Pathway enrichment analysis of virus-host interactome and prioritization of novel compounds targeting the spike glycoprotein receptor binding domain–human angiotensin-converting enzyme 2 interface to combat SARS-CoV-2

Gollapalli, Pavan; Sharath, B S; Rimac, Hrvoje; Patil, Prakash; Nalilu, Suchetha Kumari; Kandagalla, Shivanandha; Shetty, Praveenkumar

doi:10.1080/07391102.2020.1841681

Cited by 8 publications

(5 citation statements)

References 56 publications

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“…The biological response of small molecules in a living organisms is largely regulated by their interaction partners (Sharan et al, 2007 ). The role of the interaction network becomes more important in computer aided drug design (CADD), since diseases are often reflected by alterations of protein complex of the certain pathways (Gollapalli et al, 2020 ; Oti et al, 2006 ). The cordycepin-protein network data revealed that cordycepin can modulate multiple pathways associated with apoptosis, cancer, hepatitis B, tuberculosis, influenza A, herpes simplex infection and many more.…”

Section: Resultsmentioning

confidence: 99%

Cordycepin: a bioactive metabolite of C ordyceps militaris and polyadenylation inhibitor with therapeutic potential against COVID-19

Verma

2020

Journal of Biomolecular Structure and Dynamics

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Spike protein and main proteases of SARS-CoV-2 have been identified as potential therapeutic targets and their inhibition may lead to the reticence of viral entry and replication in the host body. Despite several efforts; till now no specific drugs are available to treat SARS-CoV-2. Considering all these challenges, the main objective of the present study was to establish therapeutic potential of cordycepin against COVID-19 as a conventional therapeutic strategy. In the present study; molecular interaction study was performed to assess potential binding affinity of cordycepin with SARS-CoV-2 target proteins using computational approach. Additionally, network pharmacology was used to understand cordycepin-protein interactions and their associated pathways in human body. Cordycepin is under clinical trial (NCT00709215) and possesses structural similarity with adenosine except that, it lacks a 3 0 hydroxyl group in its ribose moiety and hence it served as a poly(A) polymerase inhibitor and terminate premature protein synthesis. Additionally, it is known that functional RNAs of SARS-CoV-2 genome are highly 3'-plyadenylated and leading to synthesis of all viral proteins and if cordycepin can destabilize SARS-CoV-2 RNAs by inhibiting polyadenylation process then it may step forward in terms of inhibition of viral replication and multiplication in the host. Moreover, cordycepin showed strong binding affinity with SARS-CoV-2 spike protein (-145.3) and main proteases (-180.5) that further corroborate therapeutic potential against COVID-19. Since cordycepin has both pre-clinical and clinical information about antiviral activities, therefore; it is suggested to the world community to undertake repurposing cordycepin to test efficacy and safety for the treatment of COVID-19.

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Section: Resultsmentioning

confidence: 99%

Cordycepin: a bioactive metabolite of C ordyceps militaris and polyadenylation inhibitor with therapeutic potential against COVID-19

Verma

2020

Journal of Biomolecular Structure and Dynamics

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“…Recently, there has been some evidence indicating that quercetin exhibits anti‐coronavirus properties, mostly through its anti‐inflammatory effects (Valério et al, 2009 ). To enter human cells, the COVID‐19 virus, being an RNA‐based virus, recruits the angiotensin‐converting enzyme 2 receptors (hACE‐2) (Gollapalli et al, 2022 ). The COVID‐19 virus uses hACE‐2 to initiate cascades that lead to high levels of proinflammatory cytokines, reactive oxygen species, and eventually acute respiratory distress syndrome (Kuppusamy et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

The effect of quercetin supplementation on clinical outcomes in COVID‐19 patients: A systematic review and meta‐analysis

