Amaku James Friday - Academia.edu (original) (raw)
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Bangalore University, M.S.Ramaiah College of Arts ,Science and Commerce
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Papers by Amaku James Friday
Communication in Physical Sciences 2020, 5(3): 391-402, 2020
The devastating impact of viral haemorrhagic fevers has deeply been felt in South America and Afr... more The devastating impact of viral haemorrhagic fevers has deeply been felt in South America and Africa. This fever is caused by the arenaviruses Lassa and has posed a matchless fight. Meanwhile, no effective drug or vaccine has been reported. Here we used virtual screening and molecular docking approach to identify a series of novel inhibitors (ZINC64450313 (-10.7 kcal/mol), ZINC00658482 (-10.5 kcal/mol), ZINC40789449 (-10.5 kcal/mol), ZINC14551223 (10.0 kcal/mol) and ZINC73892903 (10.0 kcal/mol)) that can exhibit significant binding affinity to Lassa fever nucleoprotein (PDB ID: 3mx5) than ribavirin (-6.7 kcal/mol). Swiss ADME web tools were used to assess the pharmacokinetics and drug-likeness characteristics of the lead molecule (ZINC64450313). This assay showed that ZINC64450313 obeyed Lipinski, Egan, Verber and Muegge rules. However, pharmacokinetics predictions indicated that CYP1A2, CYP2C9, CYP2D6 and CYP2C19 isoenzyme were not inhibited by ZINC64450313. Toxicity assay of ZINC64450313 was acquired with an average similarity index of 33.25% and prediction accuracy of 23% on the ProTox-II webserver. The lead molecule has an LD50 value of 10 mg/kg and belongs to toxicity class 2. The frontier molecular orbital's analysis revealed that ZINC64450313 is more reactive than ribavirin due to the possesion of better quantum chemical indices such as its the global hardness. Hence, an in vitro and in vivo assay of these molecules may proffer a pathway to finding effective inhibitors with the potential to truncate functional proteins responsible for the viral life cycle of arenaviruses Lassa.
Communication in Physical Sciences 2020, 5(3): 391-402, 2020
The devastating impact of viral haemorrhagic fevers has deeply been felt in South America and Afr... more The devastating impact of viral haemorrhagic fevers has deeply been felt in South America and Africa. This fever is caused by the arenaviruses Lassa and has posed a matchless fight. Meanwhile, no effective drug or vaccine has been reported. Here we used virtual screening and molecular docking approach to identify a series of novel inhibitors (ZINC64450313 (-10.7 kcal/mol), ZINC00658482 (-10.5 kcal/mol), ZINC40789449 (-10.5 kcal/mol), ZINC14551223 (10.0 kcal/mol) and ZINC73892903 (10.0 kcal/mol)) that can exhibit significant binding affinity to Lassa fever nucleoprotein (PDB ID: 3mx5) than ribavirin (-6.7 kcal/mol). Swiss ADME web tools were used to assess the pharmacokinetics and drug-likeness characteristics of the lead molecule (ZINC64450313). This assay showed that ZINC64450313 obeyed Lipinski, Egan, Verber and Muegge rules. However, pharmacokinetics predictions indicated that CYP1A2, CYP2C9, CYP2D6 and CYP2C19 isoenzyme were not inhibited by ZINC64450313. Toxicity assay of ZINC64450313 was acquired with an average similarity index of 33.25% and prediction accuracy of 23% on the ProTox-II webserver. The lead molecule has an LD50 value of 10 mg/kg and belongs to toxicity class 2. The frontier molecular orbital's analysis revealed that ZINC64450313 is more reactive than ribavirin due to the possesion of better quantum chemical indices such as its the global hardness. Hence, an in vitro and in vivo assay of these molecules may proffer a pathway to finding effective inhibitors with the potential to truncate functional proteins responsible for the viral life cycle of arenaviruses Lassa.