scholarly journals Network Pharmacology Analysis of Orally Bioavailable SARS-CoV-2 Protease Inhibitor Shows Synergistic Targets to Improve Clinical Efficacy

2021 ◽  
Vol 7 (2) ◽  
pp. 21-24
Author(s):  
Arun HS Kumar
Keyword(s):  
Protease Inhibitor ◽  
Clinical Efficacy ◽  
Network Pharmacology ◽  
Orally Bioavailable

scholarly journals Network Pharmacology analysis of orally bioavailable SARS-COV2 protease inhibitor shows synergistic targets to improve clinical efficacy

2021 ◽  
Author(s):  
Arun Kumar
Keyword(s):  
Protease Inhibitor ◽  
Clinical Efficacy ◽  
Synergistic Effects ◽  
Network Pharmacology ◽  
Human Tissues ◽  
Inhibitory Effects ◽  
Safety And Efficacy ◽  
Viral Proteases ◽  
Potential Safety ◽  
Orally Bioavailable

Abstract Introduction: Orally bioavailable SARS-CoV2 antiviral drugs will significantly improve the clinical management of the disease. PF07321332 (PF32) one such orally bioavailable SARS-CoV2 protease inhibitor which can be helpful to prevent viral replication in the host. Material and methods: Hence this study evaluated the network pharmacology of PF32 using established methods to predict its potential safety and efficacy. Results: PF32 was selective against SARS-CoV2 proteases without any affinity against SARS-CoV2 RNA polymerase or its spike protein. While PF32 showed pharmacologically relevant affinity against several targets in human tissues. The target profiling of PF32 indicated a fourfold selectivity towards several proteases in human tissues with an affinity (IC50) ranging from 26 to 41 nM. Conclusion: The predicted inhibitory effects of PF32 against both host and viral proteases may have synergistic effects for superior clinical efficacy.

L-735,524: The Design of a Potent and Orally Bioavailable HIV Protease Inhibitor

1994 ◽  
Vol 37 (21) ◽  
pp. 3443-3451 ◽  
Author(s):  
Bruce D. Dorsey ◽  
Rhonda B. Levin ◽  
Stacy L. McDaniel ◽  
Joseph P. Vacca ◽  
James P. Guare ◽  
...  
Keyword(s):  
Protease Inhibitor ◽  
Hiv Protease ◽  
Hiv Protease Inhibitor ◽  
Orally Bioavailable

scholarly journals The Clinical Efficiency and the Mechanism of Sanzi Yangqin Decoction for Chronic Obstructive Pulmonary Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-21
Author(s):  
Mengqi Wang ◽  
Wenwen Gu ◽  
Fuguang Kui ◽  
Fan Gao ◽  
Yuji Niu ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Molecular Docking ◽  
Pulmonary Disease ◽  
Clinical Efficacy ◽  
Network Pharmacology ◽  
Control Group ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Volume Percentage ◽  
The Core

This work is carried out to evaluate the clinical efficacy of Sanzi Yangqin decoction (SZYQD) treating chronic obstructive pulmonary disease (COPD) and to analyze its mechanism. The clinical efficacy of SZYQD treating COPD was evaluated by meta-analysis, and its mechanism was analyzed by network pharmacology. Molecular docking validation of the main active compounds and the core targets was performed by AutoDock vina software. A cigarette smoke (CS) and LPS-induced COPD model in ICR mice was constructed to confirm the effects of luteolin on COPD. Results showed that SZYQD has a greater benefit on the total effect (OR = 3.85, 95% CI [3.07, 4.83], P = 1 ) in the trial group compared with the control group. The percentage of forced expiratory volume in one second (FEV1%) (MD = 0.5, 95% CI [0.41, 0.59], P < 0.00001 ) and first seconds breathing volume percentage of forced vital capacity (FEV1%/FVC) were improved (MD = 5.97, 95% CI [3.23, 8.71], P < 0.00001 ). There are 27 compounds in SZYQD targeting 104 disease targets related to COPD. PPI network analysis indicated that EGFR, MMP9, PTGS2, MMP2, APP, and ERBB2 may be the core targets for the treatment of COPD. Molecular docking demonstrated that luteolin in SZYQD showed the strongest binding activity to core targets. Experimental results revealed that the expression of COPD-related targets in lung tissue was significantly increased in the COPD group and was improved in the luteolin group. Our data indicated that SZYQD has a curative effect on COPD and luteolin is a candidate compound for COPD treatment by regulating EGFR, MMP9, PTGS2, MMP2, APP, and ERBB2.

scholarly journals L-735,524: an orally bioavailable human immunodeficiency virus type 1 protease inhibitor.

