Viral G-quadruplexes: New frontiers in virus pathogenesis and antiviral therapy

Ruggiero, Emanuela; Richter, Sara N.

doi:10.1016/bs.armc.2020.04.001

Cited by 75 publications

(79 citation statements)

References 89 publications

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“…Both G-quadruplexes and hairpins formed by IRs are recognized by many cellular proteins [ 19 , 26 , 54 ]. Although IRs are essential for viral genome organization, it seems that G-quadruplexes have been effectively eliminated in order to help the virus to circumvent cellular immunity [ 23 , 55 , 56 ]. Nevertheless, the association of hot-spot mutations with IR loci suggests also selective pressure against hairpins at specific locations.…”

Section: Resultsmentioning

confidence: 99%

SARS-CoV-2 hot-spot mutations are significantly enriched within inverted repeats and CpG island loci

Goswami

Bartas

Lexa

et al. 2020

Briefings in Bioinformatics

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SARS-CoV-2 is an intensively investigated virus from the order Nidovirales ( Coronaviridae family) that causes COVID-19 disease in humans. Through enormous scientific effort, thousands of viral strains have been sequenced to date, thereby creating a strong background for deep bioinformatics studies of the SARS-CoV-2 genome. In this study, we inspected high-frequency mutations of SARS-CoV-2 and carried out systematic analyses of their overlay with inverted repeat (IR) loci and CpG islands. The main conclusion of our study is that SARS-CoV-2 hot-spot mutations are significantly enriched within both IRs and CpG island loci. This points to their role in genomic instability and may predict further mutational drive of the SARS-CoV-2 genome. Moreover, CpG islands are strongly enriched upstream from viral ORFs and thus could play important roles in transcription and the viral life cycle. We hypothesize that hypermethylation of these loci will decrease the transcription of viral ORFs and could therefore limit the progression of the disease.

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Section: Resultsmentioning

confidence: 99%

SARS-CoV-2 hot-spot mutations are significantly enriched within inverted repeats and CpG island loci

Goswami

Bartas

Lexa

et al. 2020

Briefings in Bioinformatics

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“…The SARS-CoV-2 coronavirus is the key culprit responsible for the outbreak, and no specific inhibitor drugs have been developed yet. G-quadruplexes have shown tremendous potential for the development of anticancer [59][60][61][62] and antiviral drugs [44,63,64], as Gquadruplexes can interfere with many biological processes that are critical to cancer cells and viruses. Therefore, it is necessary to quantify and characterize the PG4s in the SARS-CoV-2 genome to provide a possible novel method for the treatment of COVID-19.…”

Section: Discussionmentioning

confidence: 99%

Whole genome identification of potential G-quadruplexes and analysis of the G-quadruplex binding domain for SARS-CoV-2

