Targeting COVID-19 in Parkinson’s patients: Drugs repurposed.

: The last couple of months have witnessed the world in a state of virtual standstill. The SARS-CoV-2 virus has overtaken globe to economic and social lockdown. Many patients with COVID-19 have compromised immunity, especially in an aged population suffering from Parkinson disease (PD). Alteration in dopaminergic neurons or deficiency of dopamine in PD patients is the most common symptoms affecting 1% population above the age of 60 years. The compromised immune system and inflammatory manifestation in PD patients make them an easy target. The most common under trial drugs for COVID-19 are Remdesivir, Favipiravir, Chloroquine and Hydroxychloroquine, Azithromycin along with adjunct drugs like Amantadine with some monoclonal antibodies. : Presently, clinically US FDA approved drugs in PD includes Levodopa, catechol-O-methyl transferase (COMT) inhibitors, (Entacapone and Tolcapone), Dopamine agonists (Bromocriptine, Ropinirole, Pramipexole, and Rotigotine), Monoamine oxidase B (MAO-B) inhibitors (Selegiline and Rasagiline), Amantadine and Antimuscarinic drugs. The drugs have established mechanism of action on PD patients with known pharmacodynamics and pharmacokinetic properties along with dose and adverse effects. : Conclusion and relevance of this review focus on the drugs that can be tried for the PD patients with SAR CoV-2 infection, in particular, Amantadine approved by all developed countries a common drug possessing both antiviral properties by downregulation of CTSL, lysosomal pathway disturbance and change in pH necessary to uncoat the viral proteins and antiParkinson properties. The significant prognostic adverse effect of SARS-CoV-2 on PD and the present-day treatment options, clinical presentation and various mechanism is warrant need of the hour.

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Multi-Targeted Approaches and Drug Repurposing Reveal Possible SARS-CoV-2 Inhibitors

Vaccines ◽

10.3390/vaccines10010024 ◽

2021 ◽

Vol 10 (1) ◽

pp. 24

Author(s):

Khalid Mashay Alanazi ◽

Mohammad Abul Farah ◽

Yan-Yan Hor

Keyword(s):

Experimental Validation ◽

Computational Analysis ◽

Treatment Options ◽

Drug Repurposing ◽

Binding Affinities ◽

Normal Model ◽

Inhibitory Potential ◽

Us Fda ◽

Approved Drugs ◽

Fda Approved Drugs

The COVID-19 pandemic caused by SARS-CoV-2 is unprecedented in recent memory owing to the non-stop escalation in number of infections and deaths in almost every country of the world. The lack of treatment options further worsens the scenario, thereby necessitating the exploration of already existing US FDA-approved drugs for their effectiveness against COVID-19. In the present study, we have performed virtual screening of nutraceuticals available from DrugBank against 14 SARS-CoV-2 proteins. Molecular docking identified several inhibitors, two of which, rutin and NADH, displayed strong binding affinities and inhibitory potential against SARS-CoV-2 proteins. Further normal model-based simulations were performed to gain insights into the conformational transitions in proteins induced by the drugs. The computational analysis in the present study paves the way for experimental validation and development of multi-target guided inhibitors to fight COVID-19.

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Physicochemical and Pharmacokinetic Properties Determining Drug Detection in Skin

10.1101/2021.08.17.456720 ◽

2021 ◽

Author(s):

Wout Bittremieux ◽

Rohit Advani ◽

Alan K Jarmusch ◽

Shaden Aguirre ◽

Aileen Lu ◽

...

Keyword(s):

Molecular Descriptors ◽

Untargeted Metabolomics ◽

Therapeutic Drug ◽

Drug Detection ◽

Model Interpretation ◽

Drug Classes ◽

Pharmacokinetic Properties ◽

The Mean ◽

Approved Drugs ◽

Fda Approved Drugs

Chemicals, including some systemically administered xenobiotics and their biotransformations, can be detected noninvasively using skin swabs and untargeted metabolomics analysis. We sought to understand the principal drivers that determine whether a drug taken orally or systemically is likely to be observed on the epidermis by using a random forest classifier to predict which drugs would be detected on the skin. A variety of molecular descriptors describing calculated properties of drugs, such as measures of volume, electronegativity, bond energy, and electrotopology, were used to train the classifier. The mean area under the ROC curve was 0.71 for predicting drug detection on the epidermis, and the SHapley Additive exPlanations model interpretation technique was used to determine the most relevant molecular descriptors. Based on the analysis of 2,561 FDA approved drugs, we predict that therapeutic drug classes such as nervous system drugs are more likely to be detected on the skin. Detecting drugs and other chemicals noninvasively on the skin using untargeted metabolomics could be a useful clinical advancement in therapeutic drug monitoring, adherence, and health status.

