Targeting the PI3K/AKT pathway: a potential new weapon in the global fight against SARS-CoV-2?

Santamaria, Salvatore

doi:10.7150/ijbs.63969

Cited by 6 publications

(3 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, we reported that PI3K/AKT signal pathway is essential in COVID-19 and capivasertib as an inhibitor restricts SARS-CoV-2 entry into host cells [ 31 , 32 ]. In addition, based on our hypothesis mentioned above, to further investigate the potential of combination therapy by EGFR and AKT inhibitors would be promising in anti-variants.…”

Section: Resultsmentioning

confidence: 99%

Omicron N501Y mutation among SARS-CoV-2 lineages: In silico analysis of potent binding to tyrosine kinase and hypothetical repurposed medicine

Kazybay

Ahmad

et al. 2022

Travel Medicine and Infectious Disease

View full text Add to dashboard Cite

Variants of SARS-CoV-2 lineages including the most recently circulated Omicron, and previous pandemic B.1.351, B.1.1.7, which have been public concerns, contain a N501Y mutation located in the spike receptor binding domain. However, the potential interactions with host cells linking N501Y mutation to pathogenic relevance remain elusive. Recently, we and others report that kinases such as PI3K/AKT signaling is essential in SARS-CoV-2 entry. Here we analyzed the predicted potential kinases interacting with the mutation. Bioinformatics tools including structure-prediction based molecular docking analysis were applied. We found kinases such as EGFR might potentially act as new acceptors involving the N501Y mutation binding through possible phosphorylation at Y501 and enhanced affinity in certain variants. To our surprise, the Omicron receptor binding domain harboring N501Y mutation did not enhance binding to EGFR which might be due to the mutations of charged polar to uncharged polar side chains located on the interaction interfaces. Similarly, potent gains of phosphorylation in B.1.351 and B.1.1.7 by mutations were predicted and interaction networks were analyzed with enrichment of pathways. Given kinases might be elevated in cancer patients, the N501Y mutation containing lineages may be possibly much more infectious and additional care for cancer management might be taken into consideration by precision prevention, therapy or recovery.

show abstract

Section: Resultsmentioning

confidence: 99%

Omicron N501Y mutation among SARS-CoV-2 lineages: In silico analysis of potent binding to tyrosine kinase and hypothetical repurposed medicine

Kazybay

Ahmad

et al. 2022

Travel Medicine and Infectious Disease

View full text Add to dashboard Cite

show abstract

“…They suggested that targeting the identi ed kinase-network of COVID-19 and AKT may be a unique treatment strategy for patients with COVID-19 and cancer [39]. AKT1 has also been an interesting therapeutic target for COVID-19 diseases [40][41][42][43][44]. Considering this association and absence of any previous docking studies between individual SARS-CoV-2 proteins and AKT1 molecules, we performed protein-protein docking to analyze their interaction.…”

Section: Discussionmentioning

confidence: 99%

Predictive etiology of Long COVID oncogenesis through SARS-CoV-2 proteins and AKT1 molecular docking interactions

Nawaz,

Qazi,

Ahad

et al. 2023

Preprint

View full text Add to dashboard Cite

Background: In 2019, the world witnessed an outbreak of SARS-CoV-2, whose retention for two months or more leads to long COVID. Several long-term staying viruses cause oncogenesis. We intended to find any such potential with SARS-CoV-2. A rigorous systematic analysis of viral oncogenic pathways and long COVID was conducted. SARS-CoV-2 affects glutamatergic and Protein Tyrosine Kinases 1 signalling, leading to molecular interference. AKT1 protein was analyzed for predictive interaction studies with structural and non-structural viral proteins. Molecular docking simulations were also carried out. Methods:Oncogenes were detected in SARS-CoV-2 protein sequence, using TAG database. AKT1 was selected as a high potential oncogenic factor and was modelled using SWISS-MODEL. Viral proteins structures were either downloaded from Protein Data Bank, otherwise modelled. Docking was performed using HDOCK server. Prediction of possible potential active sites was done using Protein Allosteric and Regulatory Site (PARS). Results: AKT1 showed very strong interactive potential with all viral proteins with docking scores less than -200, envelope protein being the most potently reactive. PARS analysis showed that there might be more than one potential active site. All proteins cavities satisfied the requirement for flexibility p-value. NSP5 showed great structural conservation. Conclusion: When SARS-CoV-2 stays in the body of infected person for extended time durations, it has a strong oncogenic potential. Given the host of cellular targets because of angiotensin-converting enzyme type-2 presence, any infected organ harboring the virus for longer terms might be at risk of developing cancer. We propose further molecular and case study investigations to assess this threat to full extent.

show abstract

“…There are a lot of antitumor drugs that target the PI3K/AKT signaling pathway. This might be used in treating critical COVID19 cancer patients in the era of the pandemic [89][90][91].…”

Section: Pi3k and Sars-cov-2mentioning

confidence: 99%

Possible Therapeutic Targets from Derivatives of Natural Marine Products Based on PI3K/AKT Dependent Inhibitors in Viral Infection COVID-19

Aleebrahim-Dehkordi

Koochaki

Samami

et al. 2022

Cell Physiol Biochem

View full text Add to dashboard Cite

Natural resources have long played a prominent part in conventional treatments as a parental source due to their multifaceted functions and lesser side effects. The diversity of marine products is a significant source of possible bioactive chemical compounds with a wide range of potential medicinal applications. Marine organisms produce natural compounds and new drugs with unique properties are produced from these compounds. A lot of bioactive compounds with medicinal properties are extracted from marine invertebrates, including Peptides, Alkaloids, Terpenoids, Steroids. Thus, it can be concluded that marine ecosystems are endowed with natural resources that have a wide range of medicinal properties, and it is important to examine the therapeutic and pharmacological capabilities of these molecules. So, finding particular inhibitors of the COVID-19 in natural compounds will be extremely important. Natural ingredients, in this light, could be a valuable resource in the progression of COVID-19 therapeutic options. Controlling the immunological response in COVID-19 patients may be possible by addressing the PI3K/Akt pathway and regulating T cell responses. T cell effector activity can be improved by preventing anti-viral exhaustion by suppressing PI3K and Akt during the early anti-viral response. The diversity of marine life is a significant supply of potentially bioactive chemical compounds with a broad range of medicinal uses. In this study, some biologically active compounds from marine organisms capable of inhibiting PI3K/AKT and the possible therapeutic targets from these compounds in viral infection COVID-19 have been addressed.

show abstract

Targeting the PI3K/AKT pathway: a potential new weapon in the global fight against SARS-CoV-2?

Abstract: Commentary on 'Capivasertib restricts SARS-CoV-2 cellular entry: a potential clinical application for COVID-19' by Sun et al.

Cited by 6 publications

References 10 publications

Omicron N501Y mutation among SARS-CoV-2 lineages: In silico analysis of potent binding to tyrosine kinase and hypothetical repurposed medicine

Omicron N501Y mutation among SARS-CoV-2 lineages: In silico analysis of potent binding to tyrosine kinase and hypothetical repurposed medicine

Predictive etiology of Long COVID oncogenesis through SARS-CoV-2 proteins and AKT1 molecular docking interactions

Possible Therapeutic Targets from Derivatives of Natural Marine Products Based on PI3K/AKT Dependent Inhibitors in Viral Infection COVID-19

Contact Info

Product

Resources

About