Synthesis and in silico studies of novel pyrazole-based anti-MERS-CoV agents
Marwa Elewa, Mahitab Mohamed, Mohamed S. Nafie, Mohamed M. Said, Adel A. El‐Gendy, Yasmine M. Abdel Aziz · Records of Pharmaceutical and Biomedical Sciences/Records of Pharmaceutical & Biomedical Sciences · 2021
Middle East respiratory syndrome coronavirus MERS-CoV represents a big challenge for the healthcare system all over the world. In the present study, five new compounds 4-8 were synthesized and investigated as anti-MERS-CoV agents. The structures of all the new compounds 4-8 were justified by using micro-analytical and spectral data. Biological results showed that all the screened compounds might serve as promising anti-MERS-CoV agents. They showed CC50 ranging from 0.67 mM to 3.22 mM. This range is superior to the standard antiviral agent Favipiravir with CC50 >400 mM. The most active compounds 4 and 6 were further subjected to Plaque Reduction assay. They showed a promising inhibitory pattern. In silico molecular modeling was performed for all the target compounds 4-8 inside the active site of COVID-19 main protease (PDB: 6LU7) to rationalize their antiviral activity. Keywords anti-MERS-CoV, Favipiravir, pyrazole-based analogues, benzylidene carbohydrazide moiety, COVID-19 main protease (PDB: 6LU7), In silico studies