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lördag 8 februari 2020

Tarkistan uudet tiedot nCoV-2019 genomista: 5 vastausta. Onko jotain uutta esim jokin "W1/W2"

 Käytän tuota  kooditermiä "w1/w2"- etsiessäni  mahdollista uutta mutaatiota tai virulenssitekijää.Löytyyhän sitä:  Uusi wuhanilainen lisägeeni  ORF3b ja uusi ORF8.  Myös  RBD:ssä muutosta  S-piikissä. Myös jotain  muutosta NC:ssä. kaikkien mielstä riittvästi eroja muihin, jota tämä voidaan sanoa kokonaan uudeksi virukseksi maapallolla.

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Items: 5

1.  Seitsemän nsp- virusproteiinin  kontrollin mukaan  uusi virus on SARSr-CoV tyyppiä ja sen reseptori on ACE2.

Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CL, Chen HD, Chen J, Luo Y, Guo H, Jiang RD, Liu MQ, Chen Y, Shen XR, Wang X, Zheng XS, Zhao K, Chen QJ, Deng F, Liu LL, Yan B, Zhan FX, Wang YY, Xiao GF, Shi ZL.
Nature. 2020 Feb 3. doi: 10.1038/s41586-020-2012-7. [Epub ahead of print]
Since the SARS outbreak 18 years ago, a large number of severe acute respiratory syndrome-related coronaviruses (SARSr-CoV) have been discovered in their natural reservoir host, bats1-4. Previous studies indicated that some of those bat SARSr-CoVs have the potential to infect humans5-7. Here we report the identification and characterization of a novel coronavirus (2019-nCoV) which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started from 12 December 2019, has caused 2,050 laboratory-confirmed infections with 56 fatal cases by 26 January 2020. Full-length genome sequences were obtained from five patients at the early stage of the outbreak. They are almost identical to each other and share 79.5% sequence identify to SARS-CoV. Furthermore, it was found that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. The pairwise protein sequence analysis of seven conserved non-structural proteins (nsps) show that this virus belongs to the species of SARSr-CoV. The 2019-nCoV virus was then isolated from the bronchoalveolar lavage fluid of a critically ill patient, which can be neutralized by sera from several patients. Importantly, we have confirmed that this novel CoV uses the same cell entry receptor, ACE2, as SARS-CoV.
2.     (Toistan tämän sitaatin)
Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, Wang W, Song H, Huang B, Zhu N, Bi Y, Ma X, Zhan F, Wang L, Hu T, Zhou H, Hu Z, Zhou W, Zhao L, Chen J, Meng Y, Wang J, Lin Y, Yuan J, Xie Z, Ma J, Liu WJ, Wang D, Xu W, Holmes EC, Gao GF, Wu G, Chen W, Shi W, Tan W.
Lancet. 2020 Jan 30. pii: S0140-6736(20)30251-8. doi: 10.1016/S0140-6736(20)30251-8. [Epub ahead of print]
The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues.
3.
Lu H.
Biosci Trends. 2020 Jan 28. doi: 10.5582/bst.2020.01020. [Epub ahead of print]
As of January 22, 2020, a total of 571 cases of the 2019-new coronavirus (2019-nCoV) have been reported in 25 provinces (districts and cities) in China. At present, there is no vaccine or antiviral treatment for human and animal coronavirus, so that identifying the drug treatment options as soon as possible is critical for the response to the 2019-nCoV outbreak. Three general methods, which include existing broad-spectrum antiviral drugs using standard assays, screening of a chemical library containing many existing compounds or databases, and the redevelopment of new specific drugs based on the genome and biophysical understanding of individual coronaviruses, are used to discover the potential antiviral treatment of human pathogen coronavirus.
 Lopinavir /Ritonavir, 
Nucleoside analogues,
 Neuraminidase inhibitors, 
 Remdesivir, peptide (EK1), arbidol, 
RNA synthesis inhibitors (such as TDF, 3TC),
 anti-inflammatory drugs (such as hormones and other molecules),
 Chinese traditional medicine, such ShuFengJieDu Capsules and Lianhuaqingwen Capsule, could be the drug treatment options for 2019-nCoV
However, the efficacy and safety of these drugs for 2019- nCoV still need to be further confirmed by clinical experiments.Free Article
4.
Benvenuto D, Giovanetti M, Ciccozzi A, Spoto S, Angeletti S, Ciccozzi M.
J Med Virol. 2020 Jan 29. doi: 10.1002/jmv.25688. [Epub ahead of print]
There is a worldwide concern about the new coronavirus 2019-nCoV as a global public health threat. In this article, we provide a preliminary evolutionary and molecular epidemiological analysis of this new virus. A phylogenetic tree has been built using the 15 available whole genome sequences of 2019-nCoV, 12 whole genome sequences of 2019-nCoV, and 12 highly similar whole genome sequences available in gene bank (five from the severe acute respiratory syndrome, two from Middle East respiratory syndrome, and five from bat SARS-like coronavirus). Fast unconstrained Bayesian approximation analysis shows that the nucleocapsid (NC) and the spike (S) glycoprotein have some sites under positive pressure, whereas homology modeling revealed some molecular and structural differences between the viruses. The phylogenetic tree showed that 2019-nCoV significantly clustered with bat SARS-like coronavirus sequence isolated in 2015, whereas structural analysis revealed mutation in Spike Glycoprotein and nucleocapsid protein. From these results, the new 2019-nCoV is distinct from SARS virus, probably transmitted from bats after mutation conferring ability to infect humans.
5. Näyttää siltä, että jo joulukuussa oli havaittu tässä mysteerisessä, atyyppistä pneumoniaa aiheutavassa koronaviruksessa  genomista  uutta lisää.  Accessory proteins, subgenomiset lisät  ORF3b  ja  uusi ORF8 ORF3b koodasi jotain aivan uutta lyhyttä proteiinia. Lisäksi uusi ORF8  todennäköisesti koodasi erittynyttä sekreettiproteiinia, josa oli alfahelix ja sitä seuraava beetatuppi, jossa kuusi säiettä.

