C*I
发帖数: 4736 | 1 lubbock34，又名“胡汉三又回来了”，从名字判断，其年龄在53岁以上，职业应当是
个5毛。因为其马甲连续系列被多少穿戴使用，难说不是个5毛团伙。
最近这些天，lubbock一直拼命宣传病毒不是武汉所泄露出来的，明说暗示可能是美国
人投的毒。因此，刻意从bioRxiv上找来了一个matthew wong的未经正式发表preprint
的paper来佐证。说蝙蝠病毒不是新冠状病毒的initial病毒，穿山甲所带的冠状病毒才
是这次武汉病毒的原始宿主。为此，接二连三的在买买提开贴，带领一帮大小男女五毛
，乎着号子制造舆论风潮，误导视听，百般为病毒所解脱。
既然lubbock过来过去都是这个什么马来西亚人matthew wong的论文，那我们就看看这
matthew wong到底是个什么人物了。
按照bioRxiv的公开介绍，这watthew wong，只是一个大学本科/bs的学生，既没有硕士
学位，也不是phd candidate, 而是在 Alkek Center for Metagenomics and
Microbiome Research, Department of Molecular Virology and Microbiology,
Baylor College of Medicine上学或者工作。
至于他对新冠病毒的研究，可以说屁都不懂，因为他和其它几个医学院做cancer教学和
研究的phd合作发表的那个所谓穿山甲/pangolins possibly indicating a more
complex origin for nCoV-2019. 其实压根就是google了GenBank 数据库，比对了一下
别人所做的相关资料后，得出的一个很不周延的假设性推理而已。用他们自己的话说，
他们并没有做任何实验研究，也就是连穿山甲的毛都没有摸过，而是Data used in the
study which based on the Viral metagenomic datasets of hosts that could
potentially harbor coronaviruses were downloaded from the NCBI BioProject
database. These included PRJNA5732983 (pangolin), PRJNA597258 (fruit bats)
and PRJNA379515 (bats). The coronavirus genome (recovered from bat, GenBank
accession number MG772933.16) reported to be the most homologous to the nCoV
-2019 outbreak strain prior to the publication the RaTG13 (GenBank accession
number MN996532) was also downloaded.
有意思的是，在纸上谈兵的coronavirus genomes 对比中，可资对比的只有Two
samples in this dataset yielded two partial coronavirus genomes that
overlapped >8.4kb at >99% nucleotide identity with each other，The multiple
alignments across the RBM segments revealed an 89% nucleotide (Figure 1B)
and 98% amino acid identity (Figure 1C) of the Pangolin-CoV compared to nCoV
-2019.
也就是说，在众多的genomes对比中，其实可用做对比的只有2个samples当中的2个
partial segments 和新冠状病毒genomes有99%的相似度。 另外可供对比的一个是98%
， 另一个是89%。 其它GenBank 没有info可用做比对的，就没办法做和不知道结果了
。
Themultiple alignments across the RBM segments revealed an 89% nucleotide (
Figure 1B) and 98% amino acid identity (Figure 1C) of the Pangolin-CoV
compared to nCoV-2019.
由于只能在基因库中找到很少的资料用作对比，更没有第一手的实验结果数据和资料来
证实，写的这个没有公开发表的paper压根没有说服力。他们自己也没有底气，只好毫
不掩饰的说这只是把我们的看法提出来让大家讨论/discussion. 对此，他们最后还特
别强调：
The main limitations of this analysis are the lack of additional viral
datasets arising from pangolins or the availability of coronavirus genomes
isolated from pangolins that could be used for multiple genome alignments
with nCoV-2019.
他们（写这个文章）最大的局限性是既没有（看见过）穿山甲身上的病毒，也没有（看
见）新冠状病毒的病毒。 （其实就是google了被人放到GenBank里面的资料后，胡拉被
子乱扯毯子，纸上谈兵的，看起来还蛮老是的，比Lubbock厚道了很多）。
In addition,the current analysis only focuses on the spike protein of
nCoV-2019 without
exploring additional recombination events that may lead to changes in
hose tropism. Nonetheless,the identification of a possible recombination
event in the host-receptor binding protein of nCoV-2019, suggesting
an intermediate host, supports a call for continuous surveillance of
species known to be infected by this group of viruses, including
pangolins, as well as all small mammals sold in such wet markets as
the Huanan Seafood Wholesale Market in Wuhan to better understand and
characterize zoonotic transmission events.
