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

Vaccines ◽  
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.

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

2020 ◽  
Vol 27 ◽  
Author(s):  
Firoz Anwar ◽  
Salma Naqvi ◽  
Fahad A. Al-Abbasi ◽  
Nauroz Neelofar ◽  
Vikas Kumar ◽  
...  
Keyword(s):  
Day Treatment ◽  
Treatment Options ◽  
Developed Countries ◽  
Methyl Transferase ◽  
Comt Inhibitors ◽  
Mao B ◽  
Pharmacokinetic Properties ◽  
Us Fda ◽  
Approved Drugs ◽  
Fda Approved Drugs

: 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.

In Silico Identification of Active Phytochemicals against COVID-19 by Targeting the SARS-CoV-2 Spike Glycoprotein Through Molecular Docking: A Drug Repurposing Approach

2021 ◽  
Vol 8 (2) ◽  
pp. 72-87
Author(s):  
Rathan Kumar
Keyword(s):  
Molecular Docking ◽  
Antiviral Treatment ◽  
Drug Repurposing ◽  
Modern Human ◽  
Binding Affinities ◽  
In Silico Identification ◽  
Adme Properties ◽  
Approved Drugs ◽  
Fda Approved Drugs ◽  
Natural Inhibitors

The spread of coronavirus disease (COVID-19) has become one of the most significant pandemics in modern human history, affecting more than 70 million people worldwide. Currently, only a few fda-approved drugs have suggested fighting the infection, in the absence of a specific antiviral treatment. Thus, repurposing the presently available drugs or using plant-based bioactive compounds can be the fastest possible solution. In this study, the computational methodology of molecular docking techniques was performed to screen and identify the viable potent inhibitors against the SARS-CoV-2 spike protein from a library of 200 active phytochemicals, based on their highest binding affinity towards the target protein. Later, the binding affinities of these phytochemicals were compared with that of the fda-approved drug fluvoxamine, which is currently in use against the mild COVID-19 patients. Out of these, 86 phytochemicals that exhibited better binding energy of value ≤-7.00kcal/mol, is selected for adme (absorption, distribution, metabolism, and excretion) analysis and drug likeliness studies to check the feasibility of these compounds. Wherein, 79 out of 86 phytochemicals showed a better theoretical affinity with sufficiently bearable adme properties. Thus, they can be the lead molecule for further investigation and validation processes towards developing natural inhibitors against the SARS-CoV-2 virus.

scholarly journals Computational Drug Repurposing Studies on SARS-CoV-2 Protein Targets

2020 ◽  
Author(s):  
Guangfeng Zhou ◽  
Lance Stewart ◽  
Gabriella Reggiano ◽  
Frank DiMaio
Keyword(s):  
Experimental Validation ◽  
Rna Binding ◽  
Drug Repurposing ◽  
Protein Targets ◽  
Priority List ◽  
Computational Docking ◽  
Docking Protocol ◽  
Approved Drugs ◽  
Aids Drugs ◽  
Fda Approved Drugs

To contribute to the combat of COVID-2019, we applied structure-based computational docking screens using flexible docking protocol of Rosetta GALigandDock against multiple potential SARS-CoV-2 protein targets, including the Nsp5 3-chymotrypsin-like protease (3CLpro), the Nsp3 ADP ribose phosphatase, the Nsp15 Endoribonuclease, the RNA binding domain of nucleocapsid phosphoprotein, the Nsp16 2'-O-MTase, Nsp14, and Nsp12 RNA-dependent RNA polymerase. Screening against a re-purposing library of 8,395 FDA approved drugs at various stages of drug development and various natural products from DrugBank, we found a total of 124 putative inhibitors with predicted binding ∆G less than -8.9 kcal/mol, including HIV-AIDS drugs Nelfinavir and Tipranavir, targeting 3Clpro with ∆G=-18.8 kcal/mol and ∆G=-16.6 kcal/mol respectively. These primarily involve binders to the Nsp5 3CLpro (37 hits) and the Nsp3 ADP ribose phosphatase (36 hits), with smaller numbers of hits to other targets. These small molecule putative inhibitors suggest a possible avenue for drug repurposing, and the identified compounds should serve as a high-priority list for experimental validation via co-crystallization, enzymatic and cell based assays.

scholarly journals Computational Drug Repurposing Studies on SARS-CoV-2 Protein Targets