( näitä mainintoja en ole nähnyt muissa artikkeleissa ennen tai jälikeen joulukuun).

Chan JF, Kok KH, Zhu Z, Chu H, To KK, Yuan S, Yuen KY.
Emerg Microbes Infect. 2020 Dec;9(1):221-236. doi: 10.1080/22221751.2020.1719902.
A mysterious outbreak of atypical pneumonia in late 2019 was traced to a seafood wholesale market in Wuhan of China. Within a few weeks, a novel coronavirus tentatively named as 2019 novel coronavirus (2019-nCoV) was announced by the World Health Organization. We performed bioinformatics analysis on a virus genome from a patient with 2019-nCoV infection and compared it with other related coronavirus genomes. Overall, the genome of 2019-nCoV has 89% nucleotide identity with bat SARS-like-CoVZXC21 and 82% with that of human SARS-CoV. The phylogenetic trees of their orf1a/b, Spike, Envelope, Membrane and Nucleoprotein also clustered closely with those of the bat, civet and human SARS coronaviruses. However, the external subdomain of Spike's receptor binding domain(RBD) of 2019-nCoV shares only 40% amino acid identity with other SARS-related coronaviruses.  Remarkably, its orf3b encodes a completely novel short protein. Furthermore, its new orf8 likely encodes a secreted protein with an alpha-helix, following with a beta-sheet(s) containing six strands. Learning from the roles of civet in SARS and camel in MERS, hunting for the animal source of 2019-nCoV and its more ancestral virus would be important for understanding the origin and evolution of this novel lineage B betacoronavirus. These findings provide the basis for starting further studies on the pathogenesis, and optimizing the design of diagnostic, antiviral and vaccination strategies for this emerging infection.
Free Article

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