另外，他们还承认，他们只比对了nCov-2019冠状病毒中的Spike protein/s 蛋白。其
它压根没有，也根本没有涉及到。
所以，lobbock 说这个所谓的论文证实了武汉新冠状病毒来自穿山甲，实在扯蛋，无耻
，无知得令人咂舌！ 而且更缺德得引申并造摇说matthew wong 发现了4个神秘的氨基
酸PRRA，简直就是信口雌黄，胡说八道！
下面的链接是paper原文，你们自己看吧！看看这个没有做任何相关实验，没有见过穿
山甲病毒，更没有看见过新冠状病毒的本科生matthew wong，发现的所谓4个神秘的氨
基酸PRRA到底在哪里！
麻痹的，我真是被五毛的造摇干劲和精神震撼了！
https://www.biorxiv.org/content/10.1101/2020.02.07.939207v1.full.pdf | k**********4
发帖数: 16092 | 2 我看你一直认为搞基因组研究要拿到材料，一直强调Wong没摸过山甲，其实不是这样的
，从已经发表的基因序列就可以比较，不一定自己要从测一遍
preprint
【在 C*I 的大作中提到】
: lubbock34，又名“胡汉三又回来了”，从名字判断，其年龄在53岁以上，职业应当是
: 个5毛。因为其马甲连续系列被多少穿戴使用，难说不是个5毛团伙。
: 最近这些天，lubbock一直拼命宣传病毒不是武汉所泄露出来的，明说暗示可能是美国
: 人投的毒。因此，刻意从bioRxiv上找来了一个matthew wong的未经正式发表preprint
: 的paper来佐证。说蝙蝠病毒不是新冠状病毒的initial病毒，穿山甲所带的冠状病毒才
: 是这次武汉病毒的原始宿主。为此，接二连三的在买买提开贴，带领一帮大小男女五毛
: ，乎着号子制造舆论风潮，误导视听，百般为病毒所解脱。
: 既然lubbock过来过去都是这个什么马来西亚人matthew wong的论文，那我们就看看这
: matthew wong到底是个什么人物了。
: 按照bioRxiv的公开介绍，这watthew wong，只是一个大学本科/bs的学生，既没有硕士
| i*****9
发帖数: 698 | 3 如果是美国投毒，习总要号召加强战备，而不是生物安全。 | C*I
发帖数: 4736 | 4 相比较而言，石正丽的《Bat origin of human coronaviruses/蝙蝠是人类冠状病毒的
来源》是扎扎实实的抓蝙蝠，解剖蝙蝠，分离病毒，对比DNA,RNA后得出得结论。
请lobbock读一读，说一说，走两步！
http://virologyj.biomedcentral.com/articles/10.1186/s12985-015-0422-1
Review
Open Access
Published: 22 December 2015
Bat origin of human coronaviruses
Ben Hu, Xingyi Ge, Lin-Fa Wang & Zhengli Shi
Virology Journal volume 12, Article number: 221 (2015) Cite this article
Abstract
Bats have been recognized as the natural reservoirs of a large variety of
viruses. Special attention has been paid to bat coronaviruses as the two
emerging coronaviruses which have caused unexpected human disease outbreaks
in the 21st century, Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV
) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV), are suggested
to be originated from bats. Various species of horseshoe bats in China have
been found to harbor genetically diverse SARS-like coronaviruses. Some
strains are highly similar to SARS-CoV even in the spike protein and are
able to use the same receptor as SARS-CoV for cell entry. On the other hand,
diverse coronaviruses phylogenetically related to MERS-CoV have been
discovered worldwide in a wide range of bat species, some of which can be
classified to the same coronavirus species as MERS-CoV. Coronaviruses
genetically related to human coronavirus 229E and NL63 have been detected in
bats as well. Moreover, intermediate hosts are believed to play an
important role in the transmission and emergence of these coronaviruses from
bats to humans. Understanding the bat origin of human coronaviruses is
helpful for the prediction and prevention of another pandemic emergence in
the future.
Background
Bats, with extensive geographical distribution and capability of flight,
constitute the second largest group of mammalian species and have been
documented as natural hosts of a large number of diverse viruses such as
lyssaviruses, paramyxoviruses and filoviruses [1, 2]. In the past decade,
numerous novel coronaviruses have been discovered in a wide variety of bat
species throughout Asia, Europe, Africa and America [3]. Within the
coronavirus genera Alphacoronavirus and Betacoronavirus, which mainly infect
mammals, 7 out of the 15 currently assigned viral species have only been
found in bats [4]. It is proposed that bats are major hosts for
alphacoronaviruses and betacoronaviruses and play an important role as the
gene source in the evolution of these two coronavirus genera [5]. Among the
coronaviruses harbored by bats, some have drawn particular research
interests, as they have been found to be associated with two high profile
human disease outbreaks, Severe Acute Respiratory Syndrome (SARS) and Middle
East Respiratory Syndrome (MERS).
In this review, we focus on the emerging coronaviruses putatively linked to
a zoonotic origin from bats, represented by SARS coronavirus (SARS-CoV) and
MERS coronavirus (MERS-CoV). We present an overview of current evidence for
bat origin of these two viruses and also discuss how the spillover events of
coronavirus from animals to humans may have happened. Considering that bats
have been known to harbor more coronaviruses than any other species, it is
likely that SARS-CoV and MERS-CoV won’t be the only bat coronaviruses to
jump among species and cause human infections. Bat coronaviruses should be
seriously regarded in light of their potential risks to public health.
Emergence of SARS and MERS
SARS first emerged in late 2002 in Guangdong Province, southern China, as a
novel clinical severe disease (termed “atypical pneumonia”) marked by
fever, headache and subsequent onset of respiratory symptoms including cough
, dyspnea and pneumonia. Being highly transmissible among humans, SARS
rapidly spread to Hong Kong and other provinces across China and then to
other 28 countries [6, 7]. By July 2003, it had caused 8096 confirmed cases
of infection in 29 countries, 774 (9.6 %) of which were fatal http://www.who.int/csr/sars/country/table2004_04_21/en/. The second outbreak in 2004 only caused 4 infections with no mortality nor further transmission [8].
