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应对SARS-CoV-2突变整体解决方案

背景
当前新冠疫情仍然在全球范围内肆虐,并且各地相继发现具有更强传播能力和免疫逃逸能力的新冠病毒突变株,引发国际社会的重点关注。近期,为便于向公众实时更新疫情动态,世界卫生组织(WHO)用希腊字母重新命名了几种主要的新冠病毒变异毒株,其中包括4种值得关注的新冠病毒突变株(VOCs):发现于英国的新冠病毒突变株(编号B.1.1.7)被命名为Alpha(α);发现于南非的新冠病毒突变株(编号B.1.351 )被命名为Beta(β);发现于巴西的新冠病毒突变株(编号为P.1)被命名为Gamma(γ);发现于印度的新冠病毒突变株(编号B.1.617.2)被命名为Delta (δ)。 自印度新冠疫情在4月大爆发后,具有极强传播力的Delta以惊人的速度扩散,目前已取代Alpha,成为世界上最流行新冠突变株。
除此之外还有许多其他变异株也不能忽视,例如去年 12 月在秘鲁发现的 Lambda(C.37)毒株,如今正在南美大陆上和其它多国传播,已被WHO列为“需要留意的突变株(VOIs)。按照Lambda目前的传播趋势,甚至有可能取代Delta,成为下一阶段全球流行的优势毒株。
WHO Label Pango Lineage Earliest documented samples Transmissibility Immune Evasiveness Vaccine Effectiveness
Alpha B.1.1.7 United Kingdom + + + — —
Beta B.1.351 South Africa + + + + +
Gamma P.1 Brazil + + + +
Delta B.1.617.2 India + + + + + +
LambdaC.37Peru+ + + ++ +
表1 重点突变株信息
针对全球新冠病毒主要突变株,ACROBiosystems已开发生产出一系列优质试剂产品,包括 突变抗原、抗体、ELISA试剂盒及预偶联蛋白磁珠产品,为各领域研发人员提供应对新冠病毒突变的全面解决方案。
应用场景
重要新型突变株
热门产品
重组抗原
  1. 产品覆盖热点蛋白&关键性高频突变
    Spike, RBD, S1和NTD(含K417N/T, L452R, E484K/Q, T478K, N501Y etc.); Nucleocapsid抗原(含R203G, G204 etc.)
  2. 多种标签可选择(His, Avi, Fc, mFc……)
  3. 高纯度, 高活性和良好稳定性

特色产品: 多位点突变胞外全长Spike蛋白三聚体

  • - 涵盖主要流行突变株Spike蛋白
    Alpha (Cat.No. SPN-C52H6), Beta (Cat.No. SPN-C52Hk), Gamma (Cat.No. SPN-C52Hg), Delta (Cat.No. SPN-C52He),Lambda (Cat.No. SPN-C52Hs)
  • - 覆盖多位点突变,与GISAID/Pangolin/Nextstrain数据库中真实突变株一致
  • - 引入6P突变使Spike蛋白稳定在融合前构象,可用于抑制剂药物筛选及血清滴度检测等
  • - 经SDS-PAGE和SEC-MALS验证,Spike三聚体纯度>90%
抗体
  1. 中和抗体:具备广谱中和活性,有效中和多种主流突变株
  2. 配对抗体:与所有主流突变株NP蛋白结合活性高
  3. 经ELISA验证,抗体特异性及结合活性良好
  4. 可用于诊断试剂盒开发、针对突变株的疫苗开发等

特色产品一: 经假病毒实验验证的Spike蛋白中和抗体

  • - 经假病毒实验验证,Cat.No. S1N-M122对所有VOCs突变株具有广谱中和活性,可作为中和抗体检测中的质控品

特色产品二: 经胶体金方法验证的NP蛋白配对抗体

  • - 经胶体金方法验证,配对抗体(Cat.No.NUN-M223/Cat.No.NUN-S95)可以检测出所有主流变异株的Nucleocapsid蛋白,可用于新冠抗原检测试剂盒的原料
ELISA试剂盒
  1. 产品覆盖Alpha、Beta、Gamma、delta等流行突变株
  2. 可检测中和抗体及IgG(Spike protein、Spike RBD)
  3. 采用竞争ELISA法,特异性检测中和抗体
  4. 提供实验所需的成套组分,操作简单
  5. 可同时检测90+样本,有效提升开发效率
  6. 产品稳定性及批间一致性良好

