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Full-genome evolutionary analysis of the novel corona virus (2019-nCoV) rejects the hypothesis of emergence as a result of a recent recombination event

DOI:10.1016/j.meegid.2020.104212
Authors:
Dimitrios Paraskevis at National and Kapodistrian University of Athens
Dimitrios Paraskevis
Evangelia Georgia Kostaki at National and Kapodistrian University of Athens
Evangelia Georgia Kostaki
Gkikas Magiorkinis at National and Kapodistrian University of Athens
Gkikas Magiorkinis
G. Panayiotakopoulos
G. Panayiotakopoulos
G. Panayiotakopoulos
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Background: A novel coronavirus (2019-nCoV) associated with human to human transmission and severe human infection has been recently reported from the city of Wuhan in China. Our objectives were to characterize the genetic relationships of the 2019-nCoV and to search for putative recombination within the subgenus of sarbecovirus. Methods: Putative recombination was investigated by RDP4 and Simplot v3.5.1 and discordant phylogenetic clustering in individual genomic fragments was confirmed by phylogenetic analysis using maximum likelihood and Bayesian methods. Results: Our analysis suggests that the 2019-nCoV although closely related to BatCoV RaTG13 sequence throughout the genome (sequence similarity 96.3%), shows discordant clustering with the Bat_SARS-like coronavirus sequences. Specifically, in the 5'-part spanning the first 11,498 nucleotides and the last 3'-part spanning 24,341-30,696 positions, 2019-nCoV and RaTG13 formed a single cluster with Bat_SARS-like coronavirus sequences, whereas in the middle region spanning the 3'-end of ORF1a, the ORF1b and almost half of the spike regions, 2019-nCoV and RaTG13 grouped in a separate distant lineage within the sarbecovirus branch. Conclusions: The levels of genetic similarity between the 2019-nCoV and RaTG13 suggest that the latter does not provide the exact variant that caused the outbreak in humans, but the hypothesis that 2019-nCoV has originated from bats is very likely. We show evidence that the novel coronavirus (2019-nCov) is not-mosaic consisting in almost half of its genome of a distinct lineage within the betacoronavirus. These genomic features and their potential association with virus characteristics and virulence in humans need further attention.
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Contents lists available at ScienceDirect
Infection, Genetics and Evolution
journal homepage: www.elsevier.com/locate/meegid
Short communication
Full-genome evolutionary analysis of the novel corona virus (2019-nCoV)
rejects the hypothesis of emergence as a result of a recent recombination
event
D. Paraskevis
a,⁎
, E.G. Kostaki
a
, G. Magiorkinis
a
, G. Panayiotakopoulos
b
, G. Sourvinos
c
,
S. Tsiodras
d
a
Department of Hygiene Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece
b
National Public Health Organization (NPHO), Athens, Greece
c
Laboratory of Clinical Virology, School of Medicine, University of Crete, Heraklion, Greece
d
Medical School, National and Kapodistrian University of Athens, Athens, Greece
ARTICLE INFO
Keywords:
Novel coronavirus
Genomic sequence analysis
Phylogenetic analysis
Recombination
Origin
Molecular epidemiology
ABSTRACT
Background: A novel coronavirus (2019-nCoV) associated with human to human transmission and severe human
infection has been recently reported from the city of Wuhan in China. Our objectives were to characterize the
genetic relationships of the 2019-nCoV and to search for putative recombination within the subgenus of sar-
becovirus.
Methods: Putative recombination was investigated by RDP4 and Simplot v3.5.1 and discordant phylogenetic
clustering in individual genomic fragments was confirmed by phylogenetic analysis using maximum likelihood
and Bayesian methods.