The MERS epidemic emerged in the Kingdom of Saudi Arabia (KSA) since June
2012, with a similar clinical syndrome to SARS but seemingly less
transmissible. In addition to respiratory illness, renal failure was
identified in some severe cases [9–11]. Unlike SARS which had numerous
super-spreader events, most MERS cases were independent clusters and limited
to countries in the Middle East, particularly in KSA. Limited MERS cases
have been reported in African and European countries and the United States
of America, but exclusively in individuals travelling back from the Middle
East. Some patients were reported to have a history of contact with camels
while many other cases lacked this epidemiological link [9–11]. The MERS
pandemic in the Republic of Korea in 2015 was caused by a single person who
returned from travel in the Middle East. This made the Republic of Korea to
be home to the second largest MERS epidemic with a total of 185 confirmed
cases and 36 deaths [11, 12]. By 18 August 2015 a total of 1413 laboratory-
confirmed cases of MERS have been reported worldwide with a median age of 50
years, including 502 related deaths. The mortality of MERS (approximately
35 %) is much higher than that of SARS (around 10 %).
SARS-CoV and MERS-CoV represent two different species in the genus
Betacoronavirus
Genomic structure and taxonomic classification
SARS-CoV and MERS-CoV share similar genome organization with other
coronaviruses, but display unique genomic structures and evolutionary
lineages. The coronavirus genome possesses 6-to-7 major open reading frames
(ORFs) in the characteristic gene order in the 5’ to 3’ direction: ORF1a
and 1b which comprise two-thirds of the genome and encode the nonstructural
polyproteins, and four ORFs downstream that encode structural proteins:
spike protein (S), envelope protein (E), membrane protein (M) and
nucleocapsid protein (N). Some coronaviruses have a hemagglutinin-esterase (
HE) gene between ORF1b and S. Besides the coronavirus-conserved genes, the
SARS-CoV genome contains a number of specific accessory genes including
ORF3a, 3b, ORF6, ORF7a, 7b, ORF8a, 8b and 9b [13–15]. Comparably, MERS-CoV
encodes five unique accessory genes, designated ORF3, ORF4a, ORF4b, ORF5 and
ORF8b. None of these genes have been shown to be related to other known
coronavirus genes at the time of discovery [16, 17]. MERS-CoV was found to
have 75 and 77 % amino acid (aa) sequence identity in 7 conserved replicase
genes with two previously identified bat coronaviruses: BtCoV-HKU4 and BtCoV
-HKU5. Based on the classification criteria of the the International
Committee on Taxonomy of Viruses (ICTV), SARS-CoV and MERS-CoV represent two
novel distinct coronavirus species in the genus Betacoronavirus (Fig. 1a
and Table 1) [10, 18, 19]. Members of betacoronaviruses are separated into
four lineages, A, B, C and D. SARS-CoV and MERS-CoV are clustered in lineage
B and C, respectively [18].
Fig. 1
figure1
Phylogenetic analysis of bat coronaviruses with other coronaviruses. The
phylogenetic tree was constructed based on 816-nt partial RdRp sequences (a)
and full-length spike protein sequences (b). Available sequences were
retrieved from GenBank and aligned using ClustalW. The alignment was used to
construct tree by MEGA (Version 5.1) with the neighbor-joining statistical
method. Bootstrap values were calculated from 1000 replicates (values ≥50
are shown). Bat coronaviruses are drawn in bold and named following bat
species, plus BtCoV, strain name, and GenBank accession number
Full size image
Table 1 Comparison of bat coronaviruses with SARS-CoV or MERS-CoV in
conserved replicase domains and structural proteins
Full size table
Receptor usage
The S protein of coronaviruses is a surface-located trimeric glycoprotein
consisting of two subunits: the N-terminal S1 subunit and the C-terminal S2
subunit. The S1 subunit specializes in recognizing and binding to the host
cell receptor while the S2 region is responsible for membrane fusion.
Compared with the S2, the S1 subunit shows much higher variability [20].
Owing to its function of receptor binding, the variation in S protein
defines in large part the tissue tropism and host range of different
coronaviruses [21].
Angiotensin-converting enzyme 2 (ACE2) was identified to be the functional
receptor of SARS-CoV [22–24]. A 193 aa fragment (aa 318–510) of SARS-CoV S
protein was demonstrated to bind ACE2 more efficiently than the full S1
domain and was defined as the receptor-binding domain (RBD) of SARS-CoV [25]
. A loop subdomain (aa 424–494) that directly contacts with ACE2 was
further identified as the receptor-binding motif (RBM) by crystal structure
analysis [26]. In the RBM, several aa residues were found to be critical for
receptor binding and changes in these key residues resulted in different
binding efficiency among different SARS-CoV isolates [26–28].
Dipeptidyl peptidase 4 (DPP4, also known as CD26) was identified as a
functional receptor for MERS-CoV [29] and it is relatively conserved among
mammalian species. Published results indicated that MERS-CoV can infect and
replicate in most cell lines derived from human, non-human primate, bat,
swine, goat, horse, rabbit, civet, and camel, but not from mice, hamster,
dog, ferret, and cat [29–36]. DPP4 from camel, goat, cow, and sheep can be
also recognized by MERS-CoV and can support MERS-CoV replication [30, 35].
Resolved crystal structures demonstrate that DPP4-recognizing RBD is
localized to the S1 C-terminal portion of S protein of MERS-CoV [37–39].
The RBD of MERS-CoV consists of ~240 residues, spanning aa 367–606, which
fold into a structure consisting of two subdomains, the core subdomain and
the external subdomain. The core subdomain of MERS-CoV RBD is structurally
similar to that of the SARS-CoV RBD, but the external subdomain (also named
as RBM) is different to that of the SARS-CoV [37–39].
