Inhibition studies of HBV DNA polymerase using seed extracts of Pongamia pinnata

Abstract

Several antiviral compounds for HBV have been identified from traditionally used medicinal plants. We have earlier described the immune modulation properties of P. pinnata, a traditionally used Indian medicinal plant. Therefore, it is of interest to explore the anti-Hepatitis B virus activity of P. pinnata extracts by in-vitro screening assays. This study clearly demonstrated that the 5mg/ml concentration of the aqueous extract significantly inhibited the virus binding. Further, the spectral study was carried out for finding active compounds. The active chalcone derivatives namely, glabaarachalcone, and isopongachromene were isolated from P. pinnata aqueous seed extracts by standard spectral procedures. Virtual screening data shows that glabaarachalcone, and isopongachromene bound with HBV DNA polymerase protein target.

A comprehensive review on the antiviral activities of chalcones

“…These promising diverse antiviral bioactions, make chalcone derivatives a favourable broad-spectrum candidate for targeting the most recent viral pandemic, COVID-19 and any other potentially emerging viral diseases. Their interesting biological activities have been studied in several scientific investigations as potential pharmacological agents capable of targeting a variety of human viruses including; MERS-CoV, severe acute respiratory syndromerelated coronavirus (SARS-CoV), HIV, influenza virus, human rhinovirus, herpes simplex virus (HSV), dengue virus (DEN), human cytomegalovirus (HCMV), hepatitis B virus (HBV), hepatitis C virus (HCV), Rift Valley fever (RVF) and Venezuelan equine encephalitis virus (VEEV), through their well discovered antiviral cellular targets and based on specific chalcone skeleton design [20][21][22][23][24][25][26][27][28][29][30]. Figure 1 illustrates the main mechanisms of actions of chalcone derivatives that were reported in literature on different human viruses.…”

“…Few studies only investigated chalcones role on HBV [28,30]. Patil et al synthesised a group of substituted aryl/heteroaryl derived thienyl chalcones and reported that the more rigid, less bulky thiophenylindenone derivative was the most potent at inhibiting DNA hybridisation in vitro (EC 50 : 4.2 lM; good selectivity index: >24) [30].…”

“…These results demonstrate that chalones can be a potentially good candidates for inhibiting the replication of DNA viruses. In a study by Mathayan et al, they investigated the anti-HBV effects of the P. pinnata seeds, which contains some chalcone derivatives [28]. At a concentration of 5 mg/mL, P. pinnata extract significantly inhibited HBV replication (virus concentration of 0.18 pg/mL; p < .001) with no apparent toxicity [28].…”

“…In a study by Mathayan et al, they investigated the anti-HBV effects of the P. pinnata seeds, which contains some chalcone derivatives [28]. At a concentration of 5 mg/mL, P. pinnata extract significantly inhibited HBV replication (virus concentration of 0.18 pg/mL; p < .001) with no apparent toxicity [28]. On the other hand, molecular docking studies showed that two chalone derivatives (isopongachromene and glabaarachalcone) present in P. pinnata bind to the HBV DNA polymerase protein [28].…”

Natural Products: Review for Their Effects of Anti-HBV

“…In recent years, molecular docking technology was used to screen the active ingredients against HBV, a 3D structure of HBV polymerase (Pol/RT) was modeled and docked with the active compounds, and quercetin ( 18 ) was proved that could enhance its anti-HBV activity up to 10% [ 32 ]. In addition, some researchers found that glabaarachalcone ( 19 ) and isopongachromene ( 20 ), isolated from P. pinnata , could bound with HBV-DNA polymerase protein target [ 33 ]. Isooriention ( 21 ), isolated from S. mussotii , displayed significant anti-HBV activities against the secretions of HBsAg and HBeAg with IC 50 value of 0.79 and 1.12 mM, as well as HBV-DNA replication with IC 50 value of 0.02 mM [ 34 ].…”