Results: Our analysis suggests that the 2019-nCoV although closely related to BatCoV RaTG13 sequence
throughout the genome (sequence similarity 96.3%), shows discordant clustering with the Bat_SARS-like cor-
onavirus sequences. Specifically, in the 5′-part spanning the first 11,498 nucleotides and the last 3′-part spanning
24,341–30,696 positions, 2019-nCoV and RaTG13 formed a single cluster with Bat_SARS-like coronavirus se-
quences, whereas in the middle region spanning the 3′-end of ORF1a, the ORF1b and almost half of the spike
regions, 2019-nCoV and RaTG13 grouped in a separate distant lineage within the sarbecovirus branch.
Conclusions: The levels of genetic similarity between the 2019-nCoV and RaTG13 suggest that the latter does not
provide the exact variant that caused the outbreak in humans, but the hypothesis that 2019-nCoV has originated
from bats is very likely. We show evidence that the novel coronavirus (2019-nCov) is not-mosaic consisting in
almost half of its genome of a distinct lineage within the betacoronavirus. These genomic features and their
potential association with virus characteristics and virulence in humans need further attention.
The family Coronaviridae includes a large number of viruses that in
nature are found in birds and mammals (Kahn and McIntosh, 2005;
Fehr and Perlman, 2015). Human coronaviruses, first characterized in
the 1960s, are associated with a large percentage of respiratory infec-
tions both in children and adults (Kahn and McIntosh, 2005;Paules
et al., 2020).
Scientific interest in Coronaviruses exponentially increased after the
emergence of SARS-Coronavirus (SARS-CoV) in Southern China
(Drosten et al., 2003;Ksiazek et al., 2003;Peiris et al., 2003). Its rapid
spread led to the global appearance of more than 8000 human cases and
774 deaths (Kahn and McIntosh, 2005). The virus was initially detected
in Himalayan palm civets (Guan et al., 2003) that may have served as
an amplification host; the civet virus contained a 29-nucleotide se-
quence not found in most human isolates that were related to the global
epidemic (Guan et al., 2003). It has been speculated that the function of
the affected open reading frame (ORF 10) might have played a role in
the trans-species jump (Kahn and McIntosh, 2005). A similar virus was
found later in horseshoe bats (Lau et al., 2005;Li et al., 2005a). A 29-bp
insertion in ORF 8 of bat-SARS-CoV genome, not found in most human
SARS-CoV genomes, was suggestive of a common ancestor with civet
SARS-CoV (Lau et al., 2005). After the SARS epidemic, bats have been
considered as a potential reservoir species that could be implicated in
https://doi.org/10.1016/j.meegid.2020.104212
Received 27 January 2020; Accepted 28 January 2020
⁎
Corresponding author at: Department of Hygiene, Epidemiology and Medical Statistics, Medical School, University of Athens, 75 Mikras Asias Street, 115 27
Athens, Greece.
E-mail address: dparask@med.uoa.gr (D. Paraskevis).
Infection, Genetics and Evolution 79 (2020) 104212
Available online 29 January 2020
1567-1348/ © 2020 Elsevier B.V. All rights reserved.
T
future coronavirus-related human pandemics (Cui et al., 2019). During
2012 Middle East Respiratory coronavirus (MERS-CoV) emerged in
Saudi Arabia (Zaki et al., 2012;Hajjar et al., 2013) and has since
claimed the lives of 919 out of 2521 (35%) people affected (ECDC,
2020). A main role in the transmission of the virus to humans has been
attributed to dromedary camels (Alagaili et al., 2014) and its origin has
been again traced to bats (Ithete et al., 2013).
Ever since both SARS and MERS-CoV (due to their high case fatality
rates) are prioritized together with “highly pathogenic coronaviral
diseases other than MERS and SARS”under the Research and
Development Blueprint published by the WHO (World Health
Organization, 2018).
A novel coronavirus (2019-nCoV) associated with human to human
transmission and severe human infection has been recently reported
from the city of Wuhan in Hubei province in China (World Health
Organization, 2020;Hui et al., 2020). A total of 1,320 confirmed and
1,965 suspect cases were reported up to 25 January 2020; of the con-
firmed cases 237 were severely ill and 41 had died (World Health
Organization, 2020). Most of the original cases had close contact with a
local fresh seafood and an animal market (Zhu et al., 2020;Perlman,
2020).
