學(xué)術(shù)分享

什么是病毒突變株？

病毒在進(jìn)行復(fù)制時(shí)，其遺傳物質(zhì)會(huì)發(fā)生變化，這些變化被稱為“突變”。而具有一個(gè)或多個(gè)新突變的病毒被稱為原始病毒的“變體”（即突變株）。新冠病毒作為一種分子穩(wěn)定性相對(duì)較差的RNA病毒，發(fā)生突變是再正常不過(guò)的一件事情，目前全球已經(jīng)發(fā)現(xiàn)了數(shù)百種新冠病毒的變體，其中大部分對(duì)新冠病毒的屬性影響很小甚至無(wú)影響，我們真正需要關(guān)注的是那些會(huì)影響病毒屬性的突變株。

新冠病毒的“有效”突變株主要從兩方面來(lái)影響病毒的屬性：

1）增強(qiáng)新冠病毒與宿主蛋白ACE2受體的親和力，從而增強(qiáng)病毒的感染能力；

2）幫助新冠病毒逃逸宿主免疫系統(tǒng)的攻擊，導(dǎo)致人類二次感染概率升高甚至降低疫苗有效性。

目前，尚無(wú)證據(jù)表明已知的突變點(diǎn)會(huì)增強(qiáng)新冠病毒的致病性（人感染后病情加重）。

五種重要的突變株

莫慌！核酸檢測(cè)依然靠譜

新型冠狀病毒肺炎疫情爆發(fā)以來(lái)，新冠病毒核酸檢測(cè)已經(jīng)成為群眾日常生活中司空見慣的場(chǎng)景，甚至在2021年的春節(jié)，一張核酸檢測(cè)陰性報(bào)告成為了大家回鄉(xiāng)的“車票”。當(dāng)下，越來(lái)越多新冠病毒突變株的出現(xiàn)引起了人們對(duì)于新冠核酸檢測(cè)有效性的擔(dān)憂。莫慌，筆者這就給大家排解焦慮~

依據(jù)國(guó)家新冠診療方案的要求，國(guó)內(nèi)主流的新冠檢測(cè)試劑靶標(biāo)多為ORF1ab基因和N基因，而目前發(fā)現(xiàn)的新冠突變株的“有效”突變點(diǎn)基本集中在S蛋白上，對(duì)于檢測(cè)的有效性不會(huì)造成顯著影響。此外，伯杰醫(yī)療目前亦已完成對(duì)現(xiàn)有試劑引物探針與突變株的核對(duì)，結(jié)果證實(shí)：伯杰醫(yī)療已經(jīng)上市的新型冠狀病毒2019-nCoV核酸檢測(cè)試劑盒（熒光PCR法），針對(duì)最新突變株均不會(huì)出現(xiàn)脫靶和漏檢，仍可保證檢測(cè)試劑的準(zhǔn)確性和靈敏性。

如何快速鑒別新冠突變株？

截至目前，全球已知的新冠病毒變體高達(dá)數(shù)百種，其中引人關(guān)注的B.1.1.7突變株、B.1.351突變株和P.1突變株存在的免疫逃逸現(xiàn)象已經(jīng)引起廣泛關(guān)注和討論，隱患依然存在。因而，世衛(wèi)組織及國(guó)際專家依然在密切監(jiān)測(cè)新冠病毒的變化，以便能及時(shí)發(fā)現(xiàn)重大突變，國(guó)內(nèi)也仍需投入巨大的精力監(jiān)測(cè)新冠突變株的流行情況?？磥?lái)，對(duì)于這些突變株，不該省的工序還是不能省~

當(dāng)下，全球?qū)π鹿谕蛔冎辏ㄓ绕涫俏粗蛔冎辏┑谋O(jiān)測(cè)，主要依賴基因測(cè)序技術(shù)以及全球科研人員對(duì)測(cè)序結(jié)果數(shù)據(jù)的共享。但基因測(cè)序的時(shí)間往往較長(zhǎng)，在情況緊急時(shí)，及時(shí)響應(yīng)成了一個(gè)大問(wèn)題。因而，對(duì)于已知有特異性突變點(diǎn)的突變株，我們也可以通過(guò)熒光PCR技術(shù)對(duì)突變株進(jìn)行快速鑒別分型和溯源監(jiān)測(cè)，避免貽誤疫情防控。

參考文獻(xiàn)

[1]Zhang L, Jackson C B, Mou H, et al. The D614G mutation in the SARS-CoV-2 spike protein reduces S1 shedding and increases infectivity[J]. bioRxiv, 2020.

