Molecular characterization of SARS-CoV-2 from the first case of COVID-19 in Italy

Capobianchi, Maria Rosaria; Rueca, Martina; Messina, Francesco; Giombini, Emanuela; Carletti, Fabrizio; Colavita, Francesca; Castilletti, Concetta; Lalle, Eleonora; Bordi, Licia; Vairo, Francesco; Nicastri, Emanuele; Ippolito, Giuseppe; Gruber, Cesare Ernesto Maria; Bartolini, Barbara

doi:10.1016/j.cmi.2020.03.025

Cited by 102 publications

(108 citation statements)

References 5 publications

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“…The latter possibility is further supported by our results, which showed a significantly high number of non-synonymous variants at the sub-consensus level, none of which were seen at the consensus level. Similar findings were also reported in other SARS-CoV-2 studies (Sigal et al, 2018 ; Capobianchi et al, 2020 ; Shen et al, 2020 ). Still, other research groups were able to find variability hotspots in SARS-CoV-2 genomes (Ceraolo and Giorgi, 2020 ; van Dorp et al, 2020 ).…”

Section: Discussionsupporting

confidence: 90%

“…One of the earliest studies that were carried in Wuhan during December 2019 also reported the presence of within-host variants (range from 0 to 51 variants per patient) in hospitalized COVID-19 patients (Shen et al, 2020 ). Similarly, analysis of the first two cases from Lombardy, Italy, also revealed the presence of virus quasispecies; however, with limited variation compared to our study (Capobianchi et al, 2020 ). The lower number of reported within-host variants in the latter study is most probably related to the small number of samples, the different sequencing protocols, and the low coverage of sequencing reads.…”

Section: Discussionsupporting

confidence: 57%

“…Nonetheless, in-depth analysis revealed the presence of sub-consensus variants in both mild and severe cases but at significantly higher numbers among severe cases. The existence of viral quasispecies has been reported, although not frequently, in COVID-19 patients (Capobianchi et al, 2020 ; Ceraolo and Giorgi, 2020 ; Shen et al, 2020 ; van Dorp et al, 2020 ). One of the earliest studies that were carried in Wuhan during December 2019 also reported the presence of within-host variants (range from 0 to 51 variants per patient) in hospitalized COVID-19 patients (Shen et al, 2020 ).…”

Section: Discussionmentioning

confidence: 98%

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Within-Host Diversity of SARS-CoV-2 in COVID-19 Patients With Variable Disease Severities

Al-Khatib

Benslimane

Elbashir

et al. 2020

Front. Cell. Infect. Microbiol.

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Background: The ongoing pandemic of SARS-COV-2 has already infected more than eight million people worldwide. The majority of COVID-19 patients either are asymptomatic or have mild symptoms. Yet, about 15% of the cases experience severe complications and require intensive care. Factors determining disease severity are not yet fully characterized. Aim: Here, we investigated the within-host virus diversity in COVID-19 patients with different clinical manifestations. Methods: We compared SARS-COV-2 genetic diversity in 19 mild and 27 severe cases. Viral RNA was extracted from nasopharyngeal samples and sequenced using the Illumina MiSeq platform. This was followed by deep-sequencing analyses of SARS-CoV-2 genomes at both consensus and sub-consensus sequence levels. Results: Consensus sequences of all viruses were very similar, showing more than 99.8% sequence identity regardless of the disease severity. However, the sub-consensus analysis revealed significant differences in within-host diversity between mild and severe cases. Patients with severe symptoms exhibited a significantly ( p -value 0.001) higher number of variants in coding and non-coding regions compared to mild cases. Analysis also revealed higher prevalence of some variants among severe cases. Most importantly, severe cases exhibited significantly higher within-host diversity (mean = 13) compared to mild cases (mean = 6). Further, higher within-host diversity was observed in patients above the age of 60 compared to the younger age group. Conclusion: These observations provided evidence that within-host diversity might play a role in the development of severe disease outcomes in COVID-19 patients; however, further investigations are required to elucidate this association.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 98%

See 1 more Smart Citation

Within-Host Diversity of SARS-CoV-2 in COVID-19 Patients With Variable Disease Severities

Al-Khatib

Benslimane

Elbashir

et al. 2020

Front. Cell. Infect. Microbiol.