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Immunotherapy in hematological malignancies: recent advances and open questions

Immunotherapy ◽

10.2217/imt-2021-0065 ◽

2021 ◽

Vol 13 (14) ◽

pp. 1215-1229

Author(s):

Essam A Tawfik ◽

Norah A Aldrak ◽

Shahad H Albrahim ◽

Dunia A Alzahrani ◽

Haya A Alfassam ◽

...

Keyword(s):

Hematological Malignancies ◽

Hematopoietic Malignancy ◽

Hematopoietic Malignancies ◽

The Past ◽

Open Questions ◽

Cell Immunotherapy ◽

Different Types ◽

Us Fda ◽

Approved Drugs ◽

Fda Approved Drugs

Over recent years, tremendous advances in immunotherapy approaches have been observed, generating significant clinical progress. Cancer immunotherapy has been shown, in different types of blood cancers, to improve the overall survival of patients. Immunotherapy treatment of hematopoietic malignancies is a newly growing field that has been accelerating over the past years. Several US FDA approved drugs and cell-based therapies are being exploited in the late stage of clinical trials. This review attempt to highlight and discuss the numerous innovative immunotherapy approaches of hematopoietic malignancy ranging from nonmyeloablative transplantation, T-cell immunotherapy, natural killer cells and immune agonist to monoclonal antibodies and vaccination. In addition, a brief discussion on the future advances and accomplishments required to counterpart the current immunotherapeutic approaches for hematopoietic malignancies were also highlighted.

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Analysis of US FDA-Approved Drugs Containing Sulfur Atoms

Topics in Current Chemistry ◽

10.1007/s41061-018-0184-5 ◽

2018 ◽

Vol 376 (1) ◽

Cited By ~ 124

Author(s):

Kevin A. Scott ◽

Jon T. Njardarson

Keyword(s):

Us Fda ◽

Approved Drugs ◽

Fda Approved Drugs

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Pharmacokinetic drug–drug interactions: an insight into recent US FDA-approved drugs for prostate cancer

Bioanalysis ◽

10.4155/bio-2020-0242 ◽

2020 ◽

Vol 12 (22) ◽

pp. 1647-1664

Author(s):

Siva Nageswara Rao Gajula ◽

Gangireddy Navitha Reddy ◽

Dannarm Srinivas Reddy ◽

Rajesh Sonti

Keyword(s):

Drug Interactions ◽

Therapeutic Index ◽

Aged Patients ◽

Metabolizing Enzymes ◽

Considerable Concentration ◽

Concentration Changes ◽

Us Fda ◽

Approved Drugs ◽

Fda Approved Drugs ◽

Pharmacokinetic Drug

Pharmacokinetic drug–drug interaction is a significant safety and efficiency concern as it results in considerable concentration changes. Drug–drug interactions are a substantial concern in anticancer drugs that possess a narrow therapeutic index. These interactions remain as the principal regulatory obstacle that can lead to termination in the preclinical stage, restrictions in the prescription, dosage adjustments or withdrawal of the drugs from the market. Drug metabolizing enzymes or transporters mediate the majority of clinically relevant drug interactions. Cancer diagnosed aged patients use multiple medications and are more prone to significant drug–drug interactions. This review provides detailed information on clinically relevant drug–drug interactions resulting from drug metabolism by enzymes and transporters with a particular emphasis on recent FDA approved antiprostate cancer drugs.

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COVID-19 pandemic: an overview of epidemiology, pathogenesis, diagnostics and potential vaccines and therapeutics

Therapeutic Delivery ◽

10.4155/tde-2020-0035 ◽

2020 ◽

Vol 11 (4) ◽

pp. 245-268 ◽

Cited By ~ 22

Author(s):

Haneen Amawi ◽

Ghina'a I Abu Deiab ◽

Alaa A A Aljabali ◽

Kamal Dua ◽

Murtaza M Tambuwala

Keyword(s):

