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Discussion - 2019-nCoV genetics

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  • #16
    I have a question - how much reassortment / recombination goes on between CoV viruses of different clades. For example if 2019 nCoV meets MERS, is there a risk of reassortment?


    • #17
      des lieux ou des porcs et des humains cohabitent en Chine cela me semble exister d'une part , d'autre part on ne sait rien de ce qui se passe sur les porcs sauvages chinois , donc les sangliers ...


      • #18
        Mining coronavirus genomes for clues to the outbreak’s origins

        By Jon CohenJan. 31, 2020 , 6:20 PM
        “One of the biggest takeaway messages [from the viral sequences] is that there was a single introduction into humans and then human-to-human spread,” says Trevor Bedford, a bioinformatics specialist at the University of Washington and Fred Hutchinson Cancer Research Center.
        The longer a virus circulates in a human populations, the more time it has to develop mutations that differentiate strains in infected people, and given that the 2019-nCoV sequences analyzed to date differ from each other by seven nucleotides at most, this suggests it jumped into humans very recently. But it remains a mystery which animal spread the virus to humans.
        According to Xinhua, the state-run news agency, “environmental sampling” of the Wuhan seafood market has found evidence of 2019-nCoV. Of the 585 samples tested, 33 were positive for 2019-nCoV and all were in the huge market’s western portion, which is where wildlife were sold. “The positive tests from the wet market are hugely important,” says Edward Holmes, an evolutionary biologist at the University of Sydney ...
        Yet there have been no preprints or official scientific reports on the sampling, so it’s not clear which, if any, animals tested positive. “Until you consistently isolate the virus out of a single species, it’s really, really difficult to try and determine what the natural host is,” says Kristian Andersen, an evolutionary biologist at Scripps Research.
        It’s not just a “curious interest” to figure out what sparked the current outbreak, Daszak says. “If we don't find the origin, it could still be a raging infection at a farm somewhere, and once this outbreak dies, there could be a continued spillover that’s really hard to stop. But the jury is still out on what the real origins of this are.”


        • #19
          Originally posted by Vibrant62 View Post
          I have a question - how much reassortment / recombination goes on between CoV viruses of different clades. For example if 2019 nCoV meets MERS, is there a risk of reassortment?
          Yeah, I'd think that's one of the real dangers. Because MERS is much more severe, and you might get a resultant virus that spreads as easily as 2019 nCoV but has the severity of MERS.

          I'm also concerned about what happens if someone gets co-infected with 2019 nCoV and one of the four seasonal human coronaviruses, which seems more likely than a MERS co-infection.


          • #20
            L'un des probl?mes me semble que lors de la fermeture des proc?dures judiciaires ont du ?tre ouvertes. Je crains que certains ?levages ou fournisseurs d'animaux interdits ont alimente x lieux. En revanche, je suis s?r qu'ils cherchent et vu leurs comp?tences, ils vont trouver. Pour faire entrevoir de fa?on imag?e, le dossier march? global, en Chine, c'est comme celui de la vente d'arme au U. S. A. En tout cas entre le dossier peste porcine africaine et celui ci cela doit ?tre lourd... Ils doivent ?tre f?licit?s et non critiques, de mon point de vue... Mais apr?s la phase de crise, il faudra vraiment trai


            • #21
              Originally posted by bertrand789 View Post
              La m?me source a produit aussi ceci :
              Here's What Makes Coronavirus and African Swine Fever Different

              Jennifer Shike
              January 31, 2020 12:40 PM
              Saif says the best examples of CoV that infect the gut and cause diarrhea and deaths in pigs are porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus that first emerged in the U.S. in 2013-14. Both are still present in pigs.

              These viruses are members of two different groups of coronaviruses – alpha and delta CoV. Saif explains they are genetically distinct and do not cross-protect against one another. 2019-nCoV is part of a third distinct group of coronaviruses (beta CoV) and is genetically and antigenically distinct from these two swine coronaviruses, she adds.
              Could 2019-nCoV Impact the Swine Industry?

              There is no evidence from China that 2019-nCoV came from pigs or even that it could infect pigs, Saif says. In addition, there was no previous data that the related SARS CoV infected pigs.


              • #22
                Le virus de la peste porcine africaine me semble un virus d'une tique qui d?sormais se multiplie sur animaux ? sang chaud. Il pose des probl?mes car il impose des changements zoo techniques pas simple ? mettre en œuvre... On a expliqu? les pourquoi ou comment, de sa survenue ?

                S'il est envisage, que pour le coronavirus de chauve souris, pour par mutation il faudrait 65 ans pour arriver ? celui ?voqu?, je suis surpris qu'en 65 ans, rien n'ai ?t? vu. En tout cas, pour celui qui atteint les porcelets, donc Hku2, on a expliqu? les pourquoi ou comment de sa survenue ?


