Interpretations on the Interaction between Protein Tyrosine Phosphatase and E7 Oncoproteins of High and Low-Risk HPV: A Computational Perception

Aarthy, Murali

doi:10.1021/acsomega.1c01619

Cited by 9 publications

(5 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An IFD score those accounts for both the protein‐ligand interaction and total energy of the system were calculated which is further used to rank the IFD poses. Hence, the IFD protocol has been performed for the best data set compounds of the library with better docking scores and has emerged to be the common inhibitors for both virus 26,29 …”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Drug repurposing toward the inhibition of RNA‐dependent RNA polymerase of various flaviviruses through computational study

Aarthy

Kumar

Akshaya³

2022

J of Cellular Biochemistry

Self Cite

View full text Add to dashboard Cite

Numerous pathogens affecting human is present in the f lavivirus family namely west nile, dengue, yellow fever, and zika which involves in development of global burden and distressing the environment economically. Till date, no approved drugs are available for targeting these viruses. The threat which urged the identification of small molecules for the inhibition of these viruses is the spreading of serious viral diseases. The recent outbreak of zika and dengue infections postured a solemn risk to worldwide public wellbeing. RNA-dependent RNA polymerase (RdRp) is the supreme adaptable enzymes of all the RNA viruses which is responsible for the replication and transcription of genome among the structural and nonstructural proteins of f laviviruses. It is understood that the RdRp of the f laviviruses are similar stating that the japanese encephalitis and west nile shares 70% identity with zika whereas the dengue serotype 2 and 3 shares the identity of 76% and 81%, respectively. In this study, we investigated the binding site of four flaviviral RdRp and provided insights into various interaction of the molecules using the computational approach. Our study helps in recognizing the potent compounds that could inhibit the viral protein as a common inhibitor. Additionally, with the conformational stability analysis, we proposed the possible mechanism of inhibition of the identified common small molecule toward RdRp of f lavivirus. Finally, this study could be an initiative for the identification of common inhibitors and can be explored further for understanding the mechanism of action through in vitro studies for the study on efficacy.

show abstract

Section: Methodsmentioning

confidence: 99%

“…Hence, the IFD protocol has been performed for the best data set compounds of the library with better docking scores and has emerged to be the common inhibitors for both virus. 26,29…”

Section: Induced Fit Dockingmentioning

confidence: 99%

Drug repurposing toward the inhibition of RNA‐dependent RNA polymerase of various flaviviruses through computational study

Aarthy

Kumar

Akshaya³

2022

J of Cellular Biochemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…E6 also contributes to the downregulation of the immune response against HPV by suppressing IFR3 (Interferon Regulatory Factor 3), a transcription factor for interferons (IFNs) ( 132 , 133 ), and by inhibiting IFNA (interferon alpha) interaction with its receptor ( 134 ). E7 acts synergically by inhibiting TLR9/CD289 (Toll-like receptor-9), present intracellularly in several immune cell types ( 135 , 136 ).…”

Section: Hpv Viral Components and Molecular Genetic And Epigenetic Me...mentioning

confidence: 99%

Implications of oral dysbiosis and HPV infection in head and neck cancer: from molecular and cellular mechanisms to early diagnosis and therapy

Constantin,

Chifiriuc,

Mihaescu

et al. 2023

Front. Oncol.

