Repurposing Therapeutics for the Wuhan Coronavirus nCov-2019: Supercomputer-Based Docking to the Viral S Protein and Human ACE2 Interface

Smith, Micholas Dean; Smith, Jeremy C.

doi:10.26434/chemrxiv.11871402.v1

Cited by 6 publications

(5 citation statements)

References 29 publications

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“…In a study by Smith et al (2020) , SUMMIT, the world’s most powerful supercomputer, was applied for the identification of approved drugs that could bind to either the S-protein receptor recognition region or the S protein-human ACE2 interface. Additionally, in this study, an ensemble virtual high-throughput screening docking strategy in combination with restrained temperature replica-exchange molecular dynamic (restrained T-REMD) simulations was used.…”

Section: Targets For Novel Drug Developmentmentioning

confidence: 99%

Structures of the SARS-CoV-2 spike glycoprotein and applications for novel drug development

et al. 2022

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COVID-19 caused by SARS-CoV-2 has raised a health crisis worldwide. The high morbidity and mortality associated with COVID-19 and the lack of effective drugs or vaccines for SARS-CoV-2 emphasize the urgent need for standard treatment and prophylaxis of COVID-19. The receptor-binding domain (RBD) of the glycosylated spike protein (S protein) is capable of binding to human angiotensin-converting enzyme 2 (hACE2) and initiating membrane fusion and virus entry. Hence, it is rational to inhibit the RBD activity of the S protein by blocking the RBD interaction with hACE2, which makes the glycosylated S protein a potential target for designing and developing antiviral agents. In this study, the molecular features of the S protein of SARS-CoV-2 are highlighted, such as the structures, functions, and interactions of the S protein and ACE2. Additionally, computational tools developed for the treatment of COVID-19 are provided, for example, algorithms, databases, and relevant programs. Finally, recent advances in the novel development of antivirals against the S protein are summarized, including screening of natural products, drug repurposing and rational design. This study is expected to provide novel insights for the efficient discovery of promising drug candidates against the S protein and contribute to the development of broad-spectrum anti-coronavirus drugs to fight against SARS-CoV-2.

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Section: Targets For Novel Drug Developmentmentioning

confidence: 99%

Structures of the SARS-CoV-2 spike glycoprotein and applications for novel drug development

et al. 2022

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“…Pemirolast is as an anti-allergic drug and has also been studied for the treatment of asthma (Fujitaka et al 1999). Pemirolast has emerged as a potential candidate for spike protein disruption and interaction with SARS-CoV-2, so it could potentially disrupt the SARS-CoV-2 interface with ACE2 receptors (Smith and Smith 2020). Hence, we analyzed the drug's binding affinity with non-mutant and mutant SARS-CoV-2 spike protein structures (Fig.…”

Section: Pemirolastmentioning

confidence: 99%

“…Another candidate drug is an antibiotic used for the treatment of tuberculosis called Isoniazid pyruvate and has been introduced to combat against SARS-CoV-2 (Smith and Smith 2020). Docking results for mutant and non-mutant structures (Fig.…”

Section: Isoniazid Pyruvatementioning

confidence: 99%

“…Nitrofurantoin or Macrobid an antibiotic used in bladder infections treatment suggested that this small molecule could mitigate SARS-CoV-2 infection (Smith and Smith 2020). In this study, top-scoring ligands for RBD-ACE2 receptor interface are contributed to A829T-, D614g-, H49y-, S247r-, L5f-, V483a-, Y28n-, P1263L-, D839n-, A879t-, R21k-, and V320g-mutated structures with the lower energies compared to the naive spike protein with docking score of − 7.7 kcal/mol (Figs.…”

