Background:Recently,the Chinese scientists Liu et al.demonstrated a crystallized form of severe acute respiratory syndrome coronavirus-2 main protease(M^(pro)),the best target of the drug,which was published in Nature...Background:Recently,the Chinese scientists Liu et al.demonstrated a crystallized form of severe acute respiratory syndrome coronavirus-2 main protease(M^(pro)),the best target of the drug,which was published in Nature in June 2020.Many components of herbs are determined as the potential inhibitors of coronavirus disease 2019(COVID-19)M^(pro)such as quercetin,cirsimaritin,hispidulin,and flavonoids.Methods:Library of herb-based bioactive saponins are analyzed with 6LU7 M^(pro)using AutoDock tools 1.5.6,BIOVIA Discovery Studio 2017 R2,Chimera 1.13.1,and AutoDock Vina to evaluate their potency against COVID-19 M^(pro).The conventional Western medicines,including hydroxychloroquine,chloroquine and nelfinavir,are used as positive controls for comparison.Results:Binding energies of 60 saponins with 6LU7 M^(pro)are obtained in which approximately 34 saponins are more effective on COVID-19 M^(pro)than hydroxychloroquine,chloroquine,and nelfinavir.13 saponins exhibit high potency against COVID-19 M^(pro)due to more binding energies than 10 kcal/mol.Conclusion:Further research on all effective saponins is needed to evaluate the real medicinal potential against COVID-19.展开更多
Coronavirus (CoVID-19) is a new outbreak of coronavirus disease which started in the Wuhan, China, the spread of this virus has now reached a global stage, urgent need is therefore needed to find new drug molecules wh...Coronavirus (CoVID-19) is a new outbreak of coronavirus disease which started in the Wuhan, China, the spread of this virus has now reached a global stage, urgent need is therefore needed to find new drug molecules which can either be used as a first aid intervention or slow down the multiplication rate of the virus within the system. In order to address this, this research looked into the existing antiviral drugs and screened them for their inhibitory properties towards the CoVID-19 protein. Recently, the crystal structure of the CoVID-19 (6LU7) protein has been established, this gives us the possible drug target site in CoVID-19. The binding affinity of the six compounds was screened using MOE (Molecular Operating Environment) software, four compounds (Zanamivir, Peramivir, Rimantidine, and Oseltamivir) out these six compounds have been approved by the Food Drug and Administration (FDA). The molecular docking calculation, Higher Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO) calculation were used to hypothesise the bioactivity of the FDA approved drug against the CoVID-19 protein. The calculation showed that Pimodivir tops the list of the anti influenza drug which can be used as first aid treatment for patient. Apart from Pimodivir, Laninamivir Octanoate is also a very good drug which might be used to inhibit CoVID-19 protein. It was also discovered that based on binding property of Rimantadine, it might be suitable for Fragment Based Drug Design (FBDD) approach which might lead to the discovery of completely new drug entity. Stability of the new protein structure was studied using GROMACS molecular dynamic simulation software. The results showed that the stability of the protein structure was achieved over a range of time, this confirmed that 6LU7 crystal structure might be a suitable protein crystal structure suitable for the development of new drug towards the treatment of CoVID-19. Finally, based on the molecular docking result, Pimodivir and Laninamivir Octanoate might be useful in the treatment of infected patient.展开更多
基金National Natural Science Foundation of China under Grants(50772112,90922003,50872135)the Director Foundation of Anhui Institute of Optics and Fine Mechanics
文摘Background:Recently,the Chinese scientists Liu et al.demonstrated a crystallized form of severe acute respiratory syndrome coronavirus-2 main protease(M^(pro)),the best target of the drug,which was published in Nature in June 2020.Many components of herbs are determined as the potential inhibitors of coronavirus disease 2019(COVID-19)M^(pro)such as quercetin,cirsimaritin,hispidulin,and flavonoids.Methods:Library of herb-based bioactive saponins are analyzed with 6LU7 M^(pro)using AutoDock tools 1.5.6,BIOVIA Discovery Studio 2017 R2,Chimera 1.13.1,and AutoDock Vina to evaluate their potency against COVID-19 M^(pro).The conventional Western medicines,including hydroxychloroquine,chloroquine and nelfinavir,are used as positive controls for comparison.Results:Binding energies of 60 saponins with 6LU7 M^(pro)are obtained in which approximately 34 saponins are more effective on COVID-19 M^(pro)than hydroxychloroquine,chloroquine,and nelfinavir.13 saponins exhibit high potency against COVID-19 M^(pro)due to more binding energies than 10 kcal/mol.Conclusion:Further research on all effective saponins is needed to evaluate the real medicinal potential against COVID-19.
文摘Coronavirus (CoVID-19) is a new outbreak of coronavirus disease which started in the Wuhan, China, the spread of this virus has now reached a global stage, urgent need is therefore needed to find new drug molecules which can either be used as a first aid intervention or slow down the multiplication rate of the virus within the system. In order to address this, this research looked into the existing antiviral drugs and screened them for their inhibitory properties towards the CoVID-19 protein. Recently, the crystal structure of the CoVID-19 (6LU7) protein has been established, this gives us the possible drug target site in CoVID-19. The binding affinity of the six compounds was screened using MOE (Molecular Operating Environment) software, four compounds (Zanamivir, Peramivir, Rimantidine, and Oseltamivir) out these six compounds have been approved by the Food Drug and Administration (FDA). The molecular docking calculation, Higher Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO) calculation were used to hypothesise the bioactivity of the FDA approved drug against the CoVID-19 protein. The calculation showed that Pimodivir tops the list of the anti influenza drug which can be used as first aid treatment for patient. Apart from Pimodivir, Laninamivir Octanoate is also a very good drug which might be used to inhibit CoVID-19 protein. It was also discovered that based on binding property of Rimantadine, it might be suitable for Fragment Based Drug Design (FBDD) approach which might lead to the discovery of completely new drug entity. Stability of the new protein structure was studied using GROMACS molecular dynamic simulation software. The results showed that the stability of the protein structure was achieved over a range of time, this confirmed that 6LU7 crystal structure might be a suitable protein crystal structure suitable for the development of new drug towards the treatment of CoVID-19. Finally, based on the molecular docking result, Pimodivir and Laninamivir Octanoate might be useful in the treatment of infected patient.
