Virtual Screening of an FDA Approved Drugs Database on Two COVID-19 Coronavirus Proteins

10.26434/chemrxiv.11847381 ◽

2020 ◽

Cited By ~ 8

Author(s):

Alessandro Contini

Keyword(s):

Crystal Structure ◽

Virtual Screening ◽

Protease Inhibitors ◽

Virus Replication ◽

World Wide ◽

Hiv Infections ◽

Approved Drugs ◽

Fda Approved Drugs ◽

Homology Models

<div>The infection by the 2019-nCoV coronavirus (COVID-19) is a world-wide emergency.</div><div>The crystal structure of a protein essential for virus replication has been filed in the Protein Data</div><div>Bank recently. Additionally, homology models of 24 COVID-19 proteins were made available by</div><div>the Zhang group. In this paper, we present results deriving from the virtual screening of a database</div><div>of more than 3000 FDA approved drugs on two distinct targets. Results showed that some of the</div><div>known protease inhibitors currently used in HIV infections might be helpful for the therapy of</div><div>COVID-19 also.</div>

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Virtual Screening of FDA Approved Drugs Against Nsp15 Endoribonuclease from SARS CoV-2

10.26434/chemrxiv.13265519 ◽

2020 ◽

Author(s):

Althaf Shaik ◽

Nalini Natarajan ◽

Sivapriya Kirubakaran ◽

Vijay Thiruvenkatam

Keyword(s):

Crystal Structure ◽

Molecular Dynamics ◽

Virtual Screening ◽

Computational Approach ◽

Important Target ◽

Structure Solution ◽

Wet Lab ◽

Approved Drugs ◽

Dynamics Simulations ◽

Fda Approved Drugs

<p>This manuscript shows a detailed computational approach of carefully curated drugs that can potentially act against Nsp15, an endoribonuclease necessary for SARS-CoV2 multiplication. In our work, we have considered maximum resources available on Nsp15 including the recent crystal structure solution of the protein. Owing to the increase in demand for a cure for COVID-19, we have attempted to virtually screen an important target of SARS-CoV2 using the pre-existing FDA approved drugs. The main advantage of our work is our multi-step approach in validating our hits. We have performed initial High Throughput Virtual Screening (HTVS) of 2910 drugs. The top 20 hits were subjected to rigorous molecular docking and molecular dynamics simulations yielding a final number of 5 potential hits. In this global emergency, we have made a humble yet critical attempt by undertaking this work; we hope that our work once published may be of help in carrying out appropriate wet-lab work. </p><p></p>We declare that this manuscript is original, has not been published before and is not currently being considered for publication elsewhere."

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Virtual Screening of FDA Approved Drugs Against Nsp15 Endoribonuclease from SARS CoV-2

10.26434/chemrxiv.13265519.v1 ◽

2020 ◽

Author(s):

Althaf Shaik ◽

Nalini Natarajan ◽

Sivapriya Kirubakaran ◽

Vijay Thiruvenkatam

Keyword(s):

Crystal Structure ◽

Molecular Dynamics ◽

Virtual Screening ◽

Computational Approach ◽

Important Target ◽

Structure Solution ◽

Wet Lab ◽

Approved Drugs ◽

Dynamics Simulations ◽

Fda Approved Drugs

<p>This manuscript shows a detailed computational approach of carefully curated drugs that can potentially act against Nsp15, an endoribonuclease necessary for SARS-CoV2 multiplication. In our work, we have considered maximum resources available on Nsp15 including the recent crystal structure solution of the protein. Owing to the increase in demand for a cure for COVID-19, we have attempted to virtually screen an important target of SARS-CoV2 using the pre-existing FDA approved drugs. The main advantage of our work is our multi-step approach in validating our hits. We have performed initial High Throughput Virtual Screening (HTVS) of 2910 drugs. The top 20 hits were subjected to rigorous molecular docking and molecular dynamics simulations yielding a final number of 5 potential hits. In this global emergency, we have made a humble yet critical attempt by undertaking this work; we hope that our work once published may be of help in carrying out appropriate wet-lab work. </p><p></p>We declare that this manuscript is original, has not been published before and is not currently being considered for publication elsewhere."