                • #23
                  >An outbreak of respiratory illness caused by a novel coronavirus (nCoV-2019, NC_045512.2 40)
                  >first identified in Wuhan China has resulted in over seven thousand confirmed cases.
                  >So far, the nCoV-2019 has been reported to share 96% sequence identity to the RaTG13 genome
                  >(EPI_ISL_402131). However, the S1 Receptor Binding Domain (RBD) of the nCoV-2019 genome
                  >was noticeably divergent between the two at amino acid residues 350 to 550 – Figure 1A.
                  >We aimed to identity coronaviruses related to nCoV-2019 in viral metagenomics datasets
                  >available in the public domain. In a recently published dataset describing viral diversity in
                  >Malayan pangolins (PRJNA573298 87) we used VirMAP 38 to reconstruct a coronavirus genome
                  >(approximately 84% complete from samples SRR10168377 33 and SRR10168378 20) that
                  >shared 97% amino acid identity across the same RBD segment – Figure 1B. This result
                  i>ndicates a potential recombination event for nCoV-2019.
                  >Edit -
                  >From the coordinates shown in this preprint 121 (Figure 4), it looks like most of the differences between RaTG13 >and nCoV-2019 are restricted to loop 2 of the receptor binding motif (positions ~450-500).

                  > t seems unlikely that the receptor binding domain–and especially the receptor binding motif–would be nearly identical to one
                  > found in pangolin through random chance.
                  > incidentally, pangolins were sold in the market at the center of all of this 119.
                  I'm interested in expert panflu damage estimates
                  my current links: ILI-charts:


                  • #24
                    > The 2013 Yunnan bat virus genome sequence {"RaTG13"} is now available
                    > from GenBank with accession number MN996532 15.

                    Last edited by gsgs; February 6, 2020, 04:14 AM.
                    I'm interested in expert panflu damage estimates
                    my current links: ILI-charts:


                    • #25
                      Comme ? chaque fois, la situation s'inverse, car, d?sormais, ce sont des humains qui peuvent contaminer des populations d'animaux, peut ?tre, d?j? porteuses d'autres coronavirus. Qui va se charger de suivre cela ? C'est du domaine des instances m?dicales ?

                      Pour ?tre concret et pr?cis , si la Chine fait un ?norme travail ? f?liciter , il y a des zones d'ombres, vu son organisation interne, en ?volution continue. Pour un autre dossier, celui de la peste porcine africaine, on ne sait rien de ce qui se passe dans ses populations de sangliers et ou de porcs sauvages, ni de sa strat?gie pour ce sujet . Il y a peut ?tre des essais de vaccins plus ou plus volontaire en cours, par exemple .

                      Mais les autres font vraiment mieux ?
                      On se sait pas, non plus, grand chose, officiellement, sur les influenzas des populations de dindes sauvages aux U.S.A .

                      Ce dossier a un m?rite, il a eu et va avoir un co?t tel, que tous les pays vont devoir mieux faire. Parler des ?volutions envisag?es, me semble une fa?on de restaurer la confiance, mise ? mal, ? chaque crise, par la mise en lumi?re des failles des modes organisationnels en place...


                      • #26
                        Here's an opinion that RaTG13 is not the proximal source:

                        I have been privately dealing with rumors and inquiries, focused on the RRAR potential furin cleavage site, that nCoV2019 may have a suspicious origin as an engineered, laboratory-generated virus either accidentally or deliberately released in the area of the Wuhan seafood and animal market. The publication of the highly similar RaTG13 sequence about a week ago has fueled this type of speculation. As I have told people privately, I see no evidence at all to support such a claim. In sharp contra...

                        Ask Congress to Investigate COVID Origins and Government Response to Pandemic.

                        i love myself. the quietest. simplest. most powerful. revolution ever. ---- nayyirah waheed

                        "...there’s an obvious contest that’s happening between different sectors of the colonial ruling class in this country. And they would, if they could, lump us into their beef, their struggle." ---- Omali Yeshitela, African People’s Socialist Party

                        (My posts are not intended as advice or professional assessments of any kind.)
                        Never forget Excalibur.


                        • #27
                          > he TMRCA of the two sequences nCoV2019 and RaTG13 of 69.5 years ago – roughly 1950 +/- 10 years or so.

                          that's surprising, given that the others are even much more distant

                          I'm not familiar with coronaviruses ...if it were avian flu, I'd calculate ~6years for 96.5% identity

                          They have probably calculated the mutation rate in the current outbreak ... maybe I can find it


                          > Coalescent model Estimated rate 95% interval
                          > Constant size 1.21x10^-3 0.60x10^-3 – 1.96x10^-3
                          > Exponential growth 9.81x10^-3 0.25x10^-3 – 1.59x10^-3
                          > Table 1 | The estimated rate of evolution (substitutions per site per year) of the sampled nCoV-2019 genomes.

