scholarly journals A Compendium of Kinetic Cell Death Modulatory Profiles Identifies Ferroptosis Regulators

2019 ◽  
Author(s):  
Megan Conlon ◽  
Carson Poltorack ◽  
Giovanni C. Forcina ◽  
Alex Wells ◽  
Melodie Mallais ◽  
...  
Keyword(s):  
Cell Death ◽  
Amino Acid ◽  
Small Molecules ◽  
Mtor Inhibitors ◽  
Bioactive Compound ◽  
Time Lapse ◽  
Approved Drugs ◽  
Amino Acid Sensing ◽  
Investigational Agents ◽  
Fda Approved Drugs

AbstractCell death can be executed by regulated apoptotic and non-apoptotic pathways, including the iron-dependent process of ferroptosis. Small molecules are essential tools for studying the regulation of cell death. Using live-cell, time-lapse imaging, and a library of 1,833 small molecules including FDA-approved drugs and investigational agents, we assemble a large compendium of kinetic cell death ‘modulatory profiles’ for inducers of apoptosis and ferroptosis. From this dataset we identified dozens of small molecule inhibitors of ferroptosis, including numerous investigational and FDA-approved drugs with unexpected off-target antioxidant or iron chelating activities. ATP-competitive mechanistic target of rapamycin (mTOR) inhibitors, by contrast, were on-target ferroptosis inhibitors. Further investigation revealed both mTOR-dependent and mTOR-independent mechanisms linking amino acid levels to the regulation of ferroptosis sensitivity in cancer cells. These results highlight widespread bioactive compound pleiotropy and link amino acid sensing to the regulation of ferroptosis.

scholarly journals Emerging Therapeutic Modalities against COVID-19

2020 ◽  
Vol 13 (8) ◽  
pp. 188 ◽  
Author(s):  
Shipra Malik ◽  
Anisha Gupta ◽  
Xiaobo Zhong ◽  
Theodore P. Rasmussen ◽  
Jose E. Manautou ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Small Molecules ◽  
Therapeutic Interventions ◽  
Pharmaceutical Companies ◽  
The Novel ◽  
Comprehensive Overview ◽  
Therapeutic Modalities ◽  
Academic Researchers ◽  
Approved Drugs ◽  
Fda Approved Drugs

The novel SARS-CoV-2 virus has quickly spread worldwide, bringing the whole world as well as the economy to a standstill. As the world is struggling to minimize the transmission of this devastating disease, several strategies are being actively deployed to develop therapeutic interventions. Pharmaceutical companies and academic researchers are relentlessly working to investigate experimental, repurposed or FDA-approved drugs on a compassionate basis and novel biologics for SARS-CoV-2 prophylaxis and treatment. Presently, a tremendous surge of COVID-19 clinical trials are advancing through different stages. Among currently registered clinical efforts, ~86% are centered on testing small molecules or antibodies either alone or in combination with immunomodulators. The rest ~14% of clinical efforts are aimed at evaluating vaccines and convalescent plasma-based therapies to mitigate the disease's symptoms. This review provides a comprehensive overview of current therapeutic modalities being evaluated against SARS-CoV-2 virus in clinical trials.

scholarly journals Computational Search for Potential COVID-19 Drugs from FDA-Approved Drugs and Small Molecules of Natural Origin Identifies Several Anti-Virals and Plant Products

2020 ◽  
Author(s):  
Abhishek Sharma ◽  
Vikas Tiwari ◽  
Ramanathan Sowdhamini
Keyword(s):  
Molecular Dynamics ◽  
Small Molecules ◽  
Natural Origin ◽  
Drug Identification ◽  
The World ◽  
Computational Search ◽  
Simple Molecules ◽  
Human Coronaviruses ◽  
Approved Drugs ◽  
Fda Approved Drugs

<div>The world is facing COVID-19 pandemic at the present time, for which mild symptoms include fever and dry cough. In severe cases it could lead to pneumonia and ultimately death in some instances. The pathogen, SARS-CoV-2, is one of the human coronaviruses which was identified to infect humans first in December 2019. We have interrogated the capacity to repurpose around 2300 FDA-approved drugs and more than 300,000 small molecules of natural origin towards drug identification through virtual screening and molecular dynamics. Interestingly, we observed simple molecules like lactose, previously known anti-virals and few secondary metabolites of plants as promising hits.</div><div><br></div><div></div>

Drug discovery of small molecules for the treatment of COVID-19: A review on clinical studies

2020 ◽  
Vol 21 ◽  
Author(s):  
Bharat Goel ◽  
Nivedita Bhardwaj ◽  
Nancy Tripathi ◽  
Shreyans K. Jain
Keyword(s):  
Small Molecules ◽  
Clinical Studies ◽  
Ebola Virus ◽  
Viral Infections ◽  
New Drugs ◽  
Zoonotic Virus ◽  
Traditional Medicines ◽  
Novel Coronavirus ◽  
Approved Drugs ◽  
Fda Approved Drugs

: Recently, a sudden outbreak of novel coronavirus disease (COVID-19) was caused by a zoonotic virus known as severe acute respiratory syndrome coronavirus (SARS-CoV-2). It has caused pandemic situations around the globe and affecting the lives of millions of people. So far, no drug has been approved for the treatment of SARS-CoV-2 infected patients. As of now, more than 1000 clinical trials are going on for repurposing of FDA approved drugs and for evaluating the safety & efficiency of experimental antiviral molecules to combat COVID-19. Since the development of new drugs may require months to years to reach the market, this review focusses on the potentials of existing small molecule FDA approved drugs and the molecules already in the clinical pipeline against viral infections like HIV, hepatitis B, Ebola virus, and other viruses of coronavirus family (SARS-CoV and MERS-CoV). The review also discusses the natural products and traditional medicines in clinical studies against COVID-19. Currently, 1978 studies are active, 143 completed and 4 posted results (as on June 13, 2020) on clinicaltrials.gov.

