Molecular Dynamic Study and Synthesis of 1H-benzo[d]imidazole-5-carboxamide Derivatives as Inhibitors for Yellow Fever and Zika Virus Replication
Mitry, M., El-Araby, A., Neyts, J., Kaptein, S., Serya, R., Samir, N. (2020). Molecular Dynamic Study and Synthesis of 1H-benzo[d]imidazole-5-carboxamide Derivatives as Inhibitors for Yellow Fever and Zika Virus Replication. EKB Journal Management System, 4(2), 145-180. doi: 10.21608/aps.2020.34690.1036
Madonna M. A. Mitry; Amr El-Araby; johan Neyts; Suzanne Kaptein; Rabah A. T. Serya; Nermin Samir. "Molecular Dynamic Study and Synthesis of 1H-benzo[d]imidazole-5-carboxamide Derivatives as Inhibitors for Yellow Fever and Zika Virus Replication". EKB Journal Management System, 4, 2, 2020, 145-180. doi: 10.21608/aps.2020.34690.1036
Mitry, M., El-Araby, A., Neyts, J., Kaptein, S., Serya, R., Samir, N. (2020). 'Molecular Dynamic Study and Synthesis of 1H-benzo[d]imidazole-5-carboxamide Derivatives as Inhibitors for Yellow Fever and Zika Virus Replication', EKB Journal Management System, 4(2), pp. 145-180. doi: 10.21608/aps.2020.34690.1036
Mitry, M., El-Araby, A., Neyts, J., Kaptein, S., Serya, R., Samir, N. Molecular Dynamic Study and Synthesis of 1H-benzo[d]imidazole-5-carboxamide Derivatives as Inhibitors for Yellow Fever and Zika Virus Replication. EKB Journal Management System, 2020; 4(2): 145-180. doi: 10.21608/aps.2020.34690.1036

Molecular Dynamic Study and Synthesis of 1H-benzo[d]imidazole-5-carboxamide Derivatives as Inhibitors for Yellow Fever and Zika Virus Replication

Archives of Pharmaceutical Sciences Ain Shams University
Article 1, Volume 4, Issue 2, December 2020, Page 145-180  XML PDF (1.35 MB)
Document Type: Original Article
DOI: 10.21608/aps.2020.34690.1036
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Authors
Madonna M. A. Mitry1; Amr El-Araby2; johan Neyts3; Suzanne Kaptein3; Rabah A. T. Serya1; Nermin Samir email orcid 2
1Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt
2Department of pharmaceutical chemistry, Faculty of pharmacy, Ain Shams university
3Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Herestraat 49, 3000 Leuven, Belgium.
Abstract
Flaviviridae family comprises the flavivirus genotype that represents a significant world health problem as it includes the Yellow fever virus (YFV) and Zika virus (ZIKV) which are responsible for large outbreaks and for which novel therapies are in urgent demand. The benzimidazole scaffold has been widely reported for its antiviral activity, and hence a new series of 1H-benzo[d]imidazole-5-carboxamide derivatives (VIIa-x, VIIIa-h & IXa, b) was designed, synthesized, and biologically evaluated for their antiviral activity. 5 Compounds (VIId, VIIe, VIIh, VIIn and VIIt) showed antiviral activity against YFV in the low micromolar range using the human hepatoma Huh-7 cells and Vero cells. One compound (VIId) exhibited activity on both YFV (EC50=1.7 ± 0.8µM) and ZIKV (EC50=4.5 ± 2.1µM). Molecular docking and molecular dynamics simulation studies were conducted to understand the SAR of newly synthesized compounds, to explore the potential target of compound VIId and to investigate the possible binding mode to its target.
Keywords
1H-benzo[d]imidazole; Flavivirus; Yellow Fever virus; Zika virus; Molecular dynamics simulation
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