Plant-derived antiviral drugs as novel hepatitis B virus inhibitors: Cell culture and molecular docking study

Abstract

a b s t r a c tDespite high anti-HBV efficacies, while the nucleoside analogs (e.g., lamivudine) lead to the emergence of drug-resistance, interferons (e.g., IFN-a causes adverse side-effects. Comparatively, various natural or plant products have shown similar or even better efficacy. Hence, new antiviral strategies must focus not only on synthetic molecules but also on potential natural compounds. In this report, we have combined the in vitro cell culture and in silico molecular docking methods to assess the novel anti-HBV activity and delineate the inhibitory mechanism of selected plant-derived pure compounds of different classes. Of the tested (2.5-50 lg/ml) twelve non-cytotoxic compounds, ten (10 lg/ml) were found to maximally inhibit HBsAg production at day 5. Compared to quercetin (73%), baccatin III (71%), psoralen (67%), embelin (65%), menisdaurin (64%) and azadirachtin (62%) that showed high inhibition of HBeAg synthesis, lupeol (52%), rutin (47%), b-sitosterol (43%) and hesperidin (41%) had moderate efficacies against HBV replication. Further assessment of quercetin in combination with the highly active compounds, enhanced its anti-HBV activity up to 10%. Being the most important drug target, a 3-D structure of HBV polymerase (Pol/RT) was modeled and docked with the active compounds, including lamivudine as standard. Docking of lamivudine indicated strong interaction with the modeled HBV Pol active-site residues that formed stable complex (ΔG = À5.2 kcal/mol). Similarly, all the docked antiviral compounds formed very stable complexes with HBV Pol (ΔG = À6.1 to À9.3 kcal/mol). Taken together, our data suggest the anti-HBV potential of the tested natural compounds as novel viral Pol/RT inhibitors. Ó 2018 The Authors. Production and hosting by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

An investigation into the identification of potential inhibitors of SARS-CoV-2 main protease using molecular docking study

“…Rutin, also known as vitamin P, has several pharmacological properties including anti-viral activity (Ganeshpurkar & Saluja, 2017). Similarly, hesperidin has also been observed to act as an anti-viral compound (Parvez et al, 2019). Therefore, this finding also indicates a promising potential for the use of dietary polyphenols for the treatment of COVID-19.…”

Recognition of Natural Products as Potential Inhibitors of COVID-19 Main Protease (Mpro): In-Silico Evidences

“…These natural products may act as a promising candidate to combat the COVID-19. Another potential natural product found in S. cusia leaf is β-sitosterol, a phytosterol which is recognized for its in vitro enzymatic inhibitory activity against SARS coronavirus 3C-like protease [36] and anti-HBV (hepatitis B virus) activity [37]. Besides this, it also exhibits antibacterial, anti-inflammatory and antitumor activities [38][39][40].…”

The anti‐hepatitis B virus therapeutic potential of anthraquinones derived from Aloe vera

“…In the absence of a crystal structure, a recently modelled HBVpol protein (Parvez et al, ) was used for molecular docking of the AV‐derived antiviral anthraquinones. The binding mechanism of aloin B, aloe‐emodin, and chrysophanol with HBVpol was evaluated using Autodock 4.2 as described previously (Al‐Yousef, Ahmed, Al‐Shabib, et al, ; Morris et al, ).…”

“…Notably, despite high efficacies, most of the HBVpol inhibitors, such as lamivudine, adepovir, entecavir, and so forth lead to the emergence of drug‐resistance and failure to chemotherapy (Teo & Locarnini, ). In the recent decade, traditional and indigenous herbal medicines or plant metabolites have gained much attention for their remarkable anti‐HBV effects (Arbab, Parvez, Al‐Dosari, et al, ; Arbab, Parvez, Al‐Dosari, & Al‐Rehaily, ; Chen & Zhu, ; Parvez et al, ; Parvez, Arab, Al‐Dosari, & Al‐Rehaily, ; Qi et al, ; Wang, Zhang, & Bonkovsky, ; Wu, ; Yang et al, ; Zhang et al, ).…”