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“…Specifically, SARS-CoV-2 sequencing along with its relative intrinsic genomic variability [10], the presence of minority variants generated during SARS-CoV-2 replication [11], the involved cellular factors that favors SARS-CoV-2 cell entry [12], the timing in which viral load peaks (during the first week of illness), its gradual decline (over the second week) and the increasing of both IgG and IgM antibodies (around day 10 after symptom onset) represent some of the relevant insights so far delineated and considered by research community about SARS-CoV-2 virus [13].…”

Section: Introductionmentioning

confidence: 99%

In Silico Trial to test COVID-19 candidate vaccines: a case study with UISS platform

Russo

Pennisi

Viceconti

et al. 2020

Preprint

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SARS-CoV-2 is a severe respiratory infection that infects humans. Its outburst entitled it as a pandemic emergence. To get a grip on this outbreak, specific preventive and therapeutic interventions are urgently needed. It must be said that, until now, there are no existing vaccines for coronaviruses. To promptly and rapidly respond to pandemic events, the application of in silico trials can be used for designing and testing medicines against SARS-CoV-2 and speed-up the vaccine discovery pipeline, predicting any therapeutic failure and minimizing undesired effects. Here, we present an in silico platform that showed to be in very good agreement with the latest literature in predicting SARS-CoV-2 dynamics and related immune system host response. Moreover, it has been used to predict the outcome of one of the latest suggested approach to design an effective vaccine, based on monoclonal antibody. Universal Immune System Simulator (UISS) in silico platform is potentially ready to be used as an in silico trial platform to predict the outcome of vaccination strategy against SARS-CoV-2.Index Terms-Agent-Based Model, human monoclonal antibodies, In Silico Trials, SARS-CoV-2, vaccines.

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“…Considering the continuous increase of infected people and the high variability of the virus, it is important to pay attention to the genomic changes of SARS-CoV-2. Recently, 7 substitution hotspots in SARS-CoV-2, ORF1ab-G10818T (ORF1ab-L3606F), ORF1ab-C8517T, ORF3a-G752T (ORF3a-G251V) S-A1841G (D614G), G171T (Q57H), ORF8-T251C (ORF8-L84S) and N-GGG608_609_610AAC ( N -RG203_204KR) have been reported [29–32]. In addition, the non-synonymous substitution of ORF3a-G251V and ORF8-L84S both cause the amino acid (aa) polarity changing, which may affect the conformation of the protein and lead to function altering [31].…”

Section: Introductionmentioning

confidence: 99%

Characterization of the substitution hotspots in SARS-CoV-2 genome using BioAider and detection of a SR-rich region in N protein providing further evidence of its animal origin

Zhou

Qiu

2020

Preprint

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The novel human coronavirus (SARS-CoV-2) causes the coronavirus disease 2019 (COVID-19) pandemic worldwide. The increasing sequencing data have shown abundant single nucleotide variations in SARS-CoV-2 genome. However, it is difficult to quickly analyze genomic variation and screen key mutations of SARS-CoV-2. In this study, we developed a visual program, named BioAider, for quick and convenient sequence annotation and mutation analysis on multiple genome-sequencing data. Using BioAider, we conducted a comprehensive genome variation analysis on 3,240 sequences of SARS-CoV-2 genome. Herein, we detected 14 substitution hotspots within SARS-CoV-2 genome, including 10 non-synonymous and 4 synonymous ones. Among these hotspots, NSP13-Y541C was predicted to be a crucial substitution which might affect the unwinding activity of NSP13, a key protein for viral replication. Besides, we also found 3 groups of potentially linked substitution hotspots which were worth further study. In particular, we discovered a SR-rich region (aa 184-204) on the N protein of SARS-CoV-2 distinct from SARS-CoV, indicating more complex replication mechanism and unique N-M interaction of SARS-CoV-2. Interestingly, the quantity of SRXX repeat fragments in the SR-rich region well reflected the evolutionary relationship among SARS-CoV-2 and SARS-CoV-2 related animal coronaviruses, providing further evidence of its animal origin. Overall, we developed an efficient tool for rapid identification of mutations, identified substitution hotspots in SARS-CoV-2 genomes, and detected a distinctive polymorphism SR-rich region in N protein. This tool and the detected hotspots could facilitate the viral genomic study and may contribute for screening antiviral target sites.

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Molecular characterization of SARS-CoV-2 from the first case of COVID-19 in Italy

Cited by 102 publications

References 5 publications

Within-Host Diversity of SARS-CoV-2 in COVID-19 Patients With Variable Disease Severities

Within-Host Diversity of SARS-CoV-2 in COVID-19 Patients With Variable Disease Severities

In Silico Trial to test COVID-19 candidate vaccines: a case study with UISS platform

Characterization of the substitution hotspots in SARS-CoV-2 genome using BioAider and detection of a SR-rich region in N protein providing further evidence of its animal origin

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