Bat origin of SARS-CoV
Civets are intermediate and trasnmission host of SARS-CoV
Epidemiological survey showed that early cases of SARS in 2002–2003 and all
4 cases in 2003–2004 had a history of animal contact through animal trade
in wet markets or in restaurants where live animals were kept in Guangdong
Province. Molecular detection and virus isolation studies suggested that the
pandemic-causing SARS-CoV originated from traded civets in wet markets.
This was indirectly confirmed by the massive culling of market civets, which
was believed to play a major role in efficiently containing the SARS
pandemics and no further SARS case was reported after 2004 [40–42].
However, subsequent extensive epidemiology studies did not find SARS-CoV in
farmed or wild-caught civets, indicating that other animal(s) was involved
in SARS-CoV transmission in the animal market or other trading activities
and civets are unlikely the natural reservoir of SARS-CoV [43–45].
Discovery of diverse SARS-like coronaviruses in bats
Several years before the outbreak of SARS, two other zoonotic viruses, Nipah
virus and Hendra virus, emerged in Asia and Australia and they were both
known to be originated from bats [46, 47]. These led scientists to consider
bats in the search of reservoirs of SARS-CoV. In 2005, a breakthrough was
made as two independent research groups reported, almost simultaneously, the
discovery of novel coronaviruses related to SARS-CoV in horseshoe bats (in
the genus Rhinolophus) in China, which were termed SARS-like coronavirus (SL
-CoV) [48, 49]. These bat SL-CoVs from both mainland China and Hong Kong
manifested genome sequence identity of 88–90 % among themselves and 87–92
% identity to human or civet SARS-CoV isolates. The unique set of ORFs
exclusively found in SARS-CoV was also present in bat SL-CoVs, demonstrating
the close phylogenetic relationship between SARS-CoV and SL-CoV. The
discovery of bat SL-CoV boosted researchers’ interest in coronavirus
surveillance studies in bats. In following years, SL-CoV RNA was detected in
Rhinolophus species of a wider geographic range in China. The provinces or
regions where SL-CoV-positive bats were captured included Hong Kong, Guangxi
, Hubei, Shandong, Guizhou, Shaanxi and Yunnan [50–53]. 7 conserved
replicase domains in orf1ab of these SL-CoVs found in China were compared
with those of SARS-CoV (Table 1). They all shared higher than 95 % aa
sequence identity with SARS-CoV in the concatenated domains and therefore
can be considered to belong to SARS-CoV species [54].
SL-CoVs were also discovered in rhinolophids from Slovenia, Bulgaria and
Italy in Europe [55–57]. These European SL-CoVs exhibited significant
genetic variation from Chinese isolates. The strain BM48-31 from Rhinolophus
blasii in Bulgaria was highly divergent from Chinese isolates, displaying
major sequence differences in several genes including ORF3b and ORF6 and
lacking the coding region of ORF8 in its genome [55]. In Africa, novel
betacoronaviruses related to SARS-CoV have been detected in Hipposideros and
Chaerophon species from Ghana, Kenya and Nigeria. However, compared with
Asian and European SL-CoVs, these viruses of non-rhinolophid origin were
phylogenetically distant to SARS-CoV. The Western African isolates even
formed a potential new lineage of Betacoronavirus in the phylogenetic tree (
Fig. 1a) [58–60].
Most related ancestor of SARS-CoV in bats
Although the aforementioned bat SL-CoVs showed high sequence identity to
SARS-CoV, two deletions were present in the RBM of their S proteins [48, 49]
. The differences in RBM substantially changed the receptor usage. In a
study using an HIV-based pseudovirus system and cell lines expressing human,
civet, and horseshoe bat ACE2 molecules, the bat SL-CoV Rp3 S protein
demonstrated its inability to use ACE2 as cell receptor [61]. However, the
chimeric Rp3 S protein carrying the RBD of SARS-CoV S protein was conferred
the capability of cell entry via human ACE2 [61]. These results suggested
that bat SL-CoVs such as Rp3 were unlikely to cause human infection.
Therefore, they may not be considered as the direct progenitor of SARS-CoV.
Besides, the theory of bat origin of SARS-CoV lacked a powerful support due
to the failure of direct isolation of SL-CoV from bats, despite numerous
trials by our group as well as many others around the world.
During our longitudinal surveillance at a Rhinolophus sinicus colony in
Yunnan Province over the years, a major breakthrough came in 2013 when
diverse SL-CoVs were discovered in the single colony [53]. In this colony,
there were at least 7 different strains related to SARS-CoV, HKU3, Rs672 or
Rf1, based on analysis of the region corresponding to SARS-CoV RBD.
Intriguingly, unlike all previously described SL-CoVs, two strains,
designated Rs3367 and RsSHC014, did not contain the deletions in this region
. Rs3367 showed a particularly high sequence identity to SARS-CoV in RBD and
was identical to SARS-CoV in several key amino acid residues known to be
important for receptor binding [53]. Whole genome sequencing revealed that
Rs3367 and RsSHC014 shared more than 95 % genome sequence identity with
human and civet SARS-CoV, which was remarkably higher than that of any other
bat SL-CoV (76 to 92 %). Regarding individual genes, the amino acid
sequence identity between Rs3367 or RsSHC014 and SARS-CoV was higher than 96
% in ORF1a, 1b, 3a, 3b, E, M and N genes [53]. Most importantly, a live SL-
CoV was isolated for the first time from bat fecal samples [53]. This virus,
termed WIV1, had almost identical sequence (99.9 %) to Rs3367 and was
demonstrated to use ACE2 molecules from humans, civets and Chinese horseshoe
bats for cell entry. It also displayed infectivity in cell lines from a
broad range of species including human, pig, and bat. Furthermore, the close
relatedness between WIV1 and SARS-CoV was confirmed by neutralization
effect of convalescent SARS patient sera on WIV1 [53]. The isolation of a
bat SL-CoV genetically closely resembling SARS-CoV and having a functional S
protein capable of using the same ACE2 receptor as SARS-CoV provided robust
and conclusive evidence for the bat origin of SARS-CoV.
