Pharmaceutical chemistry

Abelian, Anush; Dybek, Michael; Wallach, Jason; Gaye, Boyenoh; Adejare, Adeboye

doi:10.1016/b978-0-12-820007-0.00006-4

Cited by 24 publications

(20 citation statements)

References 12 publications

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“…The conserved H-bond Lys353-Gly496 was found only in BA.2 and Delta, but not in BA.1. H-bonds are critical in drug–receptor interactions because they help maintain the biomolecules’ structural integrity and three-dimensional conformation [ 51 , 52 ]. H-bonds also play a significant role in protein–protein interactions, owing to their stronger bonds than van der Waals interactions, despite their weakness in comparison to covalent or ionic bonds [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

An Insight Based on Computational Analysis of the Interaction between the Receptor-Binding Domain of the Omicron Variants and Human Angiotensin-Converting Enzyme 2

Çeli̇k

Abdellattif

Tallei

2022

Biology

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Concerns have been raised about the high number of mutations in the spike protein of the new emergence of the highly transmissible Omicron variant (B.1.1529 lineage) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This variant’s extraordinary ability to evade antibodies would significantly impair the current vaccination program. This present study aimed to computationally analyze the interaction between the receptor-binding domain (RBD) in the spike protein of Omicron variants and human angiotensin-converting enzyme 2 (hACE2). The docking results indicated that Omicron BA.2 has exceptionally strong interactions with hACE2 in comparison to Omicron BA.1, Delta, and wild-type, as indicated by various parameters such as salt bridge, hydrogen bond, and non-bonded interactions. The results of the molecular dynamics simulation study corroborate these findings, indicating that Omicron BA.2 has a strong and stable interaction with hACE2. This study provides insight into the development of an effective intervention against this variant.

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Section: Discussionmentioning

confidence: 99%

An Insight Based on Computational Analysis of the Interaction between the Receptor-Binding Domain of the Omicron Variants and Human Angiotensin-Converting Enzyme 2

Çeli̇k

Abdellattif

Tallei

2022

Biology

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“…Hydrogen bonds (H-bonds) are shown as green dotted lines. H-bonds play a critical role in drug-receptor interactions and in the structural integrity of a large number of biological molecules [ 64 ]. In addition to the van der Waals interaction in a complex, intermolecular hydrogen bonds contribute to the scoring function used to assess docking effectiveness [ 65 ].…”

Section: Resultsmentioning

confidence: 99%

Fruit Bromelain-Derived Peptide Potentially Restrains the Attachment of SARS-CoV-2 Variants to hACE2: A Pharmacoinformatics Approach

et al. 2022

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Before entering the cell, the SARS-CoV-2 spike glycoprotein receptor-binding domain (RBD) binds to the human angiotensin-converting enzyme 2 (hACE2) receptor. Hence, this RBD is a critical target for the development of antiviral agents. Recent studies have discovered that SARS-CoV-2 variants with mutations in the RBD have spread globally. The purpose of this in silico study was to determine the potential of a fruit bromelain-derived peptide. DYGAVNEVK. to inhibit the entry of various SARS-CoV-2 variants into human cells by targeting the hACE binding site within the RBD. Molecular docking analysis revealed that DYGAVNEVK interacts with several critical RBD binding residues responsible for the adhesion of the RBD to hACE2. Moreover, 100 ns MD simulations revealed stable interactions between DYGAVNEVK and RBD variants derived from the trajectory of root-mean-square deviation (RMSD), radius of gyration (Rg), and root-mean-square fluctuation (RMSF) analysis, as well as free binding energy calculations. Overall, our computational results indicate that DYGAVNEVK warrants further investigation as a candidate for preventing SARS-CoV-2 due to its interaction with the RBD of SARS-CoV-2 variants.

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“…This drug has more H‐bonds with D‐AY.4 RdRP than with WT RdRP. H‐bonds play a critical role in drug‐receptor interactions and the structural integrity of a large number of biological molecules 44 . They have been identified as being responsible for the conformation and three‐dimensional structure of biomolecules 45 .…”

Section: Discussionmentioning

confidence: 99%

“…H-bonds play a critical role in drugreceptor interactions and the structural integrity of a large number of biological molecules. 44 They have been…”

Section: Discussionmentioning

confidence: 99%

A computational comparative analysis of the binding mechanism of molnupiravir's active metabolite to RNA‐dependent RNA polymerase of wild‐type and Delta subvariant AY.4 of SARS‐CoV‐2

Çeli̇k

Tallei

2022

J of Cellular Biochemistry

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The antiviral drug molnupiravir targets the SARS‐CoV‐2 RNA‐dependent RNA polymerase (RdRP) enzyme. Early treatment with molnupiravir reduced the risk of hospitalization or death in at‐risk, unvaccinated adults with COVID‐19, according to phase 3 clinical trials. Many mutations have occurred within this virus as a result of its widespread distribution. The current study sought to determine whether mutations in the RdRP of Delta subvariant AY.4 (D‐AY.4 RdRP) influence the interaction of the enzyme with molnupiravir triphosphate (MTP), the active metabolite of molnupiravir. The interactions between the wild‐type (WT) RdRP and D‐AY.4 RdRP with MTP were evaluated based on molecular docking and dynamic simulation (MD) studies. The results show that the MTP interaction is stronger and more stable with D‐AY.4 RdRP than with WT RdRP. This study provides insight into the potential significance of administering MTP to patients infected with D‐AY.4 RdRP, which may have a more favorable chance of alleviating the illness. According to the findings of this study, MTP has a high likelihood of becoming widely used as an anti‐SARS‐CoV‐2 agent. The fact that MTP is not only cytotoxic but also mutagenic to mammalian cells, as well as the possibility that it may cause DNA damage in the host, have all been raised as potential concerns.

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Pharmaceutical chemistry

Cited by 24 publications

References 12 publications

An Insight Based on Computational Analysis of the Interaction between the Receptor-Binding Domain of the Omicron Variants and Human Angiotensin-Converting Enzyme 2

An Insight Based on Computational Analysis of the Interaction between the Receptor-Binding Domain of the Omicron Variants and Human Angiotensin-Converting Enzyme 2

Fruit Bromelain-Derived Peptide Potentially Restrains the Attachment of SARS-CoV-2 Variants to hACE2: A Pharmacoinformatics Approach

A computational comparative analysis of the binding mechanism of molnupiravir's active metabolite to RNA‐dependent RNA polymerase of wild‐type and Delta subvariant AY.4 of SARS‐CoV‐2

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