Full-genome sequence analysis of 2019-nCoV revealed that belongs
to betacoronavirus, but it is divergent from SARS-CoV and MERS-CoV
that caused epidemics in the past (Zhu et al., 2020). The 2019-nCoV
along with the Bat_SARS-like coronavirus forms a distinct lineage
within the subgenus of the sarbecovirus (Zhu et al., 2020).
Our objectives were to characterize the genetic relationships of the
2019-nCoV and to search for putative recombination within the sub-
genus of sarbecovirus.
Viral sequences were downloaded from NCBI nucleotide sequence
database (http://www.ncbi.nlm.nih.gov). The BatCoV RaTG13
sequence was downloaded from the GISAID BetaCov 2019–2020 re-
pository (http://www.GISAID.org). The sequence was reported in Zhou
et al. (2020). Full-genomic sequence alignment was performed using
MAFFT v7.4.2. (Katoh and Standley, 2013) and manually edited using
MEGA v1.0 (Stecher et al., 2020) according to the encoded reading
frame. Putative recombination was investigated by RDP4 (Martin,
2015) and Simplot v3.5.1 (Lole et al., 1999) and discordant phyloge-
netic clustering in individual genomic fragments was confirmed by
phylogenetic analysis using maximum likelihood (ML) and Bayesian
methods. ML trees were reconstructed using Neighbor-Joining (NJ)
with ML distances or after heuristic ML search (TBR) with GTR + G as
nucleotide substitution model as implemented in PAUP* 4.0 beta
(Swofford, 2003). The GTR + G was used in Bayesian analysis as im-
plemented in MrBayes v3.2.7 (Huelsenbeck and Ronquist, 2001). Phy-
logenetic trees were viewed using FigTree v1.4 (http://tree.bio.ed.ac.
uk/software/figtree/).
A similarity plot was performed using a sliding window of 450 nts
moving in steps of 50 nts, between the query sequence (2019-nCoV)
and different sequences grouped according to their clustering pattern.
The similarity plot (Fig. 1A,B) suggested that the RaTG13 was the most
closely related sequence to the 2019-nCoV throughout the genome. The
genetic similarity between the 2019-nCoV and RaTG13 was 96.3% (p-
distance: 0.0369). On the other hand, a discordant relationship was
detected between the query and the sequences of the Bat_SARS-like
coronavirus (MG772934 and MG772933) (Fig. 1C). Specifically in in
the 5′-part of the genome spanning the first 10,901 nts of the alignment
that correspond to the 11,498 nucleotides of the prototype strain
(NC_045512) and the last 3′-part spanning 22,831–27,933 positions
(24,341–30,696 nucleotides in the NC_045512), 2019-nCoV and
RaTG13 formed a single cluster with Bat_SARS-like coronavirus se-
quences (Fig. 1C). In the middle region spanning the 3′-end of ORF1a,
Fig. 1. A. Genomic organization of the novel coronavirus (2019-nCoV) according to the positions in the edited alignment. B. Simplot of 2019-nCoV
(NC_045512_Wuhan_Hu-1) against sequences within the subgenus sarbecovirus. Different colours correspond to the nucleotide similarity between the 2019-nCoV and
different groups. The regions with discordant phylogenetic clustering of the 2019-nCoV with Bats_SARS-like sequences are shown in different colours. C. Maximum
likelihood (ML) phylogenetic trees inferred in different genomic regions as indicated by the Simplot analysis. The genomic regions are shown in numbers at the top or
at the left of the trees. The 2019-nCoV sequence is shown in red and stars indicate important nodes received 100% bootstrap and 1 posterior probability support. (For
interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
D. Paraskevis, et al. Infection, Genetics and Evolution 79 (2020) 104212
2
the ORF1b and almost half of the spike regions (10,901–22,830 nts in
the alignment or 11,499–24,340 of the NC_045512), 2019-nCoV and
RaTG13 grouped in a separate distant lineage within the sarbecovirus
branch (Fig. 1B, C). In this region the 2019-nCoV and RaTG13 is dis-
tantly related to the Bat_SARS-like coronavirus sequences. Phylogenetic
analyses using different methods confirmed these findings. A BLAST
search of 2019-nCoV middle fragment revealed no considerable simi-
larity with any of the previously characterized corona viruses (Fig. 2).