热门产品一:多种突变株中和抗体检测试剂盒

  • - 可特异性检测针对突变株的中和抗体滴度,有助于疫苗研究
  • - 原料采用高纯度、高活性的重组突变抗原蛋白
突变株种类 分子
SARS-CoV-2英国突变株 Alpha | B.1.1.7 RAS-N028
SARS-CoV-2南非突变株Beta | B.1.351 RAS-N031
SARS-CoV-2巴西突变株Gamma | P.1

RAS-N034
SARS-CoV-2 印度突变株Delta | B.1.617.2

RAS-N040 , RAS-N041
预偶联蛋白磁珠
  1. 采用生物素化标记的新冠抗原(Spike, S1, RBD等)
  2. 以链霉亲和素 (SA) 磁珠为原料,粒径均匀、比表面积大、具有超顺磁性
  3. 超高捕获效率
  4. 结果可重复性强

特色产品一:抗原偶联磁珠 (Cat.No. MBS-K029MBS-K030MBS-K031)

  • - 适用于抗体捕获/筛选,可特异性结合抗突变抗体;
  • - 可用于流式检测;

特色产品二:抗体偶联磁珠 (Cat.No. MBS-K014)

  • - 可用于结合多种不同突变株抗原;
  • - 适用于病毒富集

特色产品三:受体偶联磁珠 (Cat.No. MBS-K013)

  • - 适用于抗原检测;
流行突变株产品
  • SARS-CoV-2 南美洲突变株
    Lambda | C.37
  • SARS-CoV-2 印度突变株
    Delta | B.1.617.2
  • SARS-CoV-2英国突变株
    Alpha | B.1.1.7
  • SARS-CoV-2南非突变株
    Beta | B.1.351
  • SARS-CoV-2巴西突变株
    Gamma | P.1
  • 其它
    SARS-CoV-2热门突变株
突变位点:

L452R, F490S, G75V, T76I, SYLTPGD 247-253 del, L452Q, D614G, T859N

标签:

His Tag;His Tag & Avi Tag

抗原表位:

Spike protein, Spike RBD

相关产品:

突变抗原

突变位点:

S蛋白突变:T19R, G142D, EF156-157del, R158G, L452R, T478K, D614G, P681R, D950N;
N蛋白突变:D63G, R203M, D377Y

标签:

His Tag;His Tag & Avi Tag

抗原表位:

Spike protein, Spike S1, Spike RBD, Spike NTD, Nucleocapsid protein

相关产品:

突变抗原ELISA试剂盒

突变位点:

S蛋白突变:HV69-70del, Y144del, N501Y, A570D, D614G, P681H, T716I, S982A, D1118H;
N蛋白突变:D3L, R203K, G204R, S235F;

标签:

His Tag;His Tag & Avi Tag;Fc tag

抗原表位:

Spike protein, Spike S1, Spike RBD, Spike NTD, Spike S2, Nucleocapsid protein etc.

相关产品:

突变抗原中和抗体ELISA试剂盒预偶联磁珠

突变位点:

S蛋白突变:L18F, D80A, D215G, 242-244del, R246I, K417N, E484K, N501Y, D614G, A701V;
N蛋白突变:T205I;

标签:

His Tag;His Tag & Avi Tag;Fc tag;mFc tag

抗原表位:

Spike protein, Spike S1, Spike RBD, Spike NTD, Spike S2, Nucleocapsid protein

相关产品:

突变抗原中和抗体ELISA试剂盒预偶联磁珠

突变位点:

S蛋白突变:L18F, T20N, P26S, D138Y, R190S, K417T, E484K, N501Y, D614G, H655Y, T1027I, V1176F;
N蛋白突变:P80R;

标签:

His Tag;His Tag & Avi Tag;Fc tag;mFc tag

抗原表位:

Spike protein, Spike S1, Spike RBD, Spike NTD, Spike S2, Nucleocapsid protein

相关产品:

突变抗原中和抗体ELISA试剂盒预偶联磁珠

<<< 如果您希望ACRO开发更多类型的新冠病毒突变产品,请点击提议

<<<  点击查看所有新冠相关产品

应用场景 & 验证数据
新冠病毒传染性和致病性机理研究——检测突变株RBD抗原与受体ACE2的亲和力

经SPR验证,ACE2与Alpha/Beta/Gamma突变株的结合亲和力与野生型RBD比较,均相差一个数量级,KD值均为nM水平。表明RBD突变体和ACE2的结合亲和力增强,可能是导致Alpha, Beta, Gamma突变株感染力增加的原因。

