Evaluation of novel pyrrolopyrimidine derivatives as antiviral against gastroenteric viral infections

Abstract

Viral gastroenteritis is a major global public-health threat. All age groups are susceptible for this infection, but its most serious consequences affect children. Rotavirus, Coxsackievirus and Adenovirus are the most common viruses that cause gastroenteritis. Herein, we synthesized novel pyrrole, pyrrolo[2,3‑d]pyrimidine and pyrrolo[3,2‑e][1,2,4]triazolo[4,3‑c]pyrimidine derivatives. The non-toxic doses of these compounds were determined using BGM cell lines. We examined all the new compounds for their anti-viral activities against Rotavirus Wa strain and Coxsackievirus B4. Compounds 2a, 2d, 5a, 5c, 5d, 7b, 7j, 7n, 14b, 14c, 14e and 14f exhibited significant antiviral activity. We interpreted the action of these compounds using molecular docking against the homology models of viral polymerase enzymes of these viruses. RMSD value of 5d/Coxsackievirus was higher than the RMSD value for 5d/rotavirus and hence better as a stability parameter, which can be correlated to the biological activity.

Keywords: Antiviral drugs; Coxsackievirus B4; Homology modelling, molecular dynamics; Molecular modelling; Pyrrole; Pyrrolo[2,3‑d]pyrimidine; Pyrrolo[3,2‑e][1,2,4]triazolo[4,3‑c]pyrimidine; Rotavirus; Viral gastroenteritis.