Our study suggests that the new corona virus (2019-nCoV) is not a
mosaic and it is most closely related with the BatCoV RaTG13 detected
in bats from Yunnan Province (Zhou et al., 2020). The levels of genetic
similarity between the 2019-nCoV and RaTG13 suggest that the latter
does not provide the exact variant that caused the outbreak in humans,
but the hypothesis that 2019-nCoV has originated from bats is very
likely. On the other hand, there is evidence for discordant phylogenetic
relationships between 2019-nCoV and RaTG13 clade with their closest
partners, the Bat_SARS-like coronavirus sequences. In accordance with
previous analysis (http://virological.org/t/ncovs-relationship-to-bat-
coronaviruses-recombination-signals-no-snakes/331), Bat_SARS-like
coronavirus sequences cluster in different positions in the tree, sug-
gesting that they are recombinants, and thus that the 2019-nCoV and
RaTG13 are not (Ji et al., 2020;Magiorkinis et al., 2004). One previous
study based on codon usage analyses suggested that the spike protein of
2019-nCoV might have originated from one yet-unknown unsampled
coronavirus through recombination (Ji et al., 2020). Codon usage
analyses can resolve the origin of proteins with deep ancestry and in-
sufficient phylogenetic signal or invented de novo. The recently-pub-
lished bat coronavirus sequence however provides strong phylogenetic
information to resolve the origin of the Spike protein, as well as the rest
of the genome, suggesting a uniform ancestry across the genome. We
have previously shown that phylogenetic discordance in deep re-
lationships of coronaviruses is common and can be explained either by
ancient recombination event or altered evolutionary rates in different
lineages, or a combination of both (Magiorkinis et al., 2004). Our study
rejects the hypothesis of emergence as a result of a recent recombina-
tion event. Notably, the new coronavirus provides a new lineage for
almost half of its genome, with no close genetic relationships to other
viruses within the subgenus of sarbecovirus. This genomic part com-
prises half of the spike region encoding a multifunctional protein re-
sponsible also for virus entry into host cells (Babcock et al., 2004;Li
et al., 2005b). The unique genetic features of 2019-nCoV and their
potential association with virus characteristics and virulence in humans
remain to be elucidated.
Declaration of Competing Interest
All authors report no conflict of interest related to the submitted
work.
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Background: COVID-19, as a novel coronavirus disease caused by new coronavirus SARS-CoV-2, spreads all over the world, and brings harm to human in many countries. Humans suffered a lot from both SARS-CoV-2 now and by SARS-CoV in the year 2003. It is important to understand the differences and the relationships between these two types of viruses. Objective: To compare relative synonymous codon usage of ORF1ab gene in SARS-CoV-2 and SARS-CoV, relative synonymous codon usage of their genomes are studied in this paper from the bioinformatics perspective. Methods: The ORF1ab gene, which is an important non-structural polyprotein coding gene and now used for nucleic acid detection markers in many measurement method, in both SARS-CoV-2 (30 strains) and SARS-CoV (20 strains) are considered to be the research object in the present paper. The relative synonymous codon usage values of the ORF1ab gene are calculated to characterize the differences and the evolutionary characteristics among 50 strains. Results: There is a significant difference between SARS-CoV and SARS-CoV-2 when the relative synonymous codon usage value of ORF1ab genes is concerned. The results suggest that codon usage pattern of SARS-CoV is more similar to human than that of the SARS-CoV-2, and that the inner difference in SARS-CoV-2 strains is larger than that of SARS-CoV, which denote the larger diversity exits in the SARS-CoV-2 virus. Conclusion: These results show that the relative synonymous codon usage values in the coronavirus could be used for further research on their evolutionary phenomenon.