图1. SPR方法检测ACE2 (Cat. No. AC2-H52H8)分别与WT RBD (Cat.No. SPD-C52H3) (KD=1.03E-08M) (左上)、Alpha突变株RBD(Cat.No. SPD-C52Hn)(KD=1.24E-09M)(右上)、Beta突变株RBD(Cat.No. SPD-C52Hp)(KD=3.27E-09 M)(左下)、Gamma突变株RBD(Cat.No. SPD-C52Hr)( KD=2.23E-09M)(右下)的亲和力比较

Protocol

疫苗免疫应答检测——检测中和抗体滴度,测试突变株对抗体效力的影响
a. 突变株中和抗体滴度检测试剂盒

经检测,接种灭活疫苗的血清样本对Wild type和B.1.1.7变异株的中和能力接近,但对B.1.351和P.1毒株的中和能力明显下降。

图 2. 新冠病毒(突变株)中和抗体滴度检测试剂盒检测56份接种灭活疫苗后的血清样本中的中和抗体滴度。血清样本中的中和抗体对野生型和B.1.1.7突变株的中和能力接近,但对B.1.351和P.1突变株的中和能力明显下降。(图中产品分别对应WT-RBD(Cat. No. RAS-N022),B.1.1.7 RBD(Cat. No. RAS-N028),B.1.351 RBD(Cat. No. RAS-N031),P.1 RBD(Cat. No. RAS-N034

Protocol

b. 广谱型中和抗体(质控品)

经假病毒实验体系验证,广谱型中和抗体(Cat.No. S1N-M122) 可以有效中和野生型及Alpha/Beta/Gamma/Delta突变株病毒,适合作为质控品,应用于针对突变株的中和抗体筛选、重组蛋白疫苗研发、疫苗接种后血清中的中和抗体检测等。

图3. 新冠广谱中和抗体(Cat.No. S1N-M122)对野生型和各种突变Spike RBD的中和活性

Protocol

抑制剂药物筛选——筛选对突变株有效的小分子药物/高中和活性的广谱型中和抗体
a. 抑制剂筛选试剂盒

使用抑制剂筛选试剂盒(Cat.No. EP-105)经抗体筛选实验,获得多株具有中和能力的抗体候选物,且经P3实验室验证可以有效中和新冠病毒对Vero细胞的感染。表明SARS-CoV-2抑制剂筛选试剂盒和新冠病毒中和实验两者之间具有很好的相关性,有助于快速地筛选和验证药物,提高药物开发效率。

图4. 使用SARS-CoV-2抑制剂筛选试剂盒(Cat.No. EP-105)对多个血液来源的抗体候选物进行中和筛选。

Protocol

b. 预偶联突变抗原磁珠

经验证,偶联突变体的磁珠具有稳定性好、低非特异性结合、便捷高效的特点,能够节约实验的时间成本,提升抗体筛选效率。

图5. 预偶联新冠B.1.1.7突变株Spike Trimer的磁珠(Cat.No. MBS-K029)和Anti-SARS-CoV-2 S1抗体的结合曲线表明,该磁珠可以很好地捕获抗体。预偶联蛋白载量>24 μg/mg磁珠,捕获抗体载量>23 μg/mg磁珠。

Protocol

新冠诊断试剂盒开发——验证配对抗体/抗原检测试剂能否识别突变株
a. 抗S抗原配对抗体

经验证,靶向新冠病毒RBD区域的配对抗体(Cat.No. S1N-M12A1/S1N-M13A1)灵敏度高,特异性好;可用于新冠病毒S抗原检测试剂盒开发。

图6. 双抗体夹心法检测突变RBD蛋白(Cat.No. SPD-C52Hn; SRD-C52H3; SPD-C52Hp

Protocol

b. 抗N抗原配对抗体

经ELISA验证,配对N抗体原料(Cat.No. NUN-M223/NUN-S95)能够识别所有实验中检测的突变N抗原,可用于新冠N抗原检测试剂盒开发。

标记抗体AS95(Cat.No. NUN-S95)与各种突变N蛋白结合亲和力强

Protocol

包被抗体AM223(Cat.No. NUN-M223)与各种突变N蛋白结合亲和力强

Protocol

<<<点击查看新冠病毒与宿主细胞互作图

前沿进展
  • First identification of SARS-CoV-2 Lambda (C.37) variant in Southern Brazil

