Prediction of HBF-0259 interactions with hepatitis B Virus receptors and surface antigen secretory factors

Abstract

Hepatitis B virus (HBV) is an etiological agent of viral hepatitis, which may lead to cirrhosis, and hepatocellular carcinoma. Current treatment strategies have not shown promising effect to date but various complications such as, drug toxicity-resistance have been reported. Study on newly discovered compounds, with minimal side effects, as specific HBV inhibitors is a fundamental subject introducing new biologic drugs. Here, we aimed to, by prediction, estimate interactions of HBF-0259 as a nontoxic anti-HBV compound on inhibiting the HBV through either interaction with the viral entry or HBsAg secreting factors using In Silico procedure. Molecular docking was performed by Hex 8.0.0 software to predict the interaction energy (Etot) between HBF-0259 and known cellular factors involved in HBV entry and HBsAg secreting factors. Hex 8.0.0 also employed to create protein-protein complexes. These interactions were then used to analyze the binding site of HBF-0259 within the assumed receptors by MGLTools software. Finally, the amino acid sequences involved in this interaction were aligned for any conservancy. Here, we showed that HBF-0259 Etot with CypA (-545.41 kcal/mol) and SCCA1 (499.68 kcal/mol), involved in HBsAg secretion and HBV integration, respectively, was higher than other interactions. Furthermore, HBF-0259 predicted interaction energy was even higher than those of CypA inhibitors. In addition, we claim that preS1 and/or preS2 regions within HBsAg are not suitable targets for HBF-0259. HBF-0259 has higher interaction energy with CypA and SCCA1, even more than other known receptors, co-receptors, viral ligands, and secretory factors. HBF-0259 could be introduced as potent anti-viral compound in which CypA and or SCCA1, as previously shown, are involved.

Susceptibility of the Iranian Population to Severe Acute Respiratory Syndrome Coronavirus 2 Infection Based On Variants of Angiotensin I Converting Enzyme 2

“…The results of docking SARS-CoV-2 glycoprotein with the ACE2 variants were analyzed by MGLTools 1.5.6 software (The Scripps Research Institute, CA, USA) for determining ACE2 amino acids residues involved in interaction with the viral glycoprotein. The interaction analysis were done according to visual molecular dynamics (VDW) scaling factor 1 Å and the amino acid position(s) of all binding sites were investigated and validated in UniProt database regarding the molecular domains [ 26 ].…”

Novel homozygous HEXB mutation identified in a consanguineous Iranian pedigree with Sandhoff disease

“…The structures of Beta-hexosaminidase subunit beta was carried out using molecular modeling tools server [21].the sequences and 3D shapes of hex b as well as ligand were acquired from protein databank (PDB) [22].The crystallographic structure of molecules was removed for the existence of water atoms and other unnecessary additional chains using UCSF Chimera 1.8.1 [23] [24]. Protein homology modeling of the newly-identified mutated HEXB protein, p.A278V, was carried out using the online Swiss-Prot server for automated modeling [25].protein structure prediction server, RaptorX, was also used for homology based 3D structure prediction [26].…”

An Overview of Hepatitis B Virus Surface Antigen Secretion Inhibitors

“…In a time- and dose-dependent manner, HBF-0259 specifically targets all forms of HBsAg in HBsAg expressing cells, HepH2.2.15 and HepDE19 ( Dougherty et al, 2007 ). This mechanism of action may be underlain beneath of its interaction with cellular secretory or HBsAg post-translationally modifying factors ( Dougherty et al, 2007 ; Mohebbi et al, 2016 ). Long-term treatment assay of HBF-0259 has been shown no traceable level of glycosylated forms of HBsAg in the supernatant ( Dougherty et al, 2007 ).…”

“…Meanwhile, only intracellular non-glycosylated forms of HBsAg have been observed. This indicates that HBF-0259 may target cellular counterparts involved in HBsAg modification and secretion ( Mohebbi et al, 2016 ). Moreover, HBF-0259 had no significant effect on HBV DNA replication.…”