閻麗夢博士所撰寫的武漢肺炎科學文章,一時間便引起了極大的迴響。949Please respect copyright.PENANAkgzqpHF1Tg
本篇文章將嘗試盡量精簡文章各論據,方便大家理解以及分析。949Please respect copyright.PENANAyZX2YhD4Ew
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文章將會大致分成兩部份,上半部將會直述閻博士的文章內容,下半部份將會是我對文章的個人理解及分析,歡迎各位巴絲詳細閱覽後一齊留言討論。949Please respect copyright.PENANAK8ZHQTlwcd
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SARS-CoV2,源自武漢,因而被冠上武漢肺炎稱號。949Please respect copyright.PENANAqQQMvjF6Gs
(圖1)下列將依照基因排組的相似度,列出現時已知的蝙蝠冠狀病毒(穿山甲身上找到的冠狀病毒將不會計算在內)。949Please respect copyright.PENANAPcG0lZEjmm
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1.RaTG13,2013年潼關縣山洞蝙蝠糞便中找到的冠狀病毒,TG解作為潼關的英文(TongGuan)。949Please respect copyright.PENANAAdFRYr6Mbl
它與武肺的基因排組相似度為96.2%,由石正麗教授團隊找出。949Please respect copyright.PENANAeDNCOpwjJ4
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(在武肺發生後,石教授搜索實驗室各種蝙蝠標本,在裡頭找出RaTG13的存在,因而把完整排組公開;949Please respect copyright.PENANAfDDYLqoB2f
RaTG13的部份排組,曾在2015-2016年期間出現在石教授的文獻。)949Please respect copyright.PENANALH9ZMc3bfq
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2.RmYN02,2019年雲南蝙蝠冠狀病毒,與武肺的相似度為93.3%,由石正麗教授團隊找出。949Please respect copyright.PENANAFW0WVcgffI
(在武肺發生後,石教授團隊在2020年6月底發表文章指出其存在。)949Please respect copyright.PENANAkgUTVTOmQs
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3.ZXC21/ZC45,2018年浙江省舟山市蝙蝠冠狀病毒,與武肺的相似度為89%,由重慶市中國人民解放軍第三軍醫大學軍事實驗室及南京軍區南京總醫院研究所共同合作把病毒分離出來。949Please respect copyright.PENANA1JUZ07ATJF
(早於武肺發生前,2015年7月-2017年2月期間找出,2018年在學術文章正式出現。)949Please respect copyright.PENANA9UjJTy6XTE
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基於RaTG13與武肺的吻合度暫時為最高,現今主流文章一直都引用RaTG13的數據作出分析。949Please respect copyright.PENANAd2h1wTq8el
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而閻麗夢博士在文章指出,有不少高學術水平質素的文章均對RaTG13抱有疑問,對RaTG13是否真實存在作出質疑。949Please respect copyright.PENANAEZog8nJxjx
基於這點,閻博士引用各種文獻,對RaTG13及各種在武肺發生後所找出的冠狀病毒作出質疑(她強調日後會再出一份文章綜合RaTG13的存疑之處),並提倡ZXC21/ZC45是實驗室人工方式製作武肺的「原材料」。949Please respect copyright.PENANAkU73BsfYUa
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(圖2)為方便帶出閻博士的理論,我從另一文獻(Ref1) 找出此圖,方便論述她的見解。949Please respect copyright.PENANAAPfGz7qEw3949Please respect copyright.PENANA2U3dANlfXD
她指出在氨基酸(外行人可視之為蛋白質)的排組中,ZXC21/ZC45與武肺有著一定的相似度。949Please respect copyright.PENANAJdfrOZ6ITK
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例如負責包圍病毒基因的Nucleocaspid (N)蛋白質,(圖中紅框),它與武肺有著94%的相似度。949Please respect copyright.PENANAq2d4M3Gz2J
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病毒外圍的Membrane(M)蛋白質,(圖中藍框),則有著98.6%的相似度。949Please respect copyright.PENANAwKRGVAXnG0
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綠框有著潛在影響宿主免疫功能的Orf8(8),94.2%相似度,以及紫框的Envelope(M)高達百分之百的相似度。949Please respect copyright.PENANA3Uoex1xqsg
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基於各種高相似度之處,她提出了ZXC21/ZC45很有可能是用來製作武肺的重要骨幹,意思即是將ZXC21/ZC45略加改造便能轉化成為武肺。949Please respect copyright.PENANA1FLg2yIBAj