Ziaei,

Alimohammadi‐Kamalabadi,

Hasani

et al. 2023

Food Science & Nutrition

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Coronavirus disease (COVID‐19) affects both the respiratory system and the body as a whole. Natural molecules, such as flavonoid quercetin, as potential treatment methods to help patients combat COVID‐19. The aim of this systematic review and meta‐analysis is to give a comprehensive overview of the impact of quercetin supplementation on inflammatory factors, hospital admission, and mortality of patients with COVID‐19. The search has been conducted on PubMed, Scopus, Web of Science, EMBASE, and the Cochrane Library using relevant keywords until August 25, 2023. We included randomized controlled trials (RCTs) comparing COVID‐19 patients who received quercetin supplementation versus controls. We included five studies summarizing the evidence in 544 patients. Meta‐analysis showed that quercetin administration significantly reduced LDH activity (standard mean difference (SMD): −0.42, 95% CI: −0.82, −0.02, I2 = 48.86%), decreased the risk of hospital admission by 70% (RR: 0.30, 95% CI: 0.14, 0.62, I2 = 00.00%), ICU admission by 73% (RR: 0.27, 95% CI: 0.09, 0.78, I2 = 20.66%), and mortality by 82% (RR: 0.18, 95% CI: 0.03, 0.98, I2 = 00.00%). No significant changes in CRP, D‐dimmer, and ferritin were found between groups. Quercetin was found to significantly reduce LDH levels and decrease the risk of hospital and ICU admission and mortality in patients with COVID‐19 infection.

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“…The cellular component of phagocytic vesicles (GO:0045335) was also mentioned in the context of SARS-CoV-2 infection and pulmonary fibrosis [ 35 ]. Additionally, the enriched molecular function GO:0042287, responsible for MHC protein binding was found in a recent SARS-CoV-2 study [ 36 ], based on an enrichment analysis in 76 selected neighbor proteins of the SARS-CoV-2 spike protein. In the EBI QuickGO database the term GO:0042287 is further described as ‘Binding to a major histocompatibility complex molecule; a set of molecules displayed on cell surfaces that are responsible for lymphocyte recognition and antigen presentation’.…”

Section: Discussionmentioning

confidence: 99%

Augmentation of Transcriptomic Data for Improved Classification of Patients with Respiratory Diseases of Viral Origin

Kircher¹,

Chludzinski²,

Krepel³

et al. 2022

IJMS

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To better understand the molecular basis of respiratory diseases of viral origin, high-throughput gene-expression data are frequently taken by means of DNA microarray or RNA-seq technology. Such data can also be useful to classify infected individuals by molecular signatures in the form of machine-learning models with genes as predictor variables. Early diagnosis of patients by molecular signatures could also contribute to better treatments. An approach that has rarely been considered for machine-learning models in the context of transcriptomics is data augmentation. For other data types it has been shown that augmentation can improve classification accuracy and prevent overfitting. Here, we compare three strategies for data augmentation of DNA microarray and RNA-seq data from two selected studies on respiratory diseases of viral origin. The first study involves samples of patients with either viral or bacterial origin of the respiratory disease, the second study involves patients with either SARS-CoV-2 or another respiratory virus as disease origin. Specifically, we reanalyze these public datasets to study whether patient classification by transcriptomic signatures can be improved when adding artificial data for training of the machine-learning models. Our comparison reveals that augmentation of transcriptomic data can improve the classification accuracy and that fewer genes are necessary as explanatory variables in the final models. We also report genes from our signatures that overlap with signatures presented in the original publications of our example data. Due to strict selection criteria, the molecular role of these genes in the context of respiratory infectious diseases is underlined.

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Pathway enrichment analysis of virus-host interactome and prioritization of novel compounds targeting the spike glycoprotein receptor binding domain–human angiotensin-converting enzyme 2 interface to combat SARS-CoV-2

Cited by 8 publications

References 56 publications

Cordycepin: a bioactive metabolite of C ordyceps militaris and polyadenylation inhibitor with therapeutic potential against COVID-19

Cordycepin: a bioactive metabolite of C ordyceps militaris and polyadenylation inhibitor with therapeutic potential against COVID-19

The effect of quercetin supplementation on clinical outcomes in COVID‐19 patients: A systematic review and meta‐analysis

Augmentation of Transcriptomic Data for Improved Classification of Patients with Respiratory Diseases of Viral Origin

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