Section: Nitrofurantoinmentioning

confidence: 99%

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Using In Silico Bioinformatics Algorithms for the Accurate Prediction of the Impact of Spike Protein Mutations on the Pathogenicity, Stability, and Functionality of the SARS-CoV-2 Virus and Analysis of Potential Therapeutic Targets

et al. 2022

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Coronavirus disease 2019 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We have used bioinformatics to investigate seventeen mutations in the spike protein of SARS-CoV-2, as this mediates infection of human cells and is the target of most vaccine strategies and antibody-based therapies. Two mutations, H146Y and S221W, were identified as being most pathogenic. Mutations at positions D614G, A829T, and P1263L might also have deleterious effects on protein function. We hypothesized that candidate small molecules may be repurposed to combat viral infection. We investigated changes in binding energies of the ligands and the mutant proteins by assessing molecular docking. For an understanding of cellular function and organization, protein-protein interactions are also critical. Protein-protein docking for naïve and mutated structures of SARS-CoV-2 S protein was evaluated for their binding energy with the angiotensin-converting enzyme 2 (ACE2). These interactions might limit the binding of the SARS-CoV-2 spike protein to the ACE2 receptor or may have a deleterious effect on protein function that may limit infection. These results may have important implications for the transmission of SARS-CoV-2, its pathogenesis, and the potential for drug repurposing and immune therapies.

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“…In another study, a machine learning model has predicted the antibody response for COVID-19 via a screening of 1933 virus antibody sequences collected from a dataset, and contains antibody-antigen sequences of various viruses such as SARS, Ebola and Influenza with the IC 50 values of neutralization panel, the inhibitory effect of 8 mutant stable antibodies has been noticed against COVID-19 at a class prediction of 100% showing that a mutation in amino acids (from Methionine to Tyrosine) is beneficial and increases the antibodies affinity against COVID-19 [98]. In the same vein of virtual prediction and repurposing methods, a wide range of investigations have been reported, using different statistical modeling of drugs and compounds from various libraries such as medicinal plants [99], FDA-approved drugs [100], antivirals drugs [101] against different targets including nucleotide inhibitors [102], protease and RNA polymerase [103], viral spike protein [104].…”

Section: Recent Advances In Therapeutic Alternatives Against Sars-cov-2: Virtual Screening Neutralizing Antibodies and Othersmentioning

confidence: 99%

From Wuhan to COVID-19 Pandemic: An Up-to-Date Review of Its Pathogenesis, Potential Therapeutics, and Recent Advances

2020

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The emergence of a novel human coronavirus (SARS-CoV-2) causing severe contagious respiratory tract infections presents a serious threat to public health worldwide. To date, there are no specific antiviral agents available for this disease, currently known as COVID-19. Therefore, genomic sequencing and therapeutic clinical trials are being conducted to develop effective antiviral agents. Several reports have investigated FDA-approved drugs as well as in silico virtual screening approaches such as molecular docking and modeling to find novel antiviral agents. Until now, antiparasitic drugs such as chloroquine have shown the most relevant results. Furthermore, there is an urgent need to understand the pathogenesis of this novel coronavirus, its transmission routes, surface survival and evolution in the environment. So far, the scientific community has indicated a possible transmission of COVID-19 via blood transfusion which is challenging in the case of asymptomatic individuals. Protocols for pathogen inactivation are also needed. In this paper, we reviewed recent findings about this life-threatening pandemic.

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Repurposing Therapeutics for the Wuhan Coronavirus nCov-2019: Supercomputer-Based Docking to the Viral S Protein and Human ACE2 Interface

Cited by 6 publications

References 29 publications

Structures of the SARS-CoV-2 spike glycoprotein and applications for novel drug development

Structures of the SARS-CoV-2 spike glycoprotein and applications for novel drug development

Using In Silico Bioinformatics Algorithms for the Accurate Prediction of the Impact of Spike Protein Mutations on the Pathogenicity, Stability, and Functionality of the SARS-CoV-2 Virus and Analysis of Potential Therapeutic Targets

From Wuhan to COVID-19 Pandemic: An Up-to-Date Review of Its Pathogenesis, Potential Therapeutics, and Recent Advances

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