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其後,她亦指出武肺與03年SARS有著相近的地方,故此有理由相信ZXC21/ZC45再加上03年SARS某部份的組件並加以改造後,便能夠成為今時今日的武肺。949Please respect copyright.PENANAmWPwpbJ9Tq
(此理據為文中Fig4的重點,但她圖中的數據與內容並不符合,需要讀者以人手的方式推移18位置才能理解及消化,故此我無意轉載在這裡,有心人可自行閱讀。)949Please respect copyright.PENANAq1ivAZgFyM
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(圖3)為了加強自己論點的說服力,她對武肺和ZC45的Spike Protein基因排組作出對比(Spike Protein為武肺病毒與人體細胞表面接觸的重要手段)。949Please respect copyright.PENANAaofl756J50949Please respect copyright.PENANAkSnvMvUDnE
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她發現,武肺裡頭存在 Restriction Enzyme EcoRI及BstEII的排組。949Please respect copyright.PENANAaK1AlppI19
Restriction Enzyme是蛋白質的一種,它的特性是對特定的基因排組進行切割。949Please respect copyright.PENANAZQtx5NO8GK
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以EcoRI為例,當它發現 gaa tcc的排序後,它便會將排組斬開兩截。而BstEII見到 ggt tacc排組後,同樣亦會進行切割。949Please respect copyright.PENANAUn1YuCgxnJ
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換句話說,如果我們在武肺那段排組中添進EcoRI及BstEII的話,劃下紅線的那段基因排組便會被切割出來。949Please respect copyright.PENANASY5mTCbecS
被切割出來的空位,順其然便能補上另一段排組,再透過蛋白質Ligase將那新一段的排組無縫地聯合在空隙裡頭。949Please respect copyright.PENANAvk50Mi6dsi
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無獨有偶,在ZC45的排組中,她發現了類近能夠被EcoRI及BstEII偵測出來的排序。949Please respect copyright.PENANAtcLSFfSvmU
雖然排組上有著細微不同的地方,949Please respect copyright.PENANAUE85BJP1B8
(EcoRI: 武肺:gaa ttc,ZC45:gaa cac)949Please respect copyright.PENANAVSBDH1hyy1
(BstEII:武肺:ggttacc,ZC45:gaatacc)949Please respect copyright.PENANAF1x5fMx56L
但她認為只要稍為略下功夫的話便能將ZC45的排組轉換成為相應被Restriction Enzyme辨認的排組,方便將ZC45個別排組轉移到武肺排組之用。949Please respect copyright.PENANAqHBpdqobK8
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(圖4)她其後亦翻查石正麗教授的文章,發現她兩道文獻裡頭,病毒排組中均出現了以EcoRI為首的武肺排組,因而更有理由相信石教授利用了Restriction enzyme或類近原理的方式把個別基因段落互相在病毒中轉移。949Please respect copyright.PENANAMU0WUtoCan949Please respect copyright.PENANAaQSNMC39bH
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(圖5)武肺的其中一個獨特之處,就是擁有一段沒能夠在同類別的冠狀病毒中(包括03年SARS)找到的polybasic cleavage site排組(圖中綠色英文字母),這段排組賦予了武肺另一種入侵細胞的手段,因而能夠避開Chloroquine的阻截。949Please respect copyright.PENANAV3OgabbJFB949Please respect copyright.PENANApbptUbMBC7
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這排組並非獨一無二,事實上亦能在其他類別中的病毒找到,而閻博士亦特別指出,石教授在2017年一篇論文中的病毒亦有出現類近的基因排組。949Please respect copyright.PENANAIhO1SEqBMJ
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(圖6)在這段polybasic cleavage site排組(PRRA)中,閻博士發現了一道異常之處。949Please respect copyright.PENANA01q1gbIGys949Please respect copyright.PENANA5xs9X1c1Fp
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PRRA是蛋白質的代號,而PRRA上面的英文字母則是所對應的基因英文字母排組。949Please respect copyright.PENANAqkm2YbXocK
現今的理論是,每三個基因英文字母便能「轉變」成為一個蛋白質,而製造R蛋白質的英文字母組合包括有 cgt , cgc , cga 以及cgg。949Please respect copyright.PENANAEbarIkaEM5
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對此,閻博士引用學術文章,表示武肺甚少會利用cgg「轉變」成為R蛋白質,大多數的情況下均會用上cgt。949Please respect copyright.PENANAXR13VLtw5S