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Repositioning of Etravirine as a Potential CK1ε Inhibitor by Virtual Screening

Pharmaceuticals ◽

10.3390/ph15010008 ◽

2021 ◽

Vol 15 (1) ◽

pp. 8

Author(s):

Luis Córdova-Bahena ◽

Axel A. Sánchez-Álvarez ◽

Angel J. Ruiz-Moreno ◽

Marco A. Velasco-Velázquez

Keyword(s):

Molecular Dynamics ◽

Virtual Screening ◽

Noncovalent Interactions ◽

Antineoplastic Agent ◽

Pharmacophore Model ◽

Hiv Infections ◽

Binding Behavior ◽

Approved Drugs ◽

Potential Inhibitors ◽

Fda Approved Drugs

CK1ε is a key regulator of WNT/β-catenin and other pathways that are linked to tumor progression; thus, CK1ε is considered a target for the development of antineoplastic therapies. In this study, we performed a virtual screening to search for potential CK1ε inhibitors. First, we characterized the dynamic noncovalent interactions profiles for a set of reported CK1ε inhibitors to generate a pharmacophore model, which was used to identify new potential inhibitors among FDA-approved drugs. We found that etravirine and abacavir, two drugs that are approved for HIV infections, can be repurposed as CK1ε inhibitors. The interaction of these drugs with CK1ε was further examined by molecular docking and molecular dynamics. Etravirine and abacavir formed stable complexes with the target, emulating the binding behavior of known inhibitors. However, only etravirine showed high theoretical binding affinity to CK1ε. Our findings provide a new pharmacophore for targeting CK1ε and implicate etravirine as a CK1ε inhibitor and antineoplastic agent.

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Mulberrofuran G, a Potent Inhibitor of SPIKE Protein of SARS Corona Virus 2

Journal of Pharmaceutical Care ◽

10.18502/jpc.v9i2.6610 ◽

2021 ◽

Author(s):

Fatemeh Sadat Hosseini ◽

Mohammad Reza Motamedi

Keyword(s):

Molecular Docking ◽

Virtual Screening ◽

Active Site ◽

Potential Role ◽

Potent Inhibitor ◽

Screening Method ◽

Spike Protein ◽

Treatment Agent ◽

Approved Drugs ◽

Fda Approved Drugs

Background: At the onset of the 2020 year, Coronavirus disease (COVID-19) has become a pandemic and infected many people worldwide. Despite all efforts, no cure was found for this infection. Bioinformatics and medicinal chemistry have a potential role in the primary consideration of drugs to treat this infection. With virtual screening and molecular docking, some potent compounds and medications can be found and modified and then applied to treat disease in the next steps. Methods: By virtual screening method and PRYX software, some Food and Drug Administration (FDA) approved drugs and natural compounds have been docked with the SPIKE protein of SARS-CoV-2. Some more potent agents have been selected, and then new structures are designed with better affinity than them. After that, we searched for the molecules with a similar structure to designed compounds to find the most potent compound to our target. Results: Because of the study of structures and affinities, mulberrofuran G was the most potent compound in this study. The compound has interacted strongly with residues in the probably active site of SPIKE. Conclusion: Mulberrofuran G can be a treatment agent candidate for COVID-19 because of its good affinity to SPIKE of the virus and inhibition of virus-cell adhesion and entrance.

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Virtual screening as therapeutic strategy of COVID-19 targeting angiotensin-converting enzyme 2

Frontiers in Molecular Immunology ◽

10.25082/fmi.2021.01.002 ◽

2021 ◽

Vol 2 (1) ◽

pp. 16-27

Author(s):

Zahra Sharifinia ◽

◽

Samira Asadi ◽

Mahyar Irani ◽

Abdollah Allahverdi ◽

...

Keyword(s):

Virtual Screening ◽

Angiotensin Converting Enzyme ◽

Host Cells ◽

Spike Protein ◽

Potential Drug ◽

Converting Enzyme ◽

Angiotensin Converting Enzyme 2 ◽

Approved Drugs ◽

Fda Approved Drugs

Objective: The receptor-binding domain (RBD) of the S1 domain of the SARS-CoV- 2 Spike protein performs a key role in the interaction with Angiotensin-converting enzyme 2 (ACE2), leading to both subsequent S2 domain-mediated membrane fusion and incorporation of viral RNA in host cells. Methods: In this study, we investigated the inhibitor’s targeted compounds through existing human ACE2 drugs to use as a future viral invasion. 54 FDA approved drugs were selected to assess their binding affinity to the ACE2 receptor. The structurebased methods via computational ones have been used for virtual screening of the best drugs from the drug database. Key Findings: The ligands “Cinacalcet” and “Levomefolic acid” highaffinity scores can be a potential drug preventing Spike protein of SARS-CoV-2 and human ACE2 interaction. Levomefolic acid from vitamin B family was proved to be a potential drug as a spike protein inhibitor in previous clinical and computational studies. Besides that, in this study, the capability of Levomefolic acid to avoid ACE2 and Spike protein of SARS-CoV-2 interaction is indicated. Therefore, it is worth to consider this drug for more in vitro investigations as ACE2 and Spike protein inhibition candidate. Conclusion: The two Cinacalcet and Levomefolic acid are the two ligands that have highest energy binding for human ACE2 blocking among 54 FDA approved drugs.

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