Application of Traditional Chinese Medicine and Systems Pharmacology in Drug Prevention and Treatment against COVID-19
Article
A novel coronavirus named SARS-CoV-2 is causing the severe acute pneumonia (COVID-19) and rapid spread nationally and internationally, resulting in a major global health emergency. Chinese governments and scientists have implemented a series of rigorous measures and scientific research to prevent and control the SARS-CoV-2 infection. However, there is still no specific antiviral drug or vaccine against SARS-CoV-2. It has been proven that traditional Chinese medicine (TCM) exerts an important role in the prevention and treatment of the COVID-19 caused by SARS-CoV-2 during the outbreak. Although the therapeutic effects of these TCM formulas are attractive, the molecular mechanism of action has not been fully elucidated. An emerging strategy of systems pharmacology has been proposed to be a promising method to interpret drug action in complex biological systems and quickly screen out the bioactive compounds from TCM to treat treatment of COVID-19 caused by SARS-CoV-2. Therefore, in this study, the epidemiology, TCM therapy, and the systems pharmacology-based method for TCM are reviewed for COVID-19 to provide a perspective for the prevention and treatment of SARS-CoV-2 infection. Further efforts should be made to reduce disease burden and improve the ability to design antiviral drugs and vaccines, which will benefit the health care system, economic development and even social stability.
Modeling analytics in COVID-19: prediction, prevention, control, and evaluation
Article
  • Jul 2021
The outbreak of COVID-19 has attracted attention from all around the world. Governments and institutions have adopted ways to fight COVID-19, but its prevalence is still strong. The SIR model has important reference value for the novel coronavirus epidemic, offering both preventive measures and the ability to predict future trends. Based on an analysis of the classical epidemiological SIR model along with key parameters, this paper aims to analyze the patterns of COVID-19, to discuss potential anti-COVID-19 measures, and to explain why we need to conduct appropriate measures against COVID-19. The use of the SIR model can play an important role in public health emergencies. Among the parameters of the SIR model, the contact ratio and the reproduction ratio are the factors that have the potential to mitigate the consequences of COVID-19. Anti-COVID-19 measures include wearing a mask, washing one’s hands, keeping social distance, and staying at home if possible.
ORIGINEA SARS-CoV-2 și RADIOGRAFIA PANDEMIEI CoVid-19. CIRCUMSTANȚE AGRAVANTE ȘI SEMNIFICAȚII SPIRITUALE. Inventar al cauzelor științifice și analiza teoriilor conspirației într-o abordare interdisciplinară.
