In Silico Studies of Medicinal Compounds against Hepatitis C Capsid Protein from North India

Abstract

Hepatitis viral infection is a leading cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Over one million people are estimated to be persistently infected with hepatitis C virus (HCV) worldwide. As capsid core protein is the key element in spreading HCV; hence, it is considered to be the superlative target of antiviral compounds. Novel drug inhibitors of HCV are in need to complement or replace the current treatments such as pegylated interferon’s and ribavirin as they are partially booming and beset with various side effects. Our study was conducted to predict 3D structure of capsid core protein of HCV from northern part of India. Core, the capsid protein of HCV, handles the assembly and packaging of HCV RNA genome and is the least variable of all the ten HCV proteins among the six HCV genotypes. Therefore, we screened four phytochemicals inhibitors that are known to disrupt the interactions of core and other HCV proteins such as (a) epigallocatechin gallate (EGCG), (b) ladanein, (c) naringenin, and (d) silybin extracted from medicinal plants; targeted against active site of residues of HCV-genotype 3 (G3) (Q68867) and its subtypes 3b (Q68861) and 3g (Q68865) from north India. To study the inhibitory activity of the recruited flavonoids, we conducted a quantitative structure–activity relationship (QSAR). Furthermore, docking interaction suggests that EGCG showed a maximum number of hydrogen bond (H-bond) interactions with all the three modeled capsid proteins with high interaction energy followed by naringenin and silybin. Thus, our results strongly correlate the inhibitory activity of the selected bioflavonoid. Finally, the dynamic predicted capsid protein molecule of HCV virion provides a general avenue to target structure-based antiviral compounds that support the hypothesis that the screened inhibitors for viral capsid might constitute new class of potent agents but further confirmation is necessary using in vitro and in vivo studies.

Beneficial effects of naringenin in liver diseases: Molecular mechanisms

“…On the other hand, in silico studies have been carried out to evaluate naringenin activity on the HCV particle. Mathew et al[ 208 ] in 2014 reported a docking interaction study between the 3D structure of capsid core protein of HCV-genotype 3 (G3) (Q68867) and its subtypes 3b (Q68861) and 3g (Q68865) from north India and naringenin. The results indicated that the flavonoid exhibited five, seven and nine H-bond interactions within the core protein of HCV-G3, subtypes 3b and 3g, respectively.…”

“…In the case of HCV-3b, naringenin formed three H-bonds with TRP90, two with GLN86, and one with GLY84 and TRP93, with an interaction energy of -145.682 kcal/mole. Finally, the flavanone binds to HCV-3g through two H-bonds with TRP73 and GLY77 and individually with ASN85, TYR78 and TRP73 with an interaction energy of -159.483 kcal/mole[ 208 ]. These results suggest that naringenin binds to the core protein of three important HCV genotypes in India, especially to HCV-3 based on their interaction energies; this ability of naringenin to bind core protein could be involved in the inhibition of viral particle assembly that was previously reported.…”

Updates on Traditional Medicinal Plants for Hepatocellular Carcinoma

“…In these patients, local ablative therapies, including chemoembolization, potentially novel chemotherapeutic agents and radiofrequency ablation (RFA), may provide palliation and extend life. With the emergence of extremely effective direct-acting antivirals (DAAs) for hepatitis, 1 it is expected to reduce the incidence of hepatitis-related HCC. 3 Overall, a combination of virus-specific, environmental, immune-related factors and host genetics are likely to determine the progression and treatment of HCC.…”

“…69 The antiviral activity of ladanein has been demonstrated effective against all HCV genotypes which lead to liver cancer. 1,70…”

“…Cancers that arise in any other part of the body, such as lung, colon or breast and spread to the liver is called as metastatic cancer rather than liver cancer. 1 People acquire liver cancer in the context of chronic liver disease (cirrhosis), which increases the risk of liver cancer with scars. Conditions that cause liver cirrhosis are chronic hepatitis B, hepatitis C, alcohol usage, genetic predisposition, iron and copper overloads, and drug abuse ( Figure 1).…”