而且同時出現cggcgg的重覆排組更是極為「罕有」,有著人工製造的嫌疑。949Please respect copyright.PENANAvTWezWr3Xk
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再加上gcggg是另一隻Restriction Enzyme FauI的辨認排組,閻博士推斷這大有可能是以人工方式加插這段polybasic cleavage site的證據。949Please respect copyright.PENANAp8juzUKSHe
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總結而言,閻博士基於下列五點,得出武肺大有可能是人工製造的病毒。949Please respect copyright.PENANAEG1s5fYmnI
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1.ZC45/ZC21與武肺排組有著相對高的相似度。949Please respect copyright.PENANAv93YFbN6dm
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2.武肺與03年SARS的S protein有著一定的相似度。949Please respect copyright.PENANAqLli3MZ3kC
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3.武肺的S protein排組有著EcoRI及BstEII的排組,而ZC45亦有非常類近的排組。949Please respect copyright.PENANA5PT0TAfQTD
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4.武肺Polybasic Cleavage Site有著極為罕有的基因排組及對應的Restriction Enzyme。949Please respect copyright.PENANAHau9YCJYCe
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5.大自然間從ZC45跳到武肺的排組近乎是沒有可能/需要極長時間才能發生的事情。949Please respect copyright.PENANAREbD6sQ1Tn
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以下純為我個人的見解及分析。949Please respect copyright.PENANA0jmqbfmCgw
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要徹底反對或指出一方證據的不是,某程度上要用上相應更多的證據才能把對方的理論推番。949Please respect copyright.PENANADGbf1AubJU
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閻博士的思路是單純引用別人的學術文章,再加以幾句修飾便完全漠視了RaTG13及與武肺第二相近的RmYN02存在,這點明顯是有所偏頗,有待她日後所補充的文章才有機會可以確立她的這個論述。949Please respect copyright.PENANAy3eUYvPjfF949Please respect copyright.PENANAVmoALdpvse
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(圖7)另外,她在文中引用了石教授08年的一份文章,暗指她曾利用EcoRI及BstEII的手法轉換基因。949Please respect copyright.PENANApqx1wzA8Mz
我嘗試在PubMed拿取閻博士所指出的基因排組(藍框),並將整段S protein的基因排組(圖8)對比一下Restriction Enzyme的切割位置。949Please respect copyright.PENANAr5l6zCR5Ch949Please respect copyright.PENANAzDjNnHjeBQ
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(圖8)箇中的確發現有不同的Restriction Enzyme Site(這是非常正常的。),但並沒能找出EcoRI及BstEII的對應位置,這一點還有待閻博士解釋,需要再三認證一下她所提出的證據是否能配合所提出的質疑。949Please respect copyright.PENANAIGInM1rDS5
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(圖9)至於人工製作Polybasic Cleavage site這一點,與武肺第二相近的的RmYN02已找出與武肺類近的排組(非100%吻合, PRRA vs P-AA)。949Please respect copyright.PENANAsm5hmU3ZJv
這是大自然間的蝙蝠冠狀病毒是有著潛在能力可以擁有Polybasic cleavage site的一道跡象,絕非可以輕易漠視及完全地作出否定。949Please respect copyright.PENANAETIB0fNB5a949Please respect copyright.PENANALOtjBNJCAL
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無論如何,閻博士的見解亦有其可取及值得參考的地方,但作為直接指控病毒是實驗室製造出來的證據明顯還有一段距離,至少還有待她在文中聲稱將會發佈的另一份針對RaTG13文章才能夠下定論。949Please respect copyright.PENANAWTzmZfnON9
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Ref1:https://www.cell.com/current-biology/pdf/S0960-9822(20)30662-X.pdf949Please respect copyright.PENANA3WVLmcKL8F