds are well-known for their antioxidant, anti-inflammatory, and other disease-curing abilities [79]. Previously, theaflavins and its derivatives were reported for their effectiveness against Influenza [80], HSV-1 [81], hepatitis C virus [82], calicivirus [83] and HIV-1 [84]. Besides preventing inflammatory cytokine expression, theaflavins are effective in thwarting viral attachment/entry and replication [82,84].…”

“…Previously, theaflavins and its derivatives were reported for their effectiveness against Influenza [80], HSV-1 [81], hepatitis C virus [82], calicivirus [83] and HIV-1 [84]. Besides preventing inflammatory cytokine expression, theaflavins are effective in thwarting viral attachment/entry and replication [82,84]. During the SARS outbreak in 2004, two theaflavin derivatives namely 3-isotheaflavin-3-gallate, theaflavin-3, 3′-digallate alongside tannic acid have been reportedas potential 3 CL Pro inhibitors with IC 50 values 7, 9.5 and 3 µM respectively [85].…”