Zhang

Xiao

et al. 2020

Preprint

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The Coronavirus Disease 2019 pandemic caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) quickly become a global public health emergency. Gquadruplex, one of the non-canonical secondary structures, has shown potential antiviral values. However, little is known about G-quadruplexes on the emerging SARS-CoV-2. Herein, we characterized the potential G-quadruplexes both in the positive and negative-sense viral stands. The identified potential G-quadruplexes exhibits similar features to the G-quadruplexes detected in the human transcriptome. Within some bat and pangolin related beta coronaviruses, the G-quartets rather than the loops are under heightened selective constraints. We also found that the SUD-like sequence is retained in the SARS-CoV-2 genome, while some other coronaviruses that can infect humans are depleted. Further analysis revealed that the SARS-CoV-2 SUD-like sequence is almost conserved among 16,466 SARS-CoV-2 samples. And the SARS-CoV-2 SUDcore-like dimer displayed similar electrostatic potential pattern to the SUD dimer. Considering the potential value of G-quadruplexes to serve as targets in antiviral strategy, we hope our fundamental research could provide new insights for the SARS-CoV-2 drug discovery. Respiratory Syndrome (MERS) in 2012 [2,5], and COVID-19. Scientists identified and sequenced the virus early in this outbreak, and named it SARS-CoV-2[6]. The symptoms of the patients infected with the novel coronavirus vary from person to person, and fever, cough, and fatigue are the most common ones[7-10]. The clinical chest CT (Computed tomography) and nucleic acid testing are the most typical methods of diagnosing 10]. It is worth noting that the recent achievements in AI (Artificial Intelligence) aid diagnosis technology[11] and CRISPR-Cas12-based detection methods [12] are expected to expand the diagnosis of COVID-19. Despite the great efforts of the researchers, so far, no specific clinical drugs or vaccines have been developed to cope with COVID-19. SARS-CoV-2 is a Betacoronavirus within the Coronaviridae family that is the culprit responsible for the COVID-19 pandemic [13,14] (Fig. 1A). Studies have confirmed that SARS-CoV-2 is a positive-sense single-stranded RNA ((+)ssRNA) virus with a total length of approximately 30k. The positive-sense RNA strand of SARS-CoV-2 can serve as a template to produce viral proteins related to replication, structure composition, and other functions or events [15,16]. One of the hotspots is how the SARS-CoV-2 entry the host cells. SARS-CoV-2 has shown a great affinity to the angiotensin-converting enzyme 2 (ACE2), which has been proved to be the binding receptor for SARS-CoV-2 [17,18]. After entering the host cells, the viral genomic RNA will be released to the cytoplasm, and the ORF1a/ORF1ab are subsequently translated into replicase polyproteins of pp1a/pp1ab, which will be cleaved into some non-structural proteins (nsps). These non-structure proteins ultimately form the replicase-transcriptase complex for replication and transcription....

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“…A G4 structure in Epstein-Barr virus (EBV) functioned as a cis-acting regulatory region to translate EBV encoded nuclear antigen 1 (EBNA1) mRNA (Murat et al, 2014). G4 structures have also been observed in human papillomavirus (HPV), hepatitis B virus (HBV), Nipah virus, hepatitis C virus (HCV), Zika virus, and Ebola virus (Ruggiero and Richter, 2020). These studies highlight a critical role for G4 structures in viruses.…”

Section: Introductionmentioning

confidence: 99%

G-Quadruplexes Are Present in Human Coronaviruses Including SARS-CoV-2

Cui

Zhang

2020

Front. Microbiol.

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The global coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is one of seven human coronaviruses. G-quadruplexes are intrinsic obstacles to genome replication. Whether G-quadruplexes are present in human coronaviruses is unknown. In the current study, we have predicted that all seven human coronaviruses harbor G-quadruplex sequences. Conserved G-quadruplex sequences in SARS-CoV and SARS-CoV-2 were analyzed and verified by circular dichroism (CD) spectroscopy and Thioflavin T fluorescence assay. Similar to SARS-CoV, SARS-CoV-2 encodes an nsP3 protein, which is predicted to associate with G-quadruplexes. Targeting G-quadruplex sequences in the SARS-CoV-2 genome by G-quadruplex ligands could be a new way to conquer COVID-19.

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Viral G-quadruplexes: New frontiers in virus pathogenesis and antiviral therapy

Abstract: Introduction 101 2. DNA viruses 104 2.1 Herpesviruses 106 2.2 Other DNA viruses 112 3. RNA viruses 113 3.1 Flaviviruses 113 3.2 Filoviruses 117 3.3 SARS coronavirus 117 4. Retroviruses 118 4.1 Lentiviruses 119 5. Discussion and final remarks 123 References 126

Cited by 75 publications

References 89 publications

SARS-CoV-2 hot-spot mutations are significantly enriched within inverted repeats and CpG island loci

SARS-CoV-2 hot-spot mutations are significantly enriched within inverted repeats and CpG island loci

Whole genome identification of potential G-quadruplexes and analysis of the G-quadruplex binding domain for SARS-CoV-2

G-Quadruplexes Are Present in Human Coronaviruses Including SARS-CoV-2

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