Possible origin of SARS-CoV from recombination of different SL-CoVs
Despite the fact that Rs3367 or WIV1 is unprecedently close to SARS-CoV in
terms of RBD region and genome identity, still there are gaps between them
and the immediate ancestor of SARS-CoV. ORF8 is a highly variable gene and
remarkable differences can be observed among SARS-CoVs and SL-CoVs of
different host origins. Isolates from civets and from early phase of the
2002/2003 pandemic contained a single long ORF8, while in the human SARS-CoV
isolates from the middle and late phase of the pandemic the ORF8 was
disrupted into two ORFs, ORF8a and ORF8b, as a result of the acquisition of
a 29-nt deletion after interspecies transmission to humans [8, 40, 62]. The
SL-CoVs from Rhinolophus sinicus, including Rs3367, however, had a single
ORF8 with only 32–33 % amino acid identities to that of civet SARS-CoV. In
contrast, the ORF8 of two novel SL-CoV strains recently reported in Yunnan
from another rhinolophid species, Rhinolophus ferrumequinum, exhibited
exceptionally high (81.3 %) amino acid identity to civet SARS-CoV SZ3 [63].
This is consistent with isolate Rf1, a SL-CoV reported earlier from R.
ferrumequinum in Hubei Province, of which the ORF8 shared 80.4 % amino acid
identity to SZ3 [48]. Potential recombination sites were identified around
the ORF8 region between SL-CoVs from R.sinicus and R.ferrumequinum and it
has been suggested that the ancestor of civet SARS-CoV probably acquired
ORF8 from R.ferrumequinum SL-CoVs by recombination [63].
Animal origins of MERS-CoV
As with SARS-CoV, most early MERS cases had contact history with animals, e.
g., dromedary camels [64, 65]. MERS-CoV RNA was detected in camels from
Saudi Arabia, Qatar and Egypt and showed high similarities (>99 %) to human
MERS-CoV in genomic sequences [66–71]. Serological evidence further
confirmed a high prevalence of MERS-CoV infections in camels in the Middle
East [72–77], Africa [78–80] and Europe (Spain) [73]. The neutralization
antibodies in camels could be traced back to 1983 [73, 80]. These results
strongly suggested that MERS-CoV infection in humans were transmitted
through close contact with infected camels [66, 76, 81–83].
Bat viruses related to MERS-CoV
Prior to the emergence of MERS-CoV, a group of bat coronaviruses had been
reported including Tylonycteris bat coronavirus HKU4 (BtCoV-HKU4) in
Tylonycteris bats and Pipistrellus bat coronavirus HKU5 (BtCoV-HKU5) in
Pipistrellus bats in China [50, 84, 85], E.isa/M/Spain/2007 in Eptesicus
isabellinus bats in Spain [86] and N.noc/VM366/2008/NLD in Pipistrellus
pipistrellus bats in the Netherlands [87]. Based on genomic sequence
analysis, these bat coronaviruses were grouped into lineage C of the genus
Betacoronavirus. After the outbreak of MERS, MERS-CoV related coronaviruses
were found in more bat species and countries [88–96]. Among these viruses,
full-length or near full-length genomes of BtCoV-HKU4, BtCoV-HKU5, SC2013
and NeoCoV have been characterized. By genomic analysis of lineage C
betacoronaviruses, MERS-CoV derived from camels show high similarities to
human MERS-CoV with >99.5 % nt identities, confirming that the human and
camel isolates belong to the same coronavirus species. Bat HKU4, HKU5,
NeoCoV and SC2013, shared 69.8, 70, 85.6 and 75.6 % nt identities with MERS-
CoV at genomic level, respectively. Seven conserved replicase domains in
orf1ab of MERS-CoV related viruses were compared with MERS-CoV (Table 1).
The concatenated translated domains of NeoCoV shared 95 % aa sequence
identity with MERS-CoV and it could be classified as the same MERS-CoV
species [54]. Other bat coronaviruses, HKU4, HKU5 and SC2013, could be
considered as different coronavirus species. The most recent ancestor
analysis speculated that MERS-CoV may have jumped from bats to camels
approximately 20 years ago in Africa, with camels then being imported into
the Arabian Peninsula [92], while HKU5 and MERS-CoV may have diverged from
their common ancestor about 400 to 500 years ago [85].
Although NeoCoV is closer to MERS-CoV than other bat coronaviruses at
genomic level, the phylogenetic analysis of the spike protein showed that
HKU4 is the most closely related to MERS-CoV among all currently known bat
coronaviruses, sharing 67 % sequence identity (Fig. 1b). This is correlated
with the capability of HKU4 of using DPP4 as its functional receptor.