    Priscila Lamb Wink PhD, Fabiana Caroline Zempulski Volpato MSc, Francielle Liz Monteiro PhD, et.al

    doi:https://doi.org/10.1101/2021.06.21.21259241

    Abstract: In June 15, 2021, the lineage Lambda (C.37) of SARS-CoV-2 was considered a variant of interest (VOI) by the World Health Organization. This lineage has high prevalence in some South America countries but it was described only occasionally in Brazil. Here we describe the first report of the SARS-CoV-2 Lambda variant in Southern Brazil. The sequence described in this paper presented all the eight C.37 defining lineage mutations (ORF1a gene: Δ3675-3677; Spike gene: Δ246-252, G75V, T76I, L452Q, F490S, D614G, and T859N) in addition to other 19 mutations. Considering that this VOI has been associated with high rates of transmissibility, the possible spread in the Southern Brazilian community is a matter of concern.
    展开 

  • Infectivity and immune escape of the new SARS-CoV-2 variant of interest Lambda

    Mónica L. Acevedo, Luis Alonso-Palomares, Andrés Bustamante, et.al

    doi:https://doi.org/10.1101/2021.06.28.21259673

    Background: The newly described SARS-CoV-2 lineage C.37 was recently classified as a variant of interest by the WHO (Lambda variant) based on its high circulation rates in South American countries and the presence of critical mutations in the spike protein. The impact of such mutations in infectivity and immune escape from neutralizing antibodies are entirely unknown.
    Methods: We performed a pseudotyped virus neutralization assay and determined the impact of the Lambda variant on infectivity and immune escape using plasma samples from healthcare workers (HCW) from two centers in Santiago, Chile who received the two-doses scheme of the inactivated virus vaccine CoronaVac.
    Results: We observed an increased infectivity mediated by the Lambda spike protein that was even higher than that of the D614G (lineage B) or the Alpha and Gamma variants. Compared to the Wild type (lineage A), neutralization was decreased by 3.05-fold for the Lambda variant while it was 2.33-fold for the Gamma variant and 2.03-fold for the Alpha variant.
    Conclusions: Our results indicate that mutations present in the spike protein of the Lambda variant of interest confer increased infectivity and immune escape from neutralizing antibodies elicited by CoronaVac. These data reinforce the idea that massive vaccination campaigns in countries with high SARS-CoV-2 circulation must be accompanied by strict genomic surveillance allowing the identification of new isolates carrying spike mutations and immunology studies aimed to determine the impact of these mutations in immune escape and vaccines breakthrough.
    展开 

  • SARS-CoV-2 Lambda variant exhibits higher infectivity and immune resistance

    Izumi Kimura, Yusuke Kosugi, Jiaqi Wu, et.al

    doi:https://doi.org/10.1101/2021.07.28.454085

    Abstract: SARS-CoV-2 Lambda, a new variant of interest, is now spreading in some South American countries; however, its virological features and evolutionary trait remain unknown. Here we reveal that the spike protein of the Lambda variant is more infectious and it is attributed to the T76I and L452Q mutations. The RSYLTPGD246-253N mutation, a unique 7-amino-acid deletion mutation in the N-terminal domain of the Lambda spike protein, is responsible for evasion from neutralizing antibodies. Since the Lambda variant has dominantly spread according to the increasing frequency of the isolates harboring the RSYLTPGD246-253N mutation, our data suggest that the insertion of the RSYLTPGD246-253N mutation is closely associated with the massive infection spread of the Lambda variant in South America.
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  • SARS-CoV-2 Lambda Variant Remains Susceptible to Neutralization by mRNA Vaccine-elicited Antibodies and Convalescent Serum

    Takuya Tada, Hao Zhou, Belinda M. Dcosta, et.al

    doi:https://doi.org/10.1101/2021.07.02.450959

    Abstract: The SARS-CoV-2 lambda variant (lineage C.37) was designated by the World Health Organization as a variant of interest and is currently increasing in prevalence in South American and other countries. The lambda spike protein contains novel mutations within the receptor binding domain (L452Q and F490S) that may contribute to its increased transmissibility and could result in susceptibility to re-infection or a reduction in protection provided by current vaccines. In this study, the infectivity and susceptibility of viruses with the lambda variant spike protein to neutralization by convalescent sera and vaccine elicited antibodies was tested. Virus with the lambda spike had higher infectivity and was neutralized by convalescent sera and vaccine-elicited antibodies with a relatively minor 2.3-3.3-fold decrease in titer on average. The virus was neutralized by the Regeneron therapeutic monoclonal antibody cocktail with no loss of titer. The results suggest that vaccines in current use will remain protective against the lambda variant and that monoclonal antibody therapy will remain effective.
    展开 

