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

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.

Automated summary

Globally, rotavirus is the leading cause of acute gastroenteritis in infants and toddlers, but there are currently no specific treatments for rotavirus infection. Immunization programs are being implemented worldwide to reduce the impact of rotavirus, but there are no approved antiviral drugs that can attack rotavirus in hosts. Benzoquinazoline derivatives synthesized in the laboratory showed good antiviral activity against various viruses. In this research, the effectiveness of benzoquinazoline derivatives against human rotavirus Wa strains was investigated in vitro. Compounds 1-3, 9, and 16 showed the highest activity, potentially inhibiting the outer capsid protein VP4.