Unpacking Pandora from Its Box: Deciphering the Molecular Basis of the SARS-CoV-2 Coronavirus

O’Leary, Valerie B.; Dolly, J. Oliver; Höschl, Cyril; Černá, Marie; Ovsepian, Saak V.

doi:10.3390/ijms22010386

Cited by 12 publications

(12 citation statements)

References 85 publications

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“…Like the other diseases caused by coronaviruses, COVID-19 is thought to be of zoonotic origin (Contini et al, 2020;Decaro & Lorusso, 2020;Mahdy et al, 2020;Swelum et al, 2020;Zhou et al, 2020). The assessment of risks of human-to-human, animal-to-human, and human-to-animal transmission of coronaviral infections and development of efficient medications and vaccines against the coronaviruses need the knowledge of main molecular mechanisms in the virus life cycle and virus-host interactions (Mishra & Tripathi, 2021;O'Leary et al, 2020;Rabi et al, 2020;Saxena, 2020).…”

Section: Introductionmentioning

confidence: 99%

Evolving ribonucleocapsid assembly/packaging signals in the genomes of the human and animal coronaviruses: targeting, transmission and evolution

Chechetkin

Lobzin

2021

Journal of Biomolecular Structure and Dynamics

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A world-wide COVID-19 pandemic intensified strongly the studies of molecular mechanisms related to the coronaviruses. The origin of coronaviruses and the risks of human-to-human, animal-to-human, and human-to-animal transmission of coronaviral infections can be understood only on a broader evolutionary level by detailed comparative studies. In this paper, we studied ribonucleocapsid assembly-packaging signals (RNAPS) in the genomes of all seven known pathogenic human coronaviruses, SARS-CoV, SARS-CoV-2, MERS-CoV, HCoV-OC43, HCoV-HKU1, HCoV-229E, and HCoV-NL63 and compared them with RNAPS in the genomes of the related animal coronaviruses including SARS-Bat-CoV, MERS-Camel-CoV, MHV, Bat-CoV MOP1, TGEV, and one of camel alphacoronaviruses. RNAPS in the genomes of coronaviruses were evolved due to weakly specific interactions between genomic RNA and N proteins in helical nucleocapsids. Combining transitional genome mapping and Jaccard correlation coefficients allows us to perform the analysis directly in terms of underlying motifs distributed over the genome. In all coronaviruses RNAPS were distributed quasi-periodically over the genome with the period about 54 nt biased to 57 nt and to 51 nt for the genomes longer and shorter than that of SARS-CoV, respectively. The comparison with the experimentally verified packaging signals for MERS-CoV, MHV, and TGEV proved that the distribution of particular motifs is strongly correlated with the packaging signals. We also found that many motifs were highly conserved in both characters and positioning on the genomes throughout the lineages that make them promising therapeutic targets. The mechanisms of encapsidation can affect the recombination and co-infection as well.

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Section: Introductionmentioning

confidence: 99%

Evolving ribonucleocapsid assembly/packaging signals in the genomes of the human and animal coronaviruses: targeting, transmission and evolution

Chechetkin

Lobzin

2021

Journal of Biomolecular Structure and Dynamics

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“…The N protein is the most abundant protein expressed by SARS-CoV-2 in infected cells. It plays a crucial role in packaging the viral RNA genome into long, flexible, helical ribonucleoprotein (RNP) complexes [12,13]. Three distinct and highly conserved domains were identified in this protein: a N-terminal domain (NTD), a C-terminal domain (CTD) and an RNA-binding domain (RBD).…”

Section: Sars-cov-2 Drug Targetsmentioning

confidence: 99%

“…The M protein is the most abundant protein in the virion envelope and has three transmembrane domains and a large carboxyl-terminal tail. It plays a fundamental role in virion assembly and might also display ion channel activity [12,14]. In addition, recent evidence suggests that M protein, in association with N protein, may play a role in assembly of the nucleocapsid core into progeny virions [14].…”

Section: Sars-cov-2 Drug Targetsmentioning

confidence: 99%

Drug Repurposing for COVID-19: A Review and a Novel Strategy to Identify New Targets and Potential Drug Candidates

et al. 2022

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In December 2019, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19) was first identified in the province of Wuhan, China. Since then, there have been over 400 million confirmed cases and 5.8 million deaths by COVID-19 reported worldwide. The urgent need for therapies against SARS-CoV-2 led researchers to use drug repurposing approaches. This strategy allows the reduction in risks, time, and costs associated with drug development. In many cases, a repurposed drug can enter directly to preclinical testing and clinical trials, thus accelerating the whole drug discovery process. In this work, we will give a general overview of the main developments in COVID-19 treatment, focusing on the contribution of the drug repurposing paradigm to find effective drugs against this disease. Finally, we will present our findings using a new drug repurposing strategy that identified 11 compounds that may be potentially effective against COVID-19. To our knowledge, seven of these drugs have never been tested against SARS-CoV-2 and are potential candidates for in vitro and in vivo studies to evaluate their effectiveness in COVID-19 treatment.

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“…The pandemic is still continuing and the second and third waves of diseases are pending in many countries. The development of efficient medications and vaccines against the coronaviruses needs the knowledge of main molecular mechanisms in the virus life cycle and virus-host interaction [24][25][26][27].…”

Section: Quasi-periodic Motifs In the Genomes Of The Coronaviruses Sars-cov And Sars-cov-2mentioning

confidence: 99%

Combining detection and reconstruction of correlational and periodic motifs in viral genomic sequences with transitional genome mapping: Application to COVID-19

Lobzin

2021

JIOMICS

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A method of Transitional Automorphic Mapping of the Genome on Itself (TAMGI) is aimed at combining detection and reconstruction of correlational and quasi-periodic motifs in the viral genomic RNA/DNA sequences. The motifs reconstructed by TAMGI are robust with respect to indels and point mutations and can be tried as putative therapeutic targets. We developed and tested the relevant theory and statistical criteria for TAMGI applications. The applications of TAMGI are illustrated by the study of motifs in the genomes of the severe acute respiratory syndrome coronaviruses SARS-CoV and SARS-CoV-2 (the latter coronavirus SARS-CoV-2 being responsible for the COVID-19 pandemic) packaged within filament-like helical capsid. Such ribonucleocapsid is transported into spherical membrane envelope with incorporated spike glycoproteins. Two other examples concern the genomes of viruses with icosahedral capsids, satellite tobacco mosaic virus (STMV) and bacteriophage PHIX174. A part of the quasi-periodic motifs in these viral genomes was evolved due to weakly specific cooperative interaction between genomic ssRNA/ssDNA and nucleocapsid proteins. The symmetry of the capsids leads to the natural selection of specific quasi-periodic motifs in the related genomic sequences. Generally, TAMGI provides a convenient tool for the study of numerous molecular mechanisms with participation of both quasi-periodic motifs and complete repeats, the genome organization, contextual analysis of cis/trans regulatory elements, data mining, and correlations in the genomic sequences.

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Unpacking Pandora from Its Box: Deciphering the Molecular Basis of the SARS-CoV-2 Coronavirus

Cited by 12 publications

References 85 publications

Evolving ribonucleocapsid assembly/packaging signals in the genomes of the human and animal coronaviruses: targeting, transmission and evolution

Evolving ribonucleocapsid assembly/packaging signals in the genomes of the human and animal coronaviruses: targeting, transmission and evolution

Drug Repurposing for COVID-19: A Review and a Novel Strategy to Identify New Targets and Potential Drug Candidates

Combining detection and reconstruction of correlational and periodic motifs in viral genomic sequences with transitional genome mapping: Application to COVID-19

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