Chapter
Full-text available
  • Jul 2021
1) Sunt prezentate succint cele mai importante pandemii din ultimul secol: gripele aviare sau porcine (A/H1N1, H2N2, H3N2, H5N1), SARS și MERS, precum și CoVid-19. (2) Sunt expuse câteva din posibilele cauze ale acestor pandemii (epidemiologice, ecologice sau antropologice): (ne)respectarea normelor de biosecuritate-în unitățile de creștere intensivă a mamiferelor și păsă-rilor, (insuficientele) reglementări privind piața animalelor sălbatice. Sunt detaliate 3 exemple: (liliecii-Rhinolophus ferrumequinum, civeta de palmier-Paradoxurus hermaphroditus, pangolinul (furnicarul solzos)-Manis javanica), și câteva practici abuzive legate de aceste mamifere. (3) Sunt evidențiate câteva dintre elementele care sprijină ipoteza originii naturale a pandemiilor, unele explicații care privesc liliecii ca "rezervoare naturale" de coronavirusuri și câteva cauze (culturale și civilizaționale) care contribuie astăzi la răspândirea rapidă a pandemiilor. (4) Este adusă în discuție ideea provenienței artificiale a virusului, răspândită repede la nivelul publicului larg cu ajutorul unor voci autorizate care s-au pronunțat în avans și fără dovezi temeinice. (5) Sunt introduse mențiuni privind posibilitatea provenienței naturale a SARS-CoV-2, despre explorări privind pre-zența pangolinului ca intermediar și despre adaptarea SARS-CoV-2 la receptorii celulelor umane. (6) Sunt adăugate observații științifice care sugerează posibilitatea originii artificiale a SARS- CoV-2: accidente de laborator din trecutul recent, care au expus populația unor agenți patogeni artificiali, procedee periculoase de cercetare genetică a virusurilor (rafinarea iterativă și mutațiile activante), unele particularități ale SARS-CoV-2 (adaptarea la receptorii ACE2 din celulele umane, situl de clivaj al furinei din proteina-spike), absența precursorilor, în mostrele prelevate din piețele animalelor sălbatice și cercetările existente la Institutul din Wuhan. (7) Sunt evidențiate motivele pentru care cercetarea științifică nu poate oferi acum răspunsuri clare despre originea noului virus (mutațiile rapide ale SARS-CoV-2 și absența unor date sigure privind primele cazuri de CoVid-19). Este evidențiat modul cum absența explicațiilor lasă un gol care este repede umplut de teoriile conspirației. (8) Prezint elementele care contribuie la răspândirea teoriilor conspirației. (9) Expun aspecte care privesc teoriile conspirației, aderența lor la nivelul publicului larg și în rândul specialiștilor. Sunt menționate câteva argumente menite să sprijine deosebirea conspirației (în genere, o acțiune secretă reală, care rămâne o vreme necunoscută publicului larg), de ceea ce reprezintă teoriile conspirației, ca ficțiuni falsificatoare. Sunt inventariate câteva din procesele psihologice sau sociale care contribuie la adoptarea rapidă a teoriilor conspirației (disonanța cognitivă, „paradoxul expertizei”, „oboseala cognitivă”, gândirea intuitivă, alte erori de percepție și evaluare). Sunt pomenite și unele remedii de ordin filosofic sau spiritual (epoche, spiritul critic, discernământul), precum și unele posibile valențe spirituale ale situării noastre în fața unui fapt real nedeslușit/ neînțeles (raportul credință vs credulitate, foamea de sens, „postul cognitiv”). Sunt evidențiate, în fine, unele efecte pe care teoriile conspirației le pot avea în plan social și spiritual, în raportul cetățe- nilor cu autoritățile, dar și în cadrul comunității de credință. (10) Menționez câteva înțelesuri spiri- tuale ale pandemiilor, oferite de antropologia patristică, având ca reper evenimentul căderii lui Adam și înțelesurile teologice ale suferinței și morții receptate deodată cu iubirea lui Dumnezeu. În legătură cu acestea, sunt aduse în discuție locuri din reflecția Sf. Ioan Damaschinul, Sf. Maxim Mărturisitorul și Dionisie Areopagitul. Sunt prezentate trei observații despre conduita creștinilor în timpul epidemiilor, desprinsă din poziția și observațiile Sf. Ciprian al Cartaginei față de epidemia de ciumă din secolul III. (11) Adaug considerații despre raționalitatea creației în lumina Întrupării Logosului și despre o raportare spirituală adecvată la lumea vie, la natura înconjurătoare, care decurg din ea, prin câteva observații formulate de teologi contemporani precum Panayotis Nellas, părintele