View full text Add to dashboard Cite

Head and neck cancer (HNC) is the sixth most common type of cancer, with more than half a million new cases annually. This review focuses on the role of oral dysbiosis and HPV infection in HNCs, presenting the involved taxons, molecular effectors and pathways, as well as the HPV-associated particularities of genetic and epigenetic changes and of the tumor microenvironment occurred in different stages of tumor development. Oral dysbiosis is associated with the evolution of HNCs, through multiple mechanisms such as inflammation, genotoxins release, modulation of the innate and acquired immune response, carcinogens and anticarcinogens production, generation of oxidative stress, induction of mutations. Thus, novel microbiome-derived biomarkers and interventions could significantly contribute to achieving the desideratum of personalized management of oncologic patients, regarding both early diagnosis and treatment. The results reported by different studies are not always congruent regarding the variations in the abundance of different taxons in HNCs. However, there is a consistent reporting of a higher abundance of Gram-negative species such as Fusobacterium, Leptotrichia, Treponema, Porphyromonas gingivalis, Prevotella, Bacteroidetes, Haemophilus, Veillonella, Pseudomonas, Enterobacterales, which are probably responsible of chronic inflammation and modulation of tumor microenvironment. Candida albicans is the dominant fungi found in oral carcinoma being also associated with shorter survival rate. Specific microbial signatures (e.g., F. nucleatum, Bacteroidetes and Peptostreptococcus) have been associated with later stages and larger tumor, suggesting their potential to be used as biomarkers for tumor stratification and prognosis. On the other hand, increased abundance of Corynebacterium, Kingella, Abiotrophia is associated with a reduced risk of HNC. Microbiome could also provide biomarkers for differentiating between oropharyngeal and hypopharyngeal cancers as well as between HPV-positive and HPV-negative tumors. Ongoing clinical trials aim to validate non-invasive tests for microbiome-derived biomarkers detection in oral and throat cancers, especially within high-risk populations. Oro-pharyngeal dysbiosis could also impact the HNCs therapy and associated side-effects of radiotherapy, chemotherapy, and immunotherapy. HPV-positive tumors harbor fewer mutations, as well as different DNA methylation pattern and tumor microenvironment. Therefore, elucidation of the molecular mechanisms by which oral microbiota and HPV infection influence the HNC initiation and progression, screening for HPV infection and vaccination against HPV, adopting a good oral hygiene, and preventing oral dysbiosis are important tools for advancing in the battle with this public health global challenge.

show abstract

“…They identi ed small molecules and EGCG as potent inhibitors against the HPV 16 E7 oncoprotein. Furthermore, Aarthy and Singh [19] utilized a computational approach to explore the relationship between protein tyrosine phosphatase and E7 oncoproteins of high-and low-risk HPV. The ndings revealed that the LXCXE domain of HPV E7 at both high and low risk adheres to a tumor suppressor protein, and that certain compounds can interfere with the interaction between the oncoprotein and tumor suppressor at the E7-PTPN14 interface.…”

Section: Introductionmentioning

confidence: 99%

Exploration of the antiviral efficacy of thiophene derivatives targeting human papillomavirus (HPV) and prevention of cancer: A comprehensive computational approach

Odey,

Gulack,

Ogar

et al. 2024

Preprint

View full text Add to dashboard Cite

Owing to the public health concern of human papillomavirus infection, which is capable of progressing into cancer among the population today, desperation to mitigate the cause of this infection is needed; hence, in this research, we unveiled the antiviral effects of four thiophene derivatives, 2B, 2C, 2D and 2E, against human papillomavirus (HPV) via computational DFT and molecular docking approaches along with ADMET prediction. Interestingly, the compounds showed great stability according to conformational assessment, spectroscopic studies (FT-IR and UV‒Vis), NBO studies, and quantum descriptor analysis. These compounds mostly exhibit LP→ LP, σ*→ σ*, and σ*→ σ transitions, as 2B shows a dominant π*→ π* orbital transition. Their reactivity was observed in different studies; for example, the HOMO-LUMO and DOS results highlighted 2B as the most reactive, among others. The energy gaps were 3.758 eV, 3.750 eV, 3.743 eV, and 3.724 eV for 2B, 2C, 2D, and 2E, respectively. During the docking process, the compounds displayed a high binding affinity and number of amino acids after interacting with the 1R8H and 4GIZ proteins of HPV, especially when they interacted with the 4GIZ protein, as the 2E-4GIZ complex displayed a robust affinity of -6.4 kcal/mol. Hence, these compounds show great antiviral potential against HPV and are promising candidates for novel HPV infection therapies.

show abstract

Interpretations on the Interaction between Protein Tyrosine Phosphatase and E7 Oncoproteins of High and Low-Risk HPV: A Computational Perception

Cited by 9 publications

References 60 publications

Drug repurposing toward the inhibition of RNA‐dependent RNA polymerase of various flaviviruses through computational study

Drug repurposing toward the inhibition of RNA‐dependent RNA polymerase of various flaviviruses through computational study

Implications of oral dysbiosis and HPV infection in head and neck cancer: from molecular and cellular mechanisms to early diagnosis and therapy

Exploration of the antiviral efficacy of thiophene derivatives targeting human papillomavirus (HPV) and prevention of cancer: A comprehensive computational approach

Contact Info

Product

Resources

About