Middle East ◽

Clinical Evaluation ◽

Preventive Measures ◽

Vaccine Development ◽

Us Fda ◽

Approved Drugs ◽

Respiratory Coronavirus ◽

Fda Approved Drugs

At the time of writing this review, severe acute respiratory coronavirus syndrome-2 (SARS-CoV-2) has infected more than 2,355,853 patients and resulted in more than 164,656 deaths worldwide (as of 20 April 2020). This review highlights the preventive measures, available clinical therapies and the potential of vaccine development against SARS-CoV-2 by taking into consideration the strong genetic similarities of the 2003 epidemic SARS-CoV. Recent studies are investigating the repurposing of US FDA-approved drugs as there is no available vaccine yet with many attempts under clinical evaluation. Several antivirals, antimalarials and immunomodulators that have shown activity against SARS-CoV and Middle East coronavirus respiratory syndromes are being evaluated. In particular, hydroxychloroquine, remdesivir, favipiravir, arbidol, tocilizumab and bevacizumab have shown promising results. The main aim of this review is to provide an overview of this pandemic and where we currently stand.

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Re-Profiling of US-FDA Approved Drugs for COVID-19 by In-silico Studies

Journal of Bioinformatics and Systems Biology ◽

10.26502/jbsb.5107021 ◽

2021 ◽

Vol 04 (02) ◽

Author(s):

Akash Parab ◽

Dr Gaganjyot Kaur ◽

Abhishek Sharma ◽

Gursewak Bhuller ◽

Sharvari Chitnis ◽

...

Keyword(s):

In Silico ◽

In Silico Studies ◽

Us Fda ◽

Approved Drugs ◽

Fda Approved Drugs

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TMPRSS2 Transcriptional Inhibition as a Therapeutic Strategy for COVID-19

10.20944/preprints202003.0360.v2 ◽

2020 ◽

Cited By ~ 1

Author(s):

Xinchen Wang ◽

Ryan Dhindsa ◽

Gundula Povysil ◽

Anthony Zoghbi ◽

Joshua Motelow ◽

...

Keyword(s):

Viral Entry ◽

Therapeutic Strategy ◽

Treatment Options ◽

Human Populations ◽

Expression Data ◽

Transcriptional Inhibition ◽

Transcriptional Modulators ◽

Approved Drugs ◽

Fda Approved Drugs ◽

Therapeutic Avenue

There is an urgent need to identify effective therapies for COVID-19. The SARS-CoV-2 host factor protease TMPRSS2 is required for viral entry and thus an attractive target for therapeutic intervention. In mouse, knockout of tmprss2 led to protection against SARS-CoV-1 with no deleterious phenotypes, and in human populations genetic loss of TMPRSS2 does not appear to be selected against. Here, we mined publicly available gene expression data to identify several compounds that down-regulate TMPRSS2. Recognizing the need for immediately available treatment options, we focused on FDA-approved drugs. We found 20 independent studies that implicate estrogenic and androgenic compounds as transcriptional modulators of TMPRSS2, suggesting these classes of drugs may be promising therapeutic candidates for clinical testing and observational studies of COVID-19. We also note that expression of TMPRSS2 is highly variable and skewed in humans, with a minority of individuals having extremely high expression. Combined with literature showing that inhibition of TMPRSS2 protease activity reduces SARS-CoV-2 viral entry in human cells, our results raise the hypothesis that modulation of TMPRSS2 expression is a promising therapeutic avenue for COVID-19.

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Privileged Pharmacophore of FDA Approved Drugs in Combination with Chalcone Framework: A New Hope for Alzheimer’s Treatment

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207323999200728122627 ◽

2020 ◽

Vol 23 (9) ◽

pp. 842-846

Author(s):

Bijo Mathew

Keyword(s):

Drug Design ◽

Monoamine Oxidase ◽

Functional Design ◽

Mao B ◽

Structural Framework ◽

Current Perspective ◽

Design Paradigm ◽

Dual Inhibition ◽

Approved Drugs ◽

Fda Approved Drugs

Multi-functional design of ligands emerged as a new drug design paradigm of Alzheimer’s disease (AD). Given the complexity of AD, the molecules showing dual inhibition of monoamine oxidase (MAO) and acetylcholinesterase (AChE) with neuroprotective properties could prevent the progressive neural degeneration effectively. Numerous studies documented that chalcone is a privileged structural framework for the inhibition of both MAO and AChE. The recent studies suggested that the development of chalcone candidates endowed with pharmacophores of FDA approved drugs may become an active molecules in the field of current AD research. The current perspective described the recent updates of chalcone moiety linked with the pharmacophores of flurbiprofen and rivastigmine hybrids as selective ChE/MAO-B inhibitors for the prophylactic agents for AD.

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