Chirality: Pharmacological Action and Drug Development

1990 ◽  
pp. 1-28 ◽  
Author(s):  
MARTHA HYNECK ◽  
JOHN DENT ◽  
JERRY B. HOOK
Keyword(s):  
Drug Development ◽  
Pharmacological Action

scholarly journals Spontaneous Binding of Potential COVID-19 Drugs to Human Serine Protease TMPRSS2

2020 ◽  
Author(s):  
Haixia Zhu ◽  
Wenhao Du ◽  
Menghua Song ◽  
Qing Liu ◽  
Andreas Herrmann ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Drug Development ◽  
Effective Treatment ◽  
Binding Sites ◽  
Molecular Mechanisms ◽  
Pharmacological Action ◽  
Proteolytic Processing ◽  
Proteolytic Activation ◽  
Catalytic Center ◽  
Dynamics Simulations

Effective treatment or vaccine is not yet available for combating SARS coronavirus 2 (SARSCoV-2) that caused the COVID-19 pandemic. Recent studies showed that two drugs, Camostat and Nafamostat, might be repurposed to treat COVID-19 by inhibiting human TMPRSS2 required for proteolytic activation of viral spike (S) glycoprotein. However, their molecular mechanisms of pharmacological action remain unclear. Here, we perform molecular dynamics simulations to investigate their native binding sites on TMPRSS2. We revealed that both drugs could spontaneously and stably bind to the TMPRSS2 catalytic center, and thereby inhibit its proteolytic processing of the S protein. Also, we found that Nafamostat is more specific than Camostat for binding to the catalytic center, consistent with reported observation that Nafamostat blocks the SARS-CoV-2 infection at a lower concentration. Thus, this study provides mechanistic insights into the Camostat and Nafamostat inhibition of the SARS-CoV-2 infection, and offers useful information for COVID-19 drug development.

scholarly journals Spontaneous Binding of Potential COVID-19 Drugs to Human Serine Protease TMPRSS2

2020 ◽  
Author(s):  
Haixia Zhu ◽  
Wenhao Du ◽  
Menghua Song ◽  
Qing Liu ◽  
Andreas Herrmann ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Drug Development ◽  
Effective Treatment ◽  
Binding Sites ◽  
Molecular Mechanisms ◽  
Pharmacological Action ◽  
Proteolytic Processing ◽  
Proteolytic Activation ◽  
Catalytic Center ◽  
Dynamics Simulations

Effective treatment or vaccine is not yet available for combating SARS coronavirus 2 (SARSCoV-2) that caused the COVID-19 pandemic. Recent studies showed that two drugs, Camostat and Nafamostat, might be repurposed to treat COVID-19 by inhibiting human TMPRSS2 required for proteolytic activation of viral spike (S) glycoprotein. However, their molecular mechanisms of pharmacological action remain unclear. Here, we perform molecular dynamics simulations to investigate their native binding sites on TMPRSS2. We revealed that both drugs could spontaneously and stably bind to the TMPRSS2 catalytic center, and thereby inhibit its proteolytic processing of the S protein. Also, we found that Nafamostat is more specific than Camostat for binding to the catalytic center, consistent with reported observation that Nafamostat blocks the SARS-CoV-2 infection at a lower concentration. Thus, this study provides mechanistic insights into the Camostat and Nafamostat inhibition of the SARS-CoV-2 infection, and offers useful information for COVID-19 drug development.

scholarly journals Flipping the odds of drug development success through human genomics

2017 ◽  
Author(s):  
Aroon D. Hingorani ◽  
Valerie Kuan ◽  
Chris Finan ◽  
Felix A. Kruger ◽  
Anna Gaulton ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Drug Development ◽  
Drug Target ◽  
Molecular Targets ◽  
Pharmacological Action ◽  
Common Disease ◽  
Human Genomics ◽  
Small Molecule Drugs ◽  
Development Failure ◽  
Druggable Targets

AbstractDrug development depends on accurately identifying molecular targets that both play a causal role in a disease and are amenable to pharmacological action by small molecule drugs or bio-therapeutics, such as monoclonal antibodies.Errors in drug target specification contribute to the extremely high rates of drug development failure.Integrating knowledge of genes that encode druggable targets with those that influence susceptibility to common disease has the potential to radically improve the probability of drug development success.

A update of botanical drug development in the United States: Status of applications

Planta Medica ◽  
2015 ◽  
Vol 81 (11) ◽  
Author(s):  
KM Wu ◽  
C Wu ◽  
J Dou ◽  
H Ghantous ◽  
S Lee ◽  
...  
Keyword(s):  
United States ◽  
Drug Development ◽  
The United States ◽  
Botanical Drug

Evaluation of clinical efficacy of Derinat® in form of spray in practice of district therapist

2019 ◽  
Vol 1 (9) ◽  
pp. 38-46
Author(s):  
A. P. Babkin ◽  
A. A. Zuikova ◽  
O. N. Krasnorutskaya ◽  
Yu. A. Kotova ◽  
D. Yu. Bugrimov ◽  
...  
Keyword(s):  
Clinical Efficacy ◽  
Respiratory Diseases ◽  
Viral Infections ◽  
Pharmacological Action ◽  
The Body ◽  
Natural Resistance ◽  
Acute Respiratory Diseases ◽  
T Helpers ◽  
T Killers ◽  
Stimulation Of

The widespread worldwide spread of acute respiratory diseases is an urgent problem in health care. Expressed polyetiology of respiratory diseases does not allow to limit the use of specific vaccine preparations and dictates the need to use to combat them a variety of non-specific means that stimulate the natural resistance of the human body. The main pharmacological action of sodium deoxyribonucleate is the stimulation of phagocytic activity of T-helpers and T-killers, increasing the functional activity of neutrophils and monocytes/ macrophages, providing regeneration and repair processes in the epithelial component of antiviral protection of the body. Based on the above, the study of the clinical efficacy of Derinat® in the form of spray in the treatment of acute respiratory viral infections is relevant.

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