The Host Cell ViroCheckpoint: Identification and Pharmacologic Targeting of Novel Mechanistic Determinants of Coronavirus-Mediated Hijacked Cell States

Laise, Pasquale; Bosker, Gideon; Sun, Xiaoyun; Shen, Yao; Douglass, Eugene F.; Karan, Charles; Realubit, Ronald; Pampou, Sergey; Califano, Andrea; Alvarez, Mariano J.

doi:10.1101/2020.05.12.091256

Cited by 17 publications

(22 citation statements)

References 79 publications

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“…Recently, Laise et al (50) identified 12h, 24h, and 48h signatures from calu-3 lung adenocarcinoma cells infected with SARS-CoV, which included genes related to cell cycle progression, viz., E2F and mTOR.…”

Section: Viruses Can Influence Host Cell Cycle In Favor Of Their Own Replicationmentioning

confidence: 99%

ROS/RNS balancing, aerobic fermentation regulation and cell cycle control – a complex early trait (‘CoV-MAC-TED’) for combating SARS-CoV-2-induced cell reprogramming

Costa

Mohanapriya

Bharadwaj

et al. 2021

Preprint

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In a perspective entitled From plant survival under severe stress to anti-viral human defense we raised and justified the hypothesis that transcript level profiles of justified target genes established from in vitro somatic embryogenesis (SE) induction in plants as a reference compared to virus-induced profiles can identify differential virus signatures that link to harmful reprogramming. A standard profile of selected genes named ReprogVirus was proposed for in vitro-scanning of early virus-induced reprogramming in critical primary infected cells/tissues as target trait. For data collection, the ReprogVirus platform was initiated. This initiative aims to identify in a common effort across scientific boundaries critical virus footprints from diverse virus origins and variants as a basis for anti-viral strategy design. This approach is open for validation and extension. In the present study, we initiated validation by experimental transcriptome data available in public domain combined with advancing plant wet lab research. We compared plant-adapted transcriptomes according to RegroVirus complemented by alternative oxidase (AOX) genes during de novo programming under SE-inducing conditions with in vitro corona virus-induced transcriptome profiles. This approach enabled identifying a major complex trait for early de novo programming during SARS-CoV-2 infection, called CoV-MAC-TED. It consists of unbalanced ROS/RNS levels, which are connected to increased aerobic fermentation that links to alpha-tubulin-based cell restructuration and progression of cell cycle. We conclude that anti-viral/anti-SARS-CoV-2 strategies need to rigorously target CoV-MAC-TED in primary infected nose and mouth cells through prophylactic and very early therapeutic strategies. We also discuss potential strategies in the view of the beneficial role of AOX for resilient behavior in plants. Furthermore, following the general observation that ROS/RNS equilibration/redox homeostasis is of utmost importance at the very beginning of viral infection, we highlight that de-stressing disease and social handling should be seen as essential part of anti-viral/anti-SARS-CoV-2 strategies.

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Section: Viruses Can Influence Host Cell Cycle In Favor Of Their Own Replicationmentioning

confidence: 99%

ROS/RNS balancing, aerobic fermentation regulation and cell cycle control – a complex early trait (‘CoV-MAC-TED’) for combating SARS-CoV-2-induced cell reprogramming

Costa

Mohanapriya

Bharadwaj

et al. 2021

Preprint

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“…In recent years, it has become increasing evident that coronaviruses utilize various host cell components for their own replicative benefit (6,41,42). Previous studies have shown that RNA viruses may also harbour the ability to hijack the functions of host cellular miRNAs to their advantage.…”

Section: The S2m Element Of Sars-cov-2 Interacts With Cellular Mirna-mentioning

confidence: 99%

SARS-CoV-2 highly conserved s2m element dimerizes via a kissing complex and interacts with host miRNA-1307-3p

Imperatore

Cunningham

Pellegrene

et al. 2020

Preprint

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The ongoing COVID-19 pandemic highlights the necessity for a more fundamental understanding of the coronavirus life cycle. The causative agent of the disease, SARS-CoV-2, is being studied extensively from a structural standpoint in order to gain insight into key molecular mechanisms required for its survival. Contained within the untranslated regions of the SARS-CoV-2 genome are various conserved stem-loop elements that are believed to function in RNA replication, viral protein translation, and discontinuous transcription. While the majority of these regions are variable in sequence, a 41-nucleotide s2m element within the 3’ UTR is highly conserved among coronaviruses and three other viral families. In this study, we demonstrate that the s2m element of SARS-CoV-2 dimerizes by forming an intermediate homodimeric kissing complex structure that is subsequently converted to a thermodynamically stable duplex conformation. This process is aided by the viral nucleocapsid protein, potentially indicating a role in mediating genome dimerization. Furthermore, we demonstrate that the s2m element interacts with multiple copies of host cellular miRNA-1307-3p. Taken together, our results highlight the potential significance of the dimer structures formed by the s2m element in key biological processes and implicate the motif as a possible therapeutic drug target for COVID-19 and other coronavirus-related diseases.

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“…This approach has been implemented in Laise et al . [ 99 ] where the authors used transcriptome data from Calu-3 lung adenocarcinoma cells infected with SARS-CoV to identify master regulator proteins related to SARS-CoV infection process.…”

Section: Therapeutic Target Identificationmentioning

confidence: 99%

A review of COVID-19 biomarkers and drug targets: resources and tools

Caruso

Scala

Cerulo

et al. 2020

Briefings in Bioinformatics

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The stratification of patients at risk of progression of COVID-19 and their molecular characterization is of extreme importance to optimize treatment and to identify therapeutic options. The bioinformatics community has responded to the outbreak emergency with a set of tools and resource to identify biomarkers and drug targets that we review here. Starting from a consolidated corpus of 27 570 papers, we adopt latent Dirichlet analysis to extract relevant topics and select those associated with computational methods for biomarker identification and drug repurposing. The selected topics span from machine learning and artificial intelligence for disease characterization to vaccine development and to therapeutic target identification. Although the way to go for the ultimate defeat of the pandemic is still long, the amount of knowledge, data and tools generated so far constitutes an unprecedented example of global cooperation to this threat.

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The Host Cell ViroCheckpoint: Identification and Pharmacologic Targeting of Novel Mechanistic Determinants of Coronavirus-Mediated Hijacked Cell States

Cited by 17 publications

References 79 publications

ROS/RNS balancing, aerobic fermentation regulation and cell cycle control – a complex early trait (‘CoV-MAC-TED’) for combating SARS-CoV-2-induced cell reprogramming

ROS/RNS balancing, aerobic fermentation regulation and cell cycle control – a complex early trait (‘CoV-MAC-TED’) for combating SARS-CoV-2-induced cell reprogramming

SARS-CoV-2 highly conserved s2m element dimerizes via a kissing complex and interacts with host miRNA-1307-3p

A review of COVID-19 biomarkers and drug targets: resources and tools

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