2020 ◽  
Author(s):  
Guangfeng Zhou ◽  
Lance Stewart ◽  
Gabriella Reggiano ◽  
Frank DiMaio
Keyword(s):  
Experimental Validation ◽  
Rna Binding ◽  
Drug Repurposing ◽  
Protein Targets ◽  
Priority List ◽  
Computational Docking ◽  
Docking Protocol ◽  
Approved Drugs ◽  
Aids Drugs ◽  
Fda Approved Drugs

To contribute to the combat of COVID-2019, we applied structure-based computational docking screens using flexible docking protocol of Rosetta GALigandDock against multiple potential SARS-CoV-2 protein targets, including the Nsp5 3-chymotrypsin-like protease (3CLpro), the Nsp3 ADP ribose phosphatase, the Nsp15 Endoribonuclease, the RNA binding domain of nucleocapsid phosphoprotein, the Nsp16 2'-O-MTase, Nsp14, and Nsp12 RNA-dependent RNA polymerase. Screening against a re-purposing library of 8,395 FDA approved drugs at various stages of drug development and various natural products from DrugBank, we found a total of 124 putative inhibitors with predicted binding ∆G less than -8.9 kcal/mol, including HIV-AIDS drugs Nelfinavir and Tipranavir, targeting 3Clpro with ∆G=-18.8 kcal/mol and ∆G=-16.6 kcal/mol respectively. These primarily involve binders to the Nsp5 3CLpro (37 hits) and the Nsp3 ADP ribose phosphatase (36 hits), with smaller numbers of hits to other targets. These small molecule putative inhibitors suggest a possible avenue for drug repurposing, and the identified compounds should serve as a high-priority list for experimental validation via co-crystallization, enzymatic and cell based assays.

Structural Basis of Antisickling Effects of Selected FDA Approved Drugs: A Drug Repurposing Study

2018 ◽  
Vol 14 (2) ◽  
pp. 106-116 ◽  
Author(s):  
Olujide O. Olubiyi ◽  
Maryam O. Olagunju ◽  
James O. Oni ◽  
Abidemi O. Olubiyi
Keyword(s):  
Drug Repurposing ◽  
Structural Basis ◽  
Approved Drugs ◽  
Fda Approved Drugs

scholarly journals Screening of an FDA-Approved Library for Novel Drugs against Y. pestis

Antibiotics ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 40
Author(s):  
David Gur ◽  
Theodor Chitlaru ◽  
Emanuelle Mamroud ◽  
Ayelet Zauberman
Keyword(s):  
Drug Repurposing ◽  
Mortality Rates ◽  
Systematic Screening ◽  
Antibiotic Resistant ◽  
Gram Negative ◽  
Therapy Initiation ◽  
Novel Drugs ◽  
Resistant Strains ◽  
Approved Drugs ◽  
Fda Approved Drugs

Yersinia pestis is a Gram-negative pathogen that causes plague, a devastating disease that kills millions worldwide. Although plague is efficiently treatable by recommended antibiotics, the time of antibiotic therapy initiation is critical, as high mortality rates have been observed if treatment is delayed for longer than 24 h after symptom onset. To overcome the emergence of antibiotic resistant strains, we attempted a systematic screening of Food and Drug Administration (FDA)-approved drugs to identify alternative compounds which may possess antibacterial activity against Y. pestis. Here, we describe a drug-repurposing approach, which led to the identification of two antibiotic-like activities of the anticancer drugs bleomycin sulfate and streptozocin that have the potential for designing novel antiplague therapy approaches. The inhibitory characteristics of these two drugs were further addressed as well as their efficiency in affecting the growth of Y. pestis strains resistant to doxycycline and ciprofloxacin, antibiotics recommended for plague treatment.

In Silico Modeling of FDA-Approved Drugs for Discovery of Therapies Against Neglected Diseases: A Drug Repurposing Approach

2019 ◽  
pp. 625-648 ◽  
Author(s):  
Carolina L. Belllera ◽  
María L. Sbaraglini ◽  
Lucas N. Alberca ◽  
Juan I. Alice ◽  
Alan Talevi
Keyword(s):  
In Silico ◽  
Drug Repurposing ◽  
Neglected Diseases ◽  
In Silico Modeling ◽  
Approved Drugs ◽  
Fda Approved Drugs

scholarly journals Immunotherapy in hematological malignancies: recent advances and open questions

Immunotherapy ◽  
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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