                          so let's say 1*10^-3 mutations per nucleotide position per year
                          or 30 mutations per year on the 30000-nucleotides-genome.
                          That would be ~1/3 of the flu-rate, so my 6 years above grow to 18.
                          No way to get 69.5 years

                          I'm puzzled about all the hills and valleys in the mutation-pictures, are these all
                          due to recombinations ?
                          I'm interested in expert panflu damage estimates
                          my current links: ILI-charts:


                          • #28
                            gs if you use the nextstrain link and set the 'tree type' to clock and the 'divergence/time' button to time it will give you the calculated rate for the GISAID data set currently it reads 27.817 subs/y


                            • #29
                              The current TWIV is very good, it is 1 hour on SARS-CoV-2 with Vincent, an American Infectious disease specialist and an Italian researcher working in Switzerland. The researchers team are testing a nano-particle with common viral receptors on their surfaces as a viral 'fly-paper' with some success on a wide range of viruses inc. SARS-CoV-2. This is at a very early stage and they have not even verified their first test yet so it is unlikely to help this time round. Wouldn't it have been nice to have a useful broadly acting anti-viral before, rather than after, this sort of thing happened? (note: rhetorical)

                              Donate to MicrobeTV Featured Episode TWiV reviews the potential impact on science of the Supreme Court ruling in the Chevron decision, measles in New Hampshire and Vermont, new who proposed terminology for respiratory pathogen transmission, and pathogenicity and transmission of bovine H5N1 influenza virus. Hosts: Vincent Racaniello, Dickson Despommier, and Rich Condit More TWiV episodes More
                              Last edited by JJackson; March 8, 2020, 08:59 AM.


                              • #30
                                Regarding the mysterious sequence RaTG13, I got from another blog the hint that I should look closer at the sequence KP876546 that is cited in the article:
                                Ge, X., Wang, N., Zhang, W. et al. Coexistence of multiple coronaviruses in several bat colonies in an abandoned mineshaft. Virol. Sin. 31, 31–40 (2016).

                                The sequence KP876546 in NCBI is very short (only 370 bp) and is defined as Rhinolophus bat coronavirus BtCoV/4991 partial RNA-dependent RNA polymerase. This sequence is also analysed in the article Characterization of a New Member of Alphacoronavirus with Unique Genomic Features in Rhinolophus Bats

                                I blasted the KP876546 sequence in NCBI and I got 100% identities with RaTG13 and 99% identities with MT039890 Severe acute respiratory syndrome coronavirus 2 isolate SNU01, complete genome (South Korea). Next closer sequence not from SARS-CoV2 is the pangolin sequence MT084071.
                                To my opinion the sequence KP876546 could be the first evidence of the RaTG13 sequence or a sequence even closer to SARs-CoV2. In Ge et al., it is stated that the 370 bp sequence was prolonged of 816 bp and the spike protein was sequenced but this information for this sample has been not made public.

                                I have found a publication on the comparison of KP876546 with SARS-CoV2 before that RaTG13 was submitted to NCBI:

                                Liangjun Chen, Weiyong Liu, Qi Zhang, Ke Xu, Guangming Ye, Weichen Wu, Ziyong Sun, Fang Liu, Kailang Wu, Bo Zhong, Yi Mei, Wenxia Zhang, Yu Chen, Yirong Li, Mang Shi, Ke Lan & Yingle Liu (2020) RNA based mNGS approach identifies a novel human coronavirus from two individual pneumonia cases in 2019 Wuhan outbreak, Emerging Microbes & Infections, 9:1, 313-319, DOI: 10.1080/22221751.2020.1725399

                                The author writes that: “further sequencing of the corresponding PCR product (from SARS-CoV2) surprisingly suggested that the virus discovered is more closely related to BtCoV/4991” (KP876546) “(97.35%) but not SARS-CoV. The genomes of the 2019-nCoV were further analysed to determine its origin and evolutionary history. Full genome comparisons indicated that 2019-nCoV is close to CoVs circulating in Rhinolophus (Horseshoe bats). For example, it shared 98.7% nucleotide identity to bat coronavirus strain BtCoV/4991 (GenBank KP876546, only 370 nt sequence of RdRp gene) and 87.9% nucleotide identity to bat CoV strain bat-SLCoVZC45 and bat-SL-CoVZXC21, indicating that it was quite divergent from the currently known human CoV, including SARS-CoV (79.7%). The close relationship with BtCoV/4991 is quite essential in tracing the potential reservoir host of 2019-nCoV. Unfortunately, the BtCoV/4991 sequence was only partial (373bp in length) and thus no comparisons can be made for the rest of genomes.”

                                In the article:
                                Zhou, P., Yang, X., Wang, X. et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579, 270–273 (2020).

                                where for the first time RaTg13 appears, it is written:

                                “We then found a short RdRp region from a bat coronavirus termed BatCoV RaTG13 which we previously detected in Rhinolophus affinis from Yunnan Province showed high sequence identity to nCoV-2019. We did full-length sequencing to this RNA sample. Simplot analysis showed that nCoV-2019 was highly similar throughout the genome to RaTG13, with 96.2% overall genome sequence identity.”

                                Interestingly, the article of Ge et al. is not part of the bibliography of this work. To my opinion further sequencing of KP876546 was so interesting that the results were kept secret and manipulations of this virus was carried over until the outbreak of SARS-CoV2.