Computational and theoretical exploration for clinical suitability of Remdesivir drug to SARS-CoV-2

Nayeem, Shaik Mahammad; Sohail, Dr. Ershad Mohammed; Sudhir, Gajjela Priyanka; Reddy, M. Srinivasa

doi:10.1016/j.ejphar.2020.173642

Cited by 8 publications

(4 citation statements)

References 54 publications

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“…According to Moradi, destruction (Moradi et al, 2018) of SARS-CoV-2 main protease with the binding of Favipiravir (ligand) drug will happen due to positive entropy. Similar conclusion was arrived from the dominance of electrostatic interaction over other types between SARS-CoV-2 main protease and the drug Remdesivir with OPLS-AA force field (Nayeem et al, 2021). Thus, the result of thermodynamic entropy also supports the conclusions arrived from RMSD/ Rg/RMSF and observed interaction energies of Table 2.…”

Section: Exploration On Thermodynamical Potentialssupporting

confidence: 82%

Target SARS-CoV-2: theoretical exploration on clinical suitability of certain drugs

Nayeem¹,

Sohail

Indira³

et al. 2021

Journal of Biomolecular Structure and Dynamics

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We propose a unique theoretical methodology because of the global high priority rating to search for the repurposed drugs that outfit clinical suitability to SARS-CoV-2. The approach is based on the exploration of structural analysis, computation of biothermodynamics, interactions and the prediction of entropy sign successively via molecular dynamics. We tested this methodology for Favipiravir/Dolutegravir drugs on the apo form of SARS-CoV-2 main protease. This theoretical exploration not only suggested the presence of strong interactions between (SARS-CoV-2 + Favipiravir/Dolutegravir) but also emphasized the clinical suitability of Favipiravir over Dolutegravir to treat SARS-CoV-2 main protease. The supremacy of Favipiravir over Doultegravir is well supported by the results of global clinical trials on SARS-CoV-2 infection. Thus, this work will pave the way for incremental advancement towards future design and development of more specific inhibitors to treat SARS-CoV-2 infection in humans. Communicated by Ramaswamy H. Sarma

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Section: Exploration On Thermodynamical Potentialssupporting

confidence: 82%

Target SARS-CoV-2: theoretical exploration on clinical suitability of certain drugs

Nayeem¹,

Sohail

Indira³

et al. 2021

Journal of Biomolecular Structure and Dynamics

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“…MD simulation was accomplished with GROMACS v2021 (CUDA compiled) on Linux operating system (Ubuntu v20.04 LTS) 27 to study the behavior of hACE2‐S477N complex over time and the effect of this displacement on the structural properties of the spike using Newtonian equations. Pressure, temperature, and neutralizing conditions for the equilibrium of systems were checked before starting the MD analysis.…”

Section: Methodsmentioning

confidence: 99%

The role of S477N mutation in the molecular behavior of SARS‐CoV‐2 spike protein: An in‐silico perspective

Mondeali

Etemadi

Barkhordari

et al. 2023

J of Cellular Biochemistry

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The attachment of SARA-CoV-2 happens between ACE2 and the receptor binding domain (RBD) on the spike protein. Mutations in this domain can affect the binding affinity of the spike protein for ACE2. S477N, one of the most common mutations reported in the recent variants, is located in the RBD.Today's computational approaches in biology, especially during the SARS-CoV-2 pandemic, assist researchers in predicting a protein's behavior in contact with other proteins in more detail. In this study, we investigated the interactions of the S477N-hACE2 in silico to find the impact of this mutation on its binding affinity for ACE2 and immunity responses using dynamics simulation, protein-protein docking, and immunoinformatics methods. Our computational analysis revealed an increased binding affinity of N477 for ACE2. Four new hydrogen and hydrophobic bonds in the mutant RBD-ACE2 were formed (with S19 and Q24 of ACE2), which do not exist in the wild type. Also, the protein spike structure in this mutation was associated with an increase in stabilization and a decrease in its fluctuations at the atomic level. N477 mutation can be considered as the cause of increased escape from the immune system through MHC-II.

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“…Remdesivir, an inhibitor of the viral RNA-dependent RNA polymerase, was used as COVID-19 therapeutic. Interestingly, it is also able to interact with SARS−CoV−2 M pro [ 73 ].…”

Section: Erms and Estrogens As Inhibitors Of Sars−cov−2 Proteasesmentioning

confidence: 99%

Estrogen Receptor Modulators in Viral Infections Such as SARS−CoV−2: Therapeutic Consequences

Abramenko

Vellieux

Tesařová

et al. 2021

IJMS

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COVID−19 is a pandemic respiratory disease caused by the SARS−CoV−2 coronavirus. The worldwide epidemiologic data showed higher mortality in males compared to females, suggesting a hypothesis about the protective effect of estrogens against severe disease progression with the ultimate end being patient’s death. This article summarizes the current knowledge regarding the potential effect of estrogens and other modulators of estrogen receptors on COVID−19. While estrogen receptor activation shows complex effects on the patient’s organism, such as an influence on the cardiovascular/pulmonary/immune system which includes lower production of cytokines responsible for the cytokine storm, the receptor-independent effects directly inhibits viral replication. Furthermore, it inhibits the interaction of IL−6 with its receptor complex. Interestingly, in addition to natural hormones, phytestrogens and even synthetic molecules are able to interact with the estrogen receptor and exhibit some anti-COVID−19 activity. From this point of view, estrogen receptor modulators have the potential to be included in the anti-COVID−19 therapeutic arsenal.

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Computational and theoretical exploration for clinical suitability of Remdesivir drug to SARS-CoV-2

Cited by 8 publications

References 54 publications

Target SARS-CoV-2: theoretical exploration on clinical suitability of certain drugs

Target SARS-CoV-2: theoretical exploration on clinical suitability of certain drugs

The role of S477N mutation in the molecular behavior of SARS‐CoV‐2 spike protein: An in‐silico perspective

Estrogen Receptor Modulators in Viral Infections Such as SARS−CoV−2: Therapeutic Consequences

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