Evaluation of Some Benzo[g]Quinazoline Derivatives as Antiviral Agents against Human Rotavirus Wa Strain: Biological Screening and Docking Study

Abstract

Globally, rotavirus (RV) is the most common cause of acute gastroenteritis in infants and toddlers; however, there are currently no agents available that are tailored to treat rotavirus infection in particular. Improved and widespread immunization programs are being implemented worldwide to reduce rotavirus morbidity and mortality. Despite certain immunizations, there are no licensed antivirals that can attack rotavirus in hosts. Benzoquinazolines, chemical components synthesized in our laboratory, were developed as antiviral agents, and showed good activity against herpes simplex, coxsackievirus B4 and hepatitis A and C. In this research project, an in vitro investigation of the effectiveness of benzoquinazoline derivatives 1–16 against human rotavirus Wa strains was carried out. All compounds exhibited antiviral activity, however compounds 1–3, 9 and 16 showed the greatest activity (reduction percentages ranged from 50 to 66%). In-silico molecular docking of highly active compounds, which were selected after studying the biological activity of all investigated of benzo[g]quinazolines compounds, was implemented into the protein’s putative binding site to establish an optimal orientation for binding. As a result, compounds 1, 3, 9, and 16 are promising anti-rotavirus Wa strains that lead with Outer Capsid protein VP4 inhibition.

Synthesis of novel spirochromane incorporating Schiff's bases, potential antiproliferative activity, and dual EGFR/HER2 inhibition: Cell cycle analysis and in silico study

“…In addition, it is used to explore the interactionsof ligands within the receptor- or putative enzyme-binding sites ( Al-Suwaidan et al, 2015 , Alanazi et al, 2016 ). The selected compounds and co-crystallized inhibitors were subjected to molecular docking at the protein-binding sites to ensure docking accuracy and validation ( Hamdi et al, 2022a , Hamdi et al, 2022b , Abuelizz et al, 2023 ).…”

Promising Schiff bases in antiviral drug design and discovery

“…Quinoline and quinazoline are heterocyclic moieties with well-reported antiviral properties. During investigation of a potential drug to control the pandemic caused by SARS-CoV2, it has been found that RNA-dependent RNA polymerase (RdRp) has a pivotal viral life cycle and quinoline and quinazoline derivatives not only inhibit RNA virus-like HIV-1, Ebola virus, Influenza virus but also shows activity against DNA viruses such as HSV (Herpes simplex virus) and Hepatitis B virus [ 78 – 82 ]. In continuation of exploring this moiety, Zhao et al synthesized 101 quinoline and quinazoline derivatives and on screening using a cell-based assay, it was found that the inhibition activity shown by the compounds are 5e = 95.03%, 5h = 92.85%, and 5i = 74.94%.…”