scholarly journals Ceftazidime Is a Potential Drug to Inhibit SARS-CoV-2 Infection In Vitro by Blocking Spike Protein-ACE2 Interaction

2020 ◽  
Author(s):  
ChangDong Lin ◽  
Yue Li ◽  
MengYa Yuan ◽  
MengWen Huang ◽  
Cui Liu ◽  
...  
Keyword(s):  
Small Molecules ◽  
High Throughput Screening ◽  
Inhibitory Concentration ◽  
Cell Entry ◽  
Host Cells ◽  
First Line ◽  
Angiotensin Converting Enzyme 2 ◽  
Approved Drugs ◽  
Fda Approved Drugs

SUMMARYCoronavirus Disease 2019 (COVID-19) spreads globally as a sever pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cell entry of SARS-CoV-2 mainly depends on binding of the viral spike (S) proteins to angiotensin converting enzyme 2 (ACE2) on host cells. Therefore, repurposing of known drugs to inhibit S protein-ACE2 interaction could be a quick way to develop effective therapy for COVID-19. Using a high-throughput screening system to investigate the interaction between spike receptor binding domain (S-RBD) and ACE2 extracellular domain, we screened 3581 FDA-approved drugs and natural small molecules and identified ceftazidime as a potent compound to inhibit S-RBD–ACE2 interaction by binding to S-RBD. In addition to significantly inhibit S-RBD binding to HPAEpiC cells, ceftazidime efficiently prevented SARS-CoV-2 pseudovirus to infect ACE2-expressing 293T cells. The inhibitory concentration (IC50) was 113.2 μM, which is far below the blood concentration (over 300 μM) of ceftazidime in patients when clinically treated with recommended dose. Notably, ceftazidime is a drug clinically used for the treatment of pneumonia with minimal side effects compared with other antiviral drugs. Thus, ceftazidime has both anti-bacterial and anti-SARS-CoV-2 effects, which should be the first-line antibiotics used for the clinical treatment of COVID-19.

Photoaffinity Labelling Strategies for Mapping the Small Molecule-Protein Interactome

2021 ◽  
Author(s):  
Nikolas R Burton ◽  
Phillip Kim ◽  
Keriann M. Backus
Keyword(s):  
Small Molecules ◽  
Small Molecule ◽  
Atomic Level ◽  
Photoaffinity Labelling ◽  
Protein Interactome ◽  
Approved Drugs ◽  
Fda Approved Drugs

Nearly all FDA approved drugs and bioactive small molecules exert their effects by binding to and modulating proteins. Consequently, understanding how small molecules interact with proteins at an atomic level...

scholarly journals Small molecules with antiviral activity against the Ebola virus

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 38 ◽  
Author(s):  
Nadia Litterman ◽  
Christopher Lipinski ◽  
Sean Ekins
Keyword(s):  
Small Molecules ◽  
Ebola Virus ◽  
Research Community ◽  
Effective Vaccine ◽  
Emerging Viruses ◽  
Efficacy Data ◽  
Antiviral Compounds ◽  
Recent Outbreak ◽  
Approved Drugs ◽  
Fda Approved Drugs

The recent outbreak of the Ebola virus in West Africa has highlighted the clear shortage of broad-spectrum antiviral drugs for emerging viruses. There are numerous FDA approved drugs and other small molecules described in the literature that could be further evaluated for their potential as antiviral compounds. These molecules are in addition to the few new antivirals that have been tested in Ebola patients but were not originally developed against the Ebola virus, and may play an important role as we await an effective vaccine. The balance between using FDA approved drugs versus novel antivirals with minimal safety and no efficacy data in humans should be considered. We have evaluated 55 molecules from the perspective of an experienced medicinal chemist as well as using simple molecular properties and have highlighted 16 compounds that have desirable qualities as well as those that may be less desirable. In addition we propose that a collaborative database for sharing such published and novel information on small molecules is needed for the research community studying the Ebola virus.

scholarly journals Computational Search for Potential COVID-19 Drugs from FDA-Approved Drugs and Small Molecules of Natural Origin Identifies Several Anti-Virals and Plant Products

2020 ◽  
Author(s):  
Abhishek Sharma ◽  
Vikas Tiwari ◽  
Ramanathan Sowdhamini
Keyword(s):  
Molecular Dynamics ◽  
Small Molecules ◽  
Natural Origin ◽  
Drug Identification ◽  
The World ◽  
Computational Search ◽  
Simple Molecules ◽  
Human Coronaviruses ◽  
Approved Drugs ◽  
Fda Approved Drugs

<div>The world is facing COVID-19 pandemic at the present time, for which mild symptoms include fever and dry cough. In severe cases it could lead to pneumonia and ultimately death in some instances. The pathogen, SARS-CoV-2, is one of the human coronaviruses which was identified to infect humans first in December 2019. We have interrogated the capacity to repurpose around 2300 FDA-approved drugs and more than 300,000 small molecules of natural origin towards drug identification through virtual screening and molecular dynamics. Interestingly, we observed simple molecules like lactose, previously known anti-virals and few secondary metabolites of plants as promising hits.</div><div><br></div><div></div>

Comparing the Metabolome of a Caribbean Sponge to 420 FDA Approved Drugs, a Molecular Networking Approach

Planta Medica ◽  
2013 ◽  
Vol 79 (10) ◽  
Author(s):  
H Houson ◽  
J Schlesser ◽  
J Beverage ◽  
V Macherla ◽  
E Esquenazi
Keyword(s):  
Molecular Networking ◽  
Approved Drugs ◽  
Fda Approved Drugs
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