Human adenovirus DNA polymerase is evolutionarily and functionally associated with human telomerase reverse transcriptase based on in silico molecular characterization that implicate abacavir and zidovudine

Abstract

Human adenoviruses (HAdVs) are non-enveloped, small double stranded DNA (dsDNA) viruses that cause asymptomatic infections, clinical syndromes and significant susceptibility to infections in immunocompromised people. The aim of the present study was to identify critical host proteins and HAdV hypothetical proteins that could be developed as potential host-viral targets for antiHAdV therapy. Here, the function of selected hypothetical proteins of HAdV based on phylogenetic relationship with the therapeutic targets of antiretroviral drugs of human immunodeficiency virus (HIV) was predicted computationally, and characterized the molecular dynamics and binding affinity of DNA polymerase of HAdV. Thirty-eight hypothetical proteins (HPs) of human adenovirus (HAdV) were used in this study. The results showed that HAdV DNA polymerase (P03261) is related to Human TERT (O14746) and HLA-B (P01889) genes. The protein-protein interaction of human five molecular targets (PNP, TERT, CCR5, HLA-B, and NR1I2) of ARVDs are well-coordinated/networked with CD4, AHR, FKBP4, NR3C1, HSP90AA1, and STUB1 proteins in the anti-HIV infection mechanism. The results showed that the free energy score of abacavir and zidovudine binding to HAdV DNA polymerase are −5.8 and −5.4 kcal mol-1 respectively. Also, the control drug, cidofovir and ganciclovir have less binding affinity for DNA polymerase of HAdV when compare to that of abacavir and zidovudine. Similarity was observed in the binding of abacavir and zidovudine to HAdV DNA polymerase (ASP742, ALA743, LEU772, ARG773 and VAL776). In conclusion, combination of abacavir and zidovudine was predicted to be potential therapy for controlling HAdV infection targeting HAdV DNA polymerase.

In silico ADME and molecular simulation studies of pharmacological activities of phytoconstituents of Annona muricata (L.) Fruit

“…The protein-ligand interactions stacked bar charts are normalized over the course of the trajectory; for instance, a value of 0.7 suggests that 70% of the simulation time the specific interaction was maintained. Prime MM-GBSA provides various energy properties, reporting energies for ligand, receptor, and complex structures, along with energy differences related to strain and binding (Fatoki, 2023). The total binding free energy confirms the stability of the complexes under physiological conditions.…”

“…Molecular dynamics simulation (MDS) was employed to assess atomic-level variations in the protein-ligand system and evaluate the stability of the protein-ligand complex in a dynamic environment (Fatoki, 2023). MD simulations track the evolution of cartesian coordinates for every atom in a system using a general physics model governing particle interaction (McCammon and Karplus, 2002).…”

In silico exploration of anti-prostate cancer compounds from differential expressed genes

“…The molecular docking studies were conducted following the methodology described by Fatoki et al [ 26 ]. Initially, the three-dimensional structures of the most probable proteins were obtained as AlphaFold pdb format through the UniProt database (UniProt IDs: Q12809; P35462; P35228; P00533, P06241; P23415; and P11388).…”

“…MD simulations were conducted using Desmond v3.6, in a Schrödinger LLC software v2021-1 [ 26 , 31 , 32 ]. Desmond is a high-performance molecular dynamics (MD) simulation software developed by D. E. Shaw Research.…”

“…The post-simulation analyses of the trajectories were done to determine the root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), and protein-ligand interaction profile. Also, prime molecular mechanics/generalized Born surface area (MMGBSA) was used to evaluate the binding free energy [ 26 , 35 , 36 ], as follows:…”