Dumitru Stăniloae și Olivier Clement. Încercăm, prin acestea, o privire asupra civilizației actuale în oglinda înțelesurilor creștine despre lume și viață. Sunt identificate aici câteva din peri- colele ce amenință viitorul imediat al lumii (virusurile emergente, inechitățile sociale tot mai adânci, poluarea și risipa, supra-exploatarea resurselor, utilizarea abuzivă a tehnologiilor etc.) și necesitatea cultivării interiorității omenești, pentru (re)câștigarea dimensiunii spirituale a vieții, pentru o restructurare generală, rațională a civilizației. (Câteva secțiuni din acest text au apărut în volumul Pan-demon 2020 și Covid-19, Editura Sedcom Libris, Iași, 2020, pp. 51-94 și ulterior, într-o formă mai extinsă, în Revista Teologie și Viață, anul XXX (2020), nr. 1-4, 2020, pp: 57-137. DOI: https://doi.org/10.47433/tv.xcvn1-4.57. Față de acele versiuni, textul de față a suferit ample revizuiri și completări, unele secțiuni fiind reorganizate integral. A fost introdusă o secțiune nouă, care conține unele considerații științifice privind posibilitatea originii artificiale a virusului SARS-CoV-2, dar și o secțiune cu aspecte problematice privind receptarea unei pandemii de către creștini, petrecută în secolul al III-lea. Este vorba despre unui episod de ciumă înregistrat în Imperiul Roman. Revedem acest episod, situându-l în contextul pandemiei actuale, reluând poziția Sfântul Ciprian al Cartaginei față de unele nedumeriri ale creștinilor referitoare la epidemie. Regăsim unele elemente care ar putea schița o încadrare spirituală a pandemiei actuale și sugestii prețioase despre o posibilă receptare creștină a evenimentelor de acum. Față de ultima versiune a materialului, publicată în Revista Teologie și Viață, întinderea a fost dublată, fiind adăugate 60 de pagini.)
Metagenomic analysis of fecal and tissue samples from 18 endemic bat species in Switzerland revealed a diverse virus composition including potentially zoonotic viruses
Article
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Many recent disease outbreaks in humans had a zoonotic virus etiology. Bats in particular have been recognized as reservoirs to a large variety of viruses with the potential to cross-species transmission. In order to assess the risk of bats in Switzerland for such transmissions, we determined the virome of tissue and fecal samples of 14 native and 4 migrating bat species. In total, sequences belonging to 39 different virus families, 16 of which are known to infect vertebrates, were detected. Contigs of coronaviruses, adenoviruses, hepeviruses, rotaviruses A and H, and parvoviruses with potential zoonotic risk were characterized in more detail. Most interestingly, in a ground stool sample of a Vespertilio murinus colony an almost complete genome of a Middle East respiratory syndrome-related coronavirus (MERS-CoV) was detected by Next generation sequencing and confirmed by PCR. In conclusion, bats in Switzerland naturally harbour many different viruses. Metagenomic analyses of non-invasive samples like ground stool may support effective surveillance and early detection of viral zoonoses.
A Novel Coronavirus from Patients with Pneumonia in China, 2019
Article
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In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed another clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.).
The continuing epidemic threat of novel coronaviruses to global health - the latest novel coronavirus outbreak in Wuhang, China
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Origin and evolution of pathogenic coronaviruses
Article
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Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are two highly transmissible and pathogenic viruses that emerged in humans at the beginning of the 21st century. Both viruses likely originated in bats, and genetically diverse coronaviruses that are related to SARS-CoV and MERS-CoV were discovered in bats worldwide. In this Review, we summarize the current knowledge on the origin and evolution of these two pathogenic coronaviruses and discuss their receptor usage; we also highlight the diversity and potential of spillover of bat-borne coronaviruses, as evidenced by the recent spillover of swine acute diarrhoea syndrome coronavirus (SADS-CoV) to pigs.