However, HKU4 preferred bat DPP4 over human DPP4, whereas MERS-CoV showed
the opposite trend [97]. It was suggested that MERS-CoV ancestors had been
circulating in bats for very long time. MERS-CoV has evolved to adapt to use
human receptor and the DPP4-recognizing bat coronaviruses like HKU4 may
follow up, thereby posing a serious risk to human health [97, 98].
Comparison of transmission of MERS-CoV and SARS-CoV
Both SARS-CoV and MERS-CoV are emerging zoonotic pathogens that crossed the
species barriers to infect humans [10, 53, 99]. Evidence showed that SARS-
CoV and MERS-CoV originated from bats, the nature reservoirs, then
transmitted to human via intermediate hosts civets and camels, respectively
[10, 40, 53, 81, 100]. Human SARS-CoV infection originated from the direct
contact between humans and civets in markets or restaurants. Closing wet
markets and cleaning civet cut off the spread chain of SARS-CoV and
effectively ended the SARS epidemic [40, 42, 101]. In contrast, MERS-CoV is
believed to have existed in camels for a very long time and camels are
widely distributed in Middle East and African countries, serving as
important transport vectors and sources of meat and milk for the local
population. Therefore, it is difficult to adopt the same strategy of SARS-
CoV control in the prevention of future MERS-CoV outbreaks. Until a
comprehensive approach is found, which most likely will involve the
effective vaccination of camels against MERS-CoV among other measures, it is
envisaged that sporadic human infection will persist for some time in the
future [11, 70].
Bat coronaviruses and human coronavirus 229E (HCoV-229E) and NL63 (HCoV-NL63)
HCoV-229E was found in the 1960s and causes comparatively mild common colds
worldwide [102]. A bat coronavirus detected in Hipposideros caffer ruber in
Ghana termed Hipposideros/GhanaKwam/19/2008 was genetically related to HCoV-
229E. Its RdRp fragment shared 92 % nucleotide sequence identity with HCoV-
229E and they were predicted to share a most recent common ancestor (MRCA)
only 200 years ago [58]. A recent study characterized more 229E-related
coronaviruses discovered in hipposiderid bats from Ghana on full genome
level. These bat coronaviruses were more diversified and formed a single
viral species with HCoV-229E. Interestingly, phylogenetic analysis revealed
the intermediate position of a 229E-related alpaca virus between bat and
human viruses. These findings suggested the ancestral origin of HCoV-229E in
hipposiderid bats and the role of camelids as potential intermediate hosts
was hypothesized [103].
HCoV-NL63 was first isolated from babies suffering of pneumonia and
bronchiolitis in 2004 [104]. To date, HCoV-NL63 has been found worldwide
with up to 9.3 % detection rate in hospitalized respiratory tract samples [
105]. In 2010, a bat coronavirus termed ARCoV.2 (Appalachian Ridge CoV)
detected in North American tricolored bat (Perimyotis subflavus) in the US
showed close relationship with HCoV-NL63. The MRCA for HCoV-NL63 and ARCoV.2
was predicted to have existed 563 to 822 years ago [106, 107]. Further
analysis indicated that HCoV-NL63 can replicate in cell lines derived from
the lungs of tricolored bats [107]. These results suggest that prototypes of
HCoV-NL63 may also exist in bats and there may also be a bat origin of this
human coronavirus.
Conclusions
Although the study of bat-borne coronaviruses has only started just about 10
years ago, the scientific community has already learnt a great deal of
useful lessons which will be instrumental in mitigating, predicting, and
preventing future zoonotic coronavirus outbreaks. Some of these lessons are
summarized below.
Bats harbor coronaviruses with great genetic diversity. It is believed that
most, if not all, currently circulating alphacoronaviruses and
betacoronaviruses in different mammals are evolutionally linked to ancestral
coronaviruses originated from bats. Different species of rhinolophid bats
in China carry genetically diverse SARS-like coronaviruses, some of which
are direct ancestors of SARS-CoV and hence have the potential to cause
direct interspecies transmission to humans. Meanwhile, different coronavirus
species closely related to MERS-CoV are circulating in bats. Bats are
likely natural reservoirs of MERS-CoV or an ancestral MERS-like CoV. It is
hypothesized that bat MERS-like CoV jumped to camels or some other as yet
unidentified animal several decades ago. The virus evolved and adapted with
accumulating mutations in camels and then was transmitted to humans very
recently. It took almost a decade from the first discovery of SL-CoV in bats
to the final isolation of the SARS-CoV ancestral virus from bats, so
continuing surveillance is vital to uncover the origin of MERS-CoV and bats
should certainly be a priority of research. Besides, as the spike protein
and host receptor are key factors of cross-species transmission of
coronaviruses, characterization of the receptor and key binding sites of the
spike protein will be important in estimating host tropism of bat
coronaviruses and predicting spillover risk.