1994 ◽  
Vol 91 (9) ◽  
pp. 4096-4100 ◽  
Author(s):  
J. P. Vacca ◽  
B. D. Dorsey ◽  
W. A. Schleif ◽  
R. B. Levin ◽  
S. L. McDaniel ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Protease Inhibitor ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Immunodeficiency Virus ◽  
Orally Bioavailable

New therapeutic agents in the management of HIV: an overview of darunavir for clinicians

Sexual Health ◽  
2008 ◽  
Vol 5 (3) ◽  
pp. 235 ◽  
Author(s):  
Jessica Rotty ◽  
Jennifer Hoy
Keyword(s):  
Side Effects ◽  
Hiv Infection ◽  
Protease Inhibitor ◽  
Drug Interactions ◽  
Clinical Efficacy ◽  
Safety Profile ◽  
Therapeutic Agents ◽  
Drug Resistant ◽  
Efficacy Data ◽  
Resistance Profile

This overview will provide the reader with summarised information about darunavir, a new protease inhibitor licenced for the treatment of drug resistant HIV-infection. Darunavir is a promising new drug with good clinical efficacy data and safety profile. In this overview clinicians will be updated on clinical efficacy data, side-effects, resistance profile and drug interactions. The overview should give clinicians a sound understanding of when and how to use this new protease inhibitor in the treatment of HIV-infection.

scholarly journals Clinical Efficacy Evaluation and Potential Mechanism of Zhishe Tongluo Capsule in the Treatment of Cerebral Infarction by Meta-Analysis Associated with Network Pharmacology

2022 ◽  
Vol 2022 ◽  
pp. 1-13
Author(s):  
Zhi Xin Geng ◽  
Feng Gao ◽  
Junjing Guo ◽  
Bingzhou Guo ◽  
Chunyu Liu ◽  
...  
Keyword(s):  
Treatment Group ◽  
Cerebral Infarction ◽  
Clinical Efficacy ◽  
Large Scale ◽  
Chemical Constituents ◽  
English Literature ◽  
Controlled Trial ◽  
Meta Analysis ◽  
Network Pharmacology ◽  
Control Group

Objective. By integrating meta-analysis and network pharmacology strategy, the clinical efficacy of Zhishe Tongluo capsule in the treatment of cerebral infarction was evaluated, and the intervention mechanism was preliminary explored. Methods. Through meta-analysis, the Chinese and English literature of the randomized controlled trial (RCT) of Zhishe Tongluo capsule in the treatment of cerebral infarction was comprehensively searched. Based on the standard of Na Pai, the quantitative literature was determined and the Review Manager data were statistically analyzed. Results. A total of 10 RCTs literatures were included. These literatures included a total of 1278 subjects, of which 670 were in the treatment group and 608 were in the control group. In terms of indicators of efficiency and adverse reaction rate, the treatment group was better than the control group. There was a statistical difference P < 0.05 ; a total of 559 chemical constituents and 2306 potential targets were obtained from the online database. Of these, 201 components, 145 targets, and 185 pathways were closely related to cerebral infarction. Conclusions. The available evidence indicates that the addition of Zhishe Tongluo capsule to the conventional treatment of Western medicine can improve the clinical efficacy of cerebral infarction and has some advantages in regulating blood lipids and hemorheology, but the overall evidence level is low, which still needs to be further supported by large-scale and multicenter RCTs; intervention of brain infarction by Zhishe Tongluo capsule is a comprehensive result of multicomponent and multi-target interactions. On the basis of the combined meta-analysis and network pharmacology in scientific attempts, it also provides a reference for the clinical evaluation of other drugs and mechanism research.

Tipranavir (PNU-140690):  A Potent, Orally Bioavailable Nonpeptidic HIV Protease Inhibitor of the 5,6-Dihydro-4-hydroxy-2-pyrone Sulfonamide Class∇

1998 ◽  
Vol 41 (18) ◽  
pp. 3467-3476 ◽  
Author(s):  
Steve R. Turner ◽  
Joseph W. Strohbach ◽  
Ruben A. Tommasi ◽  
Paul A. Aristoff ◽  
Paul D. Johnson ◽  
...  
Keyword(s):  
Protease Inhibitor ◽  
Hiv Protease ◽  
Hiv Protease Inhibitor ◽  
Orally Bioavailable
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