RDP4: Detection and analysis of recombination patterns in virus genomes
Article
Full-text available
  • Mar 2015
RDP4 is the latest version of recombination detection program (RDP), a Windows computer program that implements an extensive array of methods for detecting and visualising recombination in, and stripping evidence of recombination from, virus genome sequence alignments. RDP4 is capable of analysing twice as many sequences (up to 2,500) that are up to three times longer (up to 10 Mb) than those that could be analysed by older versions of the program. RDP4 is therefore also applicable to the analysis of bacterial full-genome sequence datasets. Other novelties in RDP4 include (1) the capacity to differentiate between recombination and genome segment reassortment, (2) the estimation of recombination breakpoint confidence intervals, (3) a variety of ‘recombination aware’ phylogenetic tree construction and comparison tools, (4) new matrix-based visualisation tools for examining both individual recombination events and the overall phylogenetic impacts of multiple recombination events and (5) new tests to detect the influences of gene arrangements, encoded protein structure, nucleic acid secondary structure, nucleotide composition, and nucleotide diversity on recombination breakpoint patterns. The key feature of RDP4 that differentiates it from other recombination detection tools is its flexibility. It can be run either in fully automated mode from the command line interface or with a graphically rich user interface that enables detailed exploration of both individual recombination events and overall recombination patterns.
Another Decade, Another Coronavirus
Article
Coronavirus Infections—More Than Just the Common Cold
Article
Homologous recombination within the spike glycoprotein of the newly identified coronavirus may boost cross‐species transmission from snake to human
Article
The current outbreak of viral pneumonia in the city of Wuhan, China, was caused by a novel coronavirus designated 2019‐nCoV by the World Health Organization, as determined by sequencing the viral RNA genome. Many initial patients were exposed to wildlife animals at the Huanan seafood wholesale market, where poultry, snake, bats, and other farm animals were also sold. To investigate possible virus reservoir, we have carried out comprehensive sequence analysis and comparison in conjunction with relative synonymous codon usage (RSCU) bias among different animal species based on the 2019‐nCoV sequence. Results obtained from our analyses suggest that the 2019‐nCoV may appear to be a recombinant virus between the bat coronavirus and an origin‐unknown coronavirus. The recombination may occurred within the viral spike glycoprotein, which recognizes a cell surface receptor. Additionally, our findings suggest that 2019‐nCoV has most similar genetic information with bat coronovirus and most similar codon usage bias with snake. Taken together, our results suggest that homologous recombination may occur and contribute to the 2019‐nCoV cross‐species transmission. Research Highlights • Taken together, our results suggest that homologous recombination may occur and contribute to the 2019‐nCoV cross‐species transmission.
Molecular Evolutionary Genetics Analysis (MEGA) for macOS
Article
The Molecular Evolutionary Genetics Analysis (MEGA) software enables comparative analysis of molecular sequences in phylogenetics and evolutionary medicine. Here, we introduce the macOS version of the MEGA software. This new version eliminates the need for virtualization and emulation programs previously required to use MEGA on Apple computers. MEGA for macOS utilizes memory and computing resources efficiently for conducting evolutionary analyses on Apple computers. It has a native Cocoa graphical user interface that is programmed to provide a consistent user experience across macOS, Windows, and Linux. MEGA for macOS is available from www.megasoftware.net free of charge.
Coronavirus as a Possible Cause of Severe Acute Respiratory Syndrome
Article
  • Jan 2003
Middle East respiratory syndrome coronavirus infection in dromedary camels in Saudi Arabia
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  • Jan 2014
The Middle East respiratory syndrome (MERS) is proposed to be a zoonotic disease; however, the reservoir and mechanism for transmission of the causative agent, the MERS coronavirus, are unknown. Dromedary camels have been implicated through reports that some victims have been exposed to camels, camels in areas where the disease has emerged have antibodies to the virus, and viral sequences have been recovered from camels in association with outbreaks of the disease among humans. Nonetheless, whether camels mediate transmission to humans is unresolved. Here we provide evidence from a geographic and temporal survey of camels in the Kingdom of Saudi Arabia that MERS coronaviruses have been circulating in camels since at least 1992, are distributed countrywide, and can be phylogenetically classified into clades that correlate with outbreaks of the disease among humans. We found no evidence of infection in domestic sheep or domestic goats.