With human activity increasingly overlapping the habitats of bats, diseases
outbreaks resulted from spillover of bat coronaviruses will continue to
occur in the future despite the fact that direct transmission of bat
coronaviruses to humans appears to be rare. To better prepare ourselves in
predicting and preventing the next emergence of a coronavirus disease, it is
necessary to maintain our vigilance in long-term coronavirus surveillance
studies in bats as well as in other wildlife and livestock. Combined with
other laboratory-based studies such as receptor specificity, pathogenesis
and animal infection, a focus on continued surveillance will help us to
improve risk assessment as well as to reveal the potential intermediate
hosts that may play an important role in the interspecies transmission of
various known and as yet unknown bat coronaviruses.
http://virologyj.biomedcentral.com/articles/10.1186/s12985-015-0422-1 | k**********4
发帖数: 16092 | 5 另外，我看你没有科学家的冷静和客观态度，多次用侮辱性的词汇，如果山甲论真那么
不堪的话，不会有那么多科学家赞同，nature也不会转发这个消息，至少有可能是对的
【在 k**********4 的大作中提到】
: 我看你一直认为搞基因组研究要拿到材料，一直强调Wong没摸过山甲，其实不是这样的
: ，从已经发表的基因序列就可以比较，不一定自己要从测一遍
:
: preprint
| w*****i
发帖数: 1 | 6 它不是抓完了蝙蝠，抓穿山甲，现在又在抓老鼠么？
lol
竟然还有人看它叨逼叨的狗屁论文？？
preprint
【在 C*I 的大作中提到】
: lubbock34，又名“胡汉三又回来了”，从名字判断，其年龄在53岁以上，职业应当是
: 个5毛。因为其马甲连续系列被多少穿戴使用，难说不是个5毛团伙。
: 最近这些天，lubbock一直拼命宣传病毒不是武汉所泄露出来的，明说暗示可能是美国
: 人投的毒。因此，刻意从bioRxiv上找来了一个matthew wong的未经正式发表preprint
: 的paper来佐证。说蝙蝠病毒不是新冠状病毒的initial病毒，穿山甲所带的冠状病毒才
: 是这次武汉病毒的原始宿主。为此，接二连三的在买买提开贴，带领一帮大小男女五毛
: ，乎着号子制造舆论风潮，误导视听，百般为病毒所解脱。
: 既然lubbock过来过去都是这个什么马来西亚人matthew wong的论文，那我们就看看这
: matthew wong到底是个什么人物了。
: 按照bioRxiv的公开介绍，这watthew wong，只是一个大学本科/bs的学生，既没有硕士
| p********2
发帖数: 1 | | W******y
发帖数: 1 | 8 智障就是智障
原始病毒来自蝙蝠，就好比sars的原始病毒也是来自蝙蝠一样
但是蝙蝠身上的病毒很难直接感染人类
而是先感染和人类密切相关的另一种动物，例如sars的果子狸，MERS的骆驼
人们把果子狸和骆驼就叫做“中间宿主”
武汉肺炎，也是来自蝙蝠，但是造成人感染的，现在怀疑是那个叫做穿山甲的“中间宿
主”，或者其它动物，找到这个中间宿主很重要。知道传播途径才好杜绝
懂了没？一点都不懂，智障一样理直气壮，替你父母丢人现眼么？
【在 w*****i 的大作中提到】
: 它不是抓完了蝙蝠，抓穿山甲，现在又在抓老鼠么？
: lol
: 竟然还有人看它叨逼叨的狗屁论文？？
:
: preprint
| C*I
发帖数: 4736 | 9 先别说别人智障。 你应当先去看看石正丽2013年11月份发在nature上的研究报告。 在
那个报告里，石正丽经过大量的抓蝙蝠和其它动物比方果子狸到武汉病毒所研究后发现。
1. 果子狸并不是当年的sars病毒的原始宿主。而原始宿主是来自云南山洞里的菊头福
蝙蝠。其与当年sars病毒的相似度高达98%上下。
2. 蝙蝠传染sars给人，并不需要其它宿主，而是直接可以传染给人（当然了，我不知
道他们怎么弄明白这个问题的）。她们的研究报告白纸黑字，斑斑可考，无法撼动。
【在 W******y 的大作中提到】
: 智障就是智障
: 原始病毒来自蝙蝠，就好比sars的原始病毒也是来自蝙蝠一样
: 但是蝙蝠身上的病毒很难直接感染人类
: 而是先感染和人类密切相关的另一种动物，例如sars的果子狸，MERS的骆驼
: 人们把果子狸和骆驼就叫做“中间宿主”
: 武汉肺炎，也是来自蝙蝠，但是造成人感染的，现在怀疑是那个叫做穿山甲的“中间宿
: 主”，或者其它动物，找到这个中间宿主很重要。知道传播途径才好杜绝
: 懂了没？一点都不懂，智障一样理直气壮，替你父母丢人现眼么？
| C*I
发帖数: 4736 | 10 我读了，大体说了三点：
1. This is strong evidence that SARS-CoV-2 is not the product of genetic
engineering.
Although genomic evidence does not support the idea that SARS-CoV-2 is a
laboratory construct, it is currently impossible to prove or disprove the
other theories of its origin described here, and it is unclear whether
future data will help resolve this issue.
足够坚实的证据显示，新冠状病毒 Sars-CoV-2 不是人工制造的产品。不过，虽然基因
证据不支持Sars-Cov-2 不是实验室的产物，但现在还没有办法从理论上证实和否定它
的绝对来源，这需要其它更多的证据和资料来帮助解决这个问题。
2. Although the bat virus RaTG13 remains the closest relative to SARS-CoV-2
across the whole genome, the Malayan pangolin CoV is identical to SARS-CoV-2
at all six key RBD residues (Figure 1). However, no pangolin CoV has yet
been identified that is sufficiently similar to SARS-CoV-2 across its entire
genome to support direct human infection. In addition, the pangolin CoV
does not carry a polybasic cleavage site insertion.
