In Silico Screening and Testing of FDA-Approved Small Molecules to Block SARS-CoV-2 Entry to the Host Cell by Inhibiting Spike Protein Cleavage

Ozdemir, E. Sila; Le, Hillary; Yıldırım, Adem; Ranganathan, S.

doi:10.3390/v14061129

Cited by 4 publications

(1 citation statement)

References 53 publications

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“…TMPRSS2 cleavage of the spike protein is a critical step in viral entry because it allows the virus to fuse with the host cell membrane and release its genetic material [21]. Inhibiting the activity of TMPRSS2 can prevent the cleavage of the spike protein, thus preventing viral entry into host cells [21,22]. Several drugs that target TMPRSS2 have been investigated, including Camostat Mesylate, which is approved for use in Japan as a treatment for pancreatitis [23,24].…”

Section: Sars-cov-2 Receptorsmentioning

confidence: 99%

Assessing the Potential Contribution of In Silico Studies in Discovering Drug Candidates That Interact with Various SARS-CoV-2 Receptors

Mushebenge,

Ugbaja,

Mbatha

et al. 2023

IJMS

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The COVID-19 pandemic has spurred intense research efforts to identify effective treatments for SARS-CoV-2. In silico studies have emerged as a powerful tool in the drug discovery process, particularly in the search for drug candidates that interact with various SARS-CoV-2 receptors. These studies involve the use of computer simulations and computational algorithms to predict the potential interaction of drug candidates with target receptors. The primary receptors targeted by drug candidates include the RNA polymerase, main protease, spike protein, ACE2 receptor, and transmembrane protease serine 2 (TMPRSS2). In silico studies have identified several promising drug candidates, including Remdesivir, Favipiravir, Ribavirin, Ivermectin, Lopinavir/Ritonavir, and Camostat Mesylate, among others. The use of in silico studies offers several advantages, including the ability to screen a large number of drug candidates in a relatively short amount of time, thereby reducing the time and cost involved in traditional drug discovery methods. Additionally, in silico studies allow for the prediction of the binding affinity of the drug candidates to target receptors, providing insight into their potential efficacy. This study is aimed at assessing the useful contributions of the application of computational instruments in the discovery of receptors targeted in SARS-CoV-2. It further highlights some identified advantages and limitations of these studies, thereby revealing some complementary experimental validation to ensure the efficacy and safety of identified drug candidates.

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Section: Sars-cov-2 Receptorsmentioning

confidence: 99%

Assessing the Potential Contribution of In Silico Studies in Discovering Drug Candidates That Interact with Various SARS-CoV-2 Receptors

Mushebenge,

Ugbaja,

Mbatha

et al. 2023

IJMS

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Virtual screening and molecular dynamics simulations provide insight into repurposing drugs against SARS-CoV-2 variants Spike protein/ACE2 interface

Pirolli¹,

Righino²,

Camponeschi³

et al. 2023

Sci Rep

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After over two years of living with Covid-19 and hundreds of million cases worldwide there is still an unmet need to find proper treatments for the novel coronavirus, due also to the rapid mutation of its genome. In this context, a drug repositioning study has been performed, using in silico tools targeting Delta Spike protein/ACE2 interface. To this aim, it has been virtually screened a library composed by 4388 approved drugs through a deep learning-based QSAR model to identify protein–protein interactions modulators for molecular docking against Spike receptor binding domain (RBD). Binding energies of predicted complexes were calculated by Molecular Mechanics/Generalized Born Surface Area from docking and molecular dynamics simulations. Four out of the top twenty ranking compounds showed stable binding modes on Delta Spike RBD and were evaluated also for their effectiveness against Omicron. Among them an antihistaminic drug, fexofenadine, revealed very low binding energy, stable complex, and interesting interactions with Delta Spike RBD. Several antihistaminic drugs were found to exhibit direct antiviral activity against SARS-CoV-2 in vitro, and their mechanisms of action is still debated. This study not only highlights the potential of our computational methodology for a rapid screening of variant-specific drugs, but also represents a further tool for investigating properties and mechanisms of selected drugs.

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How has artificial intelligence impacted COVID-19 drug repurposing and what lessons have we learned?

Özdemir

Ranganathan

Nussinov

2022

Expert Opinion on Drug Discovery

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In Silico Screening and Testing of FDA-Approved Small Molecules to Block SARS-CoV-2 Entry to the Host Cell by Inhibiting Spike Protein Cleavage

Cited by 4 publications

References 53 publications

Assessing the Potential Contribution of In Silico Studies in Discovering Drug Candidates That Interact with Various SARS-CoV-2 Receptors

Assessing the Potential Contribution of In Silico Studies in Discovering Drug Candidates That Interact with Various SARS-CoV-2 Receptors

Virtual screening and molecular dynamics simulations provide insight into repurposing drugs against SARS-CoV-2 variants Spike protein/ACE2 interface

How has artificial intelligence impacted COVID-19 drug repurposing and what lessons have we learned?

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