[2]Daniloski Z, Guo X, Sanjana N, et al. The D614G mutation in SARS-CoV-2 Spike increases transduction of multiple human cell types[J]. bioRxiv, 2020.

[3] Huang AL, et al. The D614G mutation of SARS-CoV-2 spike protein enhances viral infectivity and decreases neutralization sensitivity to individual convalescent sera. bioRxiv, 2020.

[4]Fonager J., et al., Working paper on SARS-CoV-2 spike mutations arising in Danish mink, their spread to humans and neutralization data. https://files.ssi.dk/Mink-cluster-5-short-report_AFO2. 2020.

[5]van Dorp, L., et al., Recurrent mutations in SARS-CoV-2 genomes isolated from mink point to rapid host-adaptation. bioRxiv, 2020: p. 2020.11.16.384743.

[6]Starr, T.N., et al., Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals

Constraints on Folding and ACE2 Binding. Cell, 2020. 182(5): p. 1295-1310.e20.

[7]Andrew Rambaut, et al. Preliminary genomic characterisation of an emergent SARS-CoV-2 lineage in the UK defined by a novel set of spike mutations. Genomics Consortium UK (CoG-UK), December 19, 2020. Hoffmann et al. A Multibasic Cleavage Site in the Spike Protein of SARS-CoV-2 Is Essential for Infection of Human Lung Cells, 2020, Molecular Cell 78, 779–784, May 21, 2020.

[8]Gu et al. Adaptation of SARS-CoV-2 in BALB/c mice for testing vaccine efficacy, Science 369, 1603–1607 (2020).

[9]Starr et al. Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding , 2020, Cell 182, 1295–1310, September 3, 2020.

[10]Kevin R. McCarthy et al. Natural deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape. bioRxiv, December 19, 2020.

[11]Kemp SA, et al. Neutralising antibodies drive Spike mediated SARS-CoV-2 evasion. medRxiv, December 19, 2020.

[12]Thomas P. Peacock, et al. The furin cleavage site of SARS-CoV-2 spike protein is a key determinant for transmission due to enhanced replication in airway cells. bioRxiv, September 30, 2020.

[13]Yunkai Zhu, et al. The S1/S2 boundary of SARS-CoV-2 spike protein modulates cellentry pathways and transmission. bioRxiv, August 25, 2020.

[14]Houriiyah Tegally, et al.Emergence and rapid spread of a new severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa. medRxiv, December 21, 2020.

[15]Baum, A., et al., Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science, 2020: p. eabd0831.

[16]Greaney, A.J., et al., Comprehensive mapping of mutations to the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human serum antibodies. bioRxiv, 2021: p.

2020.12.31.425021.

[17]Xie, X., et al., Neutralization of N501Y mutant SARS-CoV-2 by BNT162b2 vaccine-elicited sera. bioRxiv, 2021: p. 2021.01.07.425740.

[18]Rambaut, A., et al., A dynamic nomenclature proposal for SARS-CoV-2 lineages to assist genomic epidemiology. Nature Microbiology, 2020. 5(11): p. 1403-1407.

[19]Faria, N.R., et al. Genomic characterisation of an emergent SARS-CoV-2 lineage in Manaus:

preliminary findings. 2021; Available from: https://virological.org/t/genomic-characterisation-of-anemergent-sars-cov-2-lineage-in-manaus-preliminary-findings/586.

[20]Naveca, F., et al. Phylogenetic relationship of SARS-CoV-2 sequences from Amazonas with emerging Brazilian variants harboring mutations E484K and N501Y in the Spike protein. 2021; Available from: https://virological.org/t/phylogenetic-relationship-of-sars-cov-2-sequences-from-amazonas-withemerging-brazilian-variants-harboring-mutations-e484k-and-n501y-in-the-spike-protein/585.