从整体基因看，蝙蝠病毒RaTG13与Sars-Gov-2 最接近。 马来西亚的穿山甲病毒Cov 相
对于Sars-CoV-2 只有6个RBD接近。 但是，没有证据证明穿山甲病毒从整体基因上与
Sars-CoV-2 有相关性可以感染人。 另外， 穿山甲病毒Cov也不支持具备多基点插入的
特治。
3.同时，这份研究报告强调，不排除有其它动物充当了把病毒从蝙蝠到人的传染的中间
媒介。但现在无法证实。
【在 p********2 的大作中提到】
: 有没有人评论一下这个paper?
: http://virological.org/t/the-proximal-origin-of-sars-cov-2/398
| | | C*I
发帖数: 4736 | 11 那傻逼很搞笑的捏造了一个马来西亚的本科学生，通过google发现了6个所谓的氨
基酸PRRA。 用无耻，扯蛋，捏造的故事为病毒所洗地。彰显了一个五毛的无知与无畏。 | l*******4
发帖数: 1 | 12 还有RBD序列也不一样
关键是这篇文章通讯作者是他老板
其他coauthor 也都是phd
畏。
【在 C*I 的大作中提到】
: 那傻逼很搞笑的捏造了一个马来西亚的本科学生，通过google发现了6个所谓的氨
: 基酸PRRA。 用无耻，扯蛋，捏造的故事为病毒所洗地。彰显了一个五毛的无知与无畏。
| C*I
发帖数: 4736 | 13 你除了捏造，懂个屁！
【在 l*******4 的大作中提到】
: 还有RBD序列也不一样
: 关键是这篇文章通讯作者是他老板
: 其他coauthor 也都是phd
:
: 畏。
| C*I
发帖数: 4736 | 14 现在Lubbock和没有逼装逼的马甲maynew 在那里一唱一合用马来西亚本科学生google来
的东西所写的没有公开发表和被review的所谓paper在这里为病毒所洗地。还在这里给
那个马来西亚本科生捏造了“6个氨基酸新发现”。 干劲很大，勇气十足，牛逼冲天，
厉害得不得了！
我日， 五毛这东西真他妈的厉害。 | z****X
发帖数: 1 | 15 他连我帖子都不敢接
五毛还没得肺炎吗
你所造出来这个可是会感染蛋蛋的， 活下来也是断子绝孙哦 | l*******4
发帖数: 1 | 16 还有发国科学家也发现了
【在 C*I 的大作中提到】
: 现在Lubbock和没有逼装逼的马甲maynew 在那里一唱一合用马来西亚本科学生google来
: 的东西所写的没有公开发表和被review的所谓paper在这里为病毒所洗地。还在这里给
: 那个马来西亚本科生捏造了“6个氨基酸新发现”。 干劲很大，勇气十足，牛逼冲天，
: 厉害得不得了！
: 我日， 五毛这东西真他妈的厉害。
| l*******4
发帖数: 1 | 17 我没有捏造
【在 C*I 的大作中提到】
: 你除了捏造，懂个屁！
| C*I
发帖数: 4736 | 18 法国个屁，你都可以给本科学生捏出发现了“6个氨基酸”，请问你什么捏不出来？ 你
最大的特点就是说谎，造谣！ 你前几天还说马来西亚人是什么牛逼科学家呢。
【在 l*******4 的大作中提到】
: 还有发国科学家也发现了
| l*******4
发帖数: 1 | 19 我说的是4个氨基酸，你怎么给多加出来两个呢？
【在 C*I 的大作中提到】
: 法国个屁，你都可以给本科学生捏出发现了“6个氨基酸”，请问你什么捏不出来？ 你
: 最大的特点就是说谎，造谣！ 你前几天还说马来西亚人是什么牛逼科学家呢。
| z****X
发帖数: 1 | 20 穿山甲的那个也是无毒所和华南农业 弄的宏基因库，洗不白的
五毛里面没有千老坐镇，洗都不会洗
你就告诉我你家病毒库里的东西都是怎么到武汉的就可以了
文章里各种全国五省采集样本 | | | z****X
发帖数: 1 | 21 是不是人造的姑且不谈
大自然病毒搬运工你跑不了的 | l*******4
发帖数: 1 | 22 穿山甲那个不是五毒所和华南农大上传的数据到宏基因库
【在 z****X 的大作中提到】
: 穿山甲的那个也是无毒所和华南农业 弄的宏基因库，洗不白的
: 五毛里面没有千老坐镇，洗都不会洗
: 你就告诉我你家病毒库里的东西都是怎么到武汉的就可以了
: 文章里各种全国五省采集样本
| z****X
发帖数: 1 | 23
不是个屁 弄了4年 全国共享 自己去看沈永义采访 新华网爆的
你昨天不是说穿山甲是走私的吗，来来来
【在 l*******4 的大作中提到】
: 穿山甲那个不是五毒所和华南农大上传的数据到宏基因库
| l*******4
发帖数: 1 | 24 这一下就透漏了你是行外人了
【在 z****X 的大作中提到】
:
: 不是个屁 弄了4年 全国共享 自己去看沈永义采访 新华网爆的
: 你昨天不是说穿山甲是走私的吗，来来来
| z****X
发帖数: 1 | 25 你先去读读人家去年9月发的原始文章再说吧
别老贴网上的二手货 | z****X
发帖数: 1 | 26 需不需要我再给你透露下宏基因库的合作单位以及分配方式？
上面没告诉你这个库的资源是怎么分的吗 |
|