  • Surveillance of SARS-CoV-2 variants in Argentina: detection of Alpha, Gamma, Lambda, Epsilon and Zeta in locally transmitted and imported cases

    Torres Carolina, Mojsiejczuk Laura, Acuña Dolores, et.al

    doi:https://doi.org/10.1101/2021.07.19.21260779

    Abstract: Molecular surveillance of SARS-CoV-2 variants was performed on a total of 2,406 samples from the capital city and nine provinces of Argentina, during 30 epidemiological weeks (EW) that covered the end of the first wave and the beginning of the ongoing second wave of the COVID-19 pandemic in the country (EW 44/2020 to EW 20/2021). The surveillance strategy was mainly based on Sanger sequencing of a Spike coding region that allows the simultaneous identification of signature mutations associated with worldwide circulating variants. In addition, whole SARS-CoV-2 genome sequences were obtained from 456 samples. The main variants found were Gamma, Lambda and Alpha, and to a lesser extent, Zeta and Epsilon. Whereas Gamma dominated in different regions of the country, both Gamma and Lambda prevailed in the most populated area, the metropolitan region of Buenos Aires (MABA), although showing a heterogeneous distribution along this region. This cost-effective surveillance protocol allowed for a rapid response in a limited access to resources scenario, added information on the expansion of the Lambda variant in South America and contributed to the implementation of public health measures to control the disease spread in Argentina.
    展开 

  • THE EMERGENCE OF SARS-COV-2 VARIANT LAMBDA (C.37) IN SOUTH AMERICA

    Pedro E. Romeroa, Alejandra Dávila-Barclay, Guillermo Salvatierra, et.al

    doi:https://doi.org/10.1101/2021.06.26.21259487

    Abstract: We report the emergence of a novel lineage of SARS-CoV-2 in South America, termed C.37. It presents seven nonsynonymous mutations in the Spike gene (Δ247-253, G75V, T76I, L452Q, F490S, T859N) and a deletion in the ORF1a gene (Δ3675-3677) also found in variants of concern (VOCs) Alpha, Beta, and Gamma. Initially reported in Lima, Peru, in late December 2020, it now accounts for 97% of Peruvian public genomes in April 2021. It is expanding in Chile and Argentina, and there is evidence of onward transmission in Colombia, Ecuador, Mexico, the USA, Germany, and Israel. On June 15, 2021, the World Health Organization designated C.37 as Variant of Interest (VOI) Lambda.
    more  

  • Rapid displacement of SARS-CoV-2 variant B.1.1.7 by B.1.617.2 and P.1 in the United States

    Alexandre Bolze, Elizabeth T. Cirulli, Shishi Luo, et.al

    doi: https://doi.org/10.1101/2021.06.20.21259195

    The SARS-CoV-2 variant of concern B.1.617.2 displaced B.1.1.7 as the dominant variant in England and other countries. This study aimed to determine whether B.1.617.2 was also displacing B.1.1.7 in the United States. We analyzed PCR testing results and viral sequencing results of samples collected across the United States, and showed that B.1.1.7 was rapidly being displaced and is no longer responsible for the majority of new cases. The percentage of SARS-CoV-2 positive cases that are B.1.1.7 dropped from 70% in April 2021 to 42% in just 6 weeks. Our analysis showed rapid growth of variants B.1.617.2 and P.1 as the primary drivers for this displacement. Currently, the growth rate of B.1.617.2 was higher than P.1 in the US (0.61 vs. 0.22), which is consistent with reports from other countries. Lastly, we showed that B.1.617.2 was growing faster in counties with a lower vaccination rate.

  • Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum

    Chang Liu, Helen M. Ginn, Wanwisa Dejnirattisai, Piyada Supasa, Beibei Wang, et.al

    doi: https://doi.org/10.1016/j.cell.2021.06.020

    SARS-CoV-2 has undergone progressive change with variants conferring advantage rapidly becoming dominant lineages e.g. B.1.617. With apparent increased transmissibility variant B.1.617.2 has contributed to the current wave of infection ravaging the Indian subcontinent and has been designated a variant of concern in the UK. Here we study the ability of monoclonal antibodies, convalescent and vaccine sera to neutralize B.1.617.1 and B.1.617.2 and complement this with structural analyses of Fab/RBD complexes and map the antigenic space of current variants. Neutralization of both viruses is reduced when compared with ancestral Wuhan related strains but there is no evidence of widespread antibody escape as seen with B.1.351. However, B.1.351 and P.1 sera showed markedly more reduction in neutralization of B.1.617.2 suggesting that individuals previously infected by these variants may be more susceptible to reinfection by B.1.617.2. This observation provides important new insight for immunisation policy with future variant vaccines in non-immune populations.

  • SARS-CoV-2 variant B.1.617 is resistant to Bamlanivimab and evades antibodies induced by infection and vaccination

    Markus Hoffmann, Heike Hofmann-Winkler, Nadine Krüger, et.al

    doi: https://doi.org/10.1101/2021.05.04.442663

    Abstract: The emergence of SARS-CoV-2 variants threatens efforts to contain the COVID-19 pandemic. The number of COVID-19 cases and deaths in India has risen steeply in recent weeks and a novel SARS-CoV-2 variant, B.1.617, is believed to be responsible for many of these cases. The spike protein of B.1.617 harbors two mutations in the receptor binding domain, which interacts with the ACE2 receptor and constitutes the main target of neutralizing antibodies. Therefore, we analyzed whether B.1.617 is more adept in entering cells and/or evades antibody responses. B.1.617 entered two out of eight cell lines tested with slightly increased efficiency and was blocked by entry inhibitors. In contrast, B.1.617 was resistant against Bamlanivimab, an antibody used for COVID-19 treatment. Finally, B.1.617 evaded antibodies induced by infection or vaccination, although with moderate efficiency. Collectively, our study reveals that antibody evasion of B.1.617 may contribute to the rapid spread of this variant.

  • SARS-CoV-2 variant B.1.617 is resistant to Bamlanivimab and evades antibodies induced by infection and vaccination

    Markus Hoffmann, Heike Hofmann-Winkler, Nadine Krüger, et.al

    doi: https://doi.org/10.1101/2021.05.04.442663

    Abstract: The emergence of SARS-CoV-2 variants threatens efforts to contain the COVID-19 pandemic. The number of COVID-19 cases and deaths in India has risen steeply in recent weeks and a novel SARS-CoV-2 variant, B.1.617, is believed to be responsible for many of these cases. The spike protein of B.1.617 harbors two mutations in the receptor binding domain, which interacts with the ACE2 receptor and constitutes the main target of neutralizing antibodies. Therefore, we analyzed whether B.1.617 is more adept in entering cells and/or evades antibody responses. B.1.617 entered two out of eight cell lines tested with slightly increased efficiency and was blocked by entry inhibitors. In contrast, B.1.617 was resistant against Bamlanivimab, an antibody used for COVID-19 treatment. Finally, B.1.617 evaded antibodies induced by infection or vaccination, although with moderate efficiency. Collectively, our study reveals that antibody evasion of B.1.617 may contribute to the rapid spread of this variant.

  • Possible link between higher transmissibility of B.1.617 and B.1.1.7 variants of SARS-CoV-2 and increased structural stability of its spike protein and hACE2 affinity

    Vipul Kumar1, Jasdeep Singh, Seyed E. Hasnain, Durai Sundar

    doi: https://doi.org/10.1101/2021.04.29.441933

    Abstract: The Severe Acute syndrome corona Virus 2 (SARS-CoV-2) outbreak in December 2019 has caused a global pandemic. The rapid mutation rate in the virus has caused alarming situations worldwide and is being attributed to the false negativity in RT-PCR tests, which also might lead to inefficacy of the available drugs. It has also increased the chances of reinfection and immune escape. We have performed Molecular Dynamic simulations of three different Spike-ACE2 complexes, namely Wildtype (WT), B.1.1.7 variant (N501Y Spike mutant) and B.1.617 variant (L452R, E484Q Spike mutant) and compared their dynamics, binding energy and molecular interactions. Our result shows that mutation has caused the increase in the binding energy between the Spike and hACE2. In the case of B.1.617 variant, the mutations at L452R and E484Q increased the stability and intra-chain interactions in the Spike protein, which may change the interaction ability of human antibodies to this Spike variant. Further, we found that the B.1.1.7 variant had increased hydrogen interaction with LYS353 of hACE2 and more binding affinity in comparison to WT. The current study provides the biophysical basis for understanding the molecular mechanism and rationale behind the increase in the transmissivity and infectivity of the mutants compared to wild-type SARS-CoV-2.

  • Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees

    Pragya D. Yadav, Gajanan N. Sapkal, Priya Abraham, M.D

    doi: https://doi.org/10.1101/2021.04.23.441101

    Abstract: The drastic rise in the number of cases in Maharashtra, India has created a matter of concern for public health experts. Twelve isolates of VUI lineage B.1.617 were propagated in VeroCCL81 cells and characterized. Convalescent sera of the COVID-19 cases and recipients of BBV152 (Covaxin) were able to neutralize VUI B.1.617.

  • Convergent evolution of SARS-CoV-2 spike mutations, L452R, E484Q and P681R, in the second wave of COVID-19 in Maharashtra, India

    Sarah Cherian, Varsha Potdar, Santosh Jadhav, et al.

    doi: https://doi.org/10.1101/2021.04.22.440932

    Abstract: As the global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic expands, genomic epidemiology and whole genome sequencing are being constantly used to investigate its transmissions and evolution. In the backdrop of the global emergence of “variants of concern” (VOCs) during December 2020 and an upsurge in a state in the western part of India since January 2021, whole genome sequencing and analysis of spike protein mutations using sequence and structural approaches was undertaken to identify possible new variants and gauge the fitness of current circulating strains. Phylogenetic analysis revealed that the predominant clade in circulation was a distinct newly identified lineage B.1.617 possessing common signature mutations D111D, G142D, L452R, E484Q, D614G and P681R, in the spike protein including within the receptor binding domain (RBD). Of these, the mutations at residue positions 452, 484 and 681 have been reported in other globally circulating lineages. The structural analysis of RBD mutations L452R and E484Q along with P681R in the furin cleavage site, may possibly result in increased ACE2 binding and rate of S1-S2 cleavage resulting in better transmissibility. The same two RBD mutations indicated decreased binding to selected monoclonal antibodies (mAbs) and may affect their neutralization potential. Experimental validation is warranted for accessing both ACE2 binding and the effectiveness of commonly elicited neutralizing mAbs for the strains of lineage B.1.617. The emergence of such local variants through the accumulation of convergent mutations during the COVID-19 second wave needs to be further investigated for their public health impact in the rest of the country and its possibility of becoming a VOC.

  • Bioinformatics analysis of SARS-CoV-2 RBD mutant variants and insights into antibody and ACE2 receptor binding

    Prashant Ranjan, Neha, Chandra Devi1and Parimal Das

    doi: https://doi.org/10.1101/2021.04.03.438113

    Abstract: Prevailing COVID-19 vaccines are based on the spike protein of earlier SARS-CoV-2 strain that emerged in Wuhan, China. Continuously evolving nature of SARS-CoV-2 resulting emergence of new variant/s raise the risk of immune absconds. Several RBD (receptor-binding domain) variants have been reported to affect the vaccine efficacy considerably. In the present study, we performed in silico structural analysis of spike protein of double mutant (L452R & E484Q), a new variant of SARS-CoV-2 recently reported in India along with K417G variants and earlier reported RBD variants and found structural changes in RBD region after comparing with the wild type. Comparison of the binding affinity of the double mutant and earlier reported RBD variant for ACE2 (angiotensin 2 altered enzymes) receptor and CR3022 antibody with the wildtype strain revealed the lowest binding affinity of the double mutant for CR3022 among all other variants. These findings suggest that the newly emerged double mutant could significantly reduce the impact of the current vaccine which threatens the protective efficacy of current vaccine therapy.

  • Antibody Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7

    Pengfei Wang, Manoj S. Nair, Lihong Liu et al

    doi: https://doi.org/10.1101/2021.01.25.428137

    Abstract: The COVID-19 pandemic has ravaged the globe, and its causative agent, SARS-CoV-2, continues to rage. Prospects of ending this pandemic rest on the development of effective interventions. Single and combination monoclonal antibody(mAb) therapeutics have received emergency use authorization, with more in the pipeline. Furthermore, multiple vaccine constructs have shown promise8, including two with ~95% protective efficacy against COVID-19. However, these interventions were directed toward the initial SARS-CoV-2 that emerged in 2019. The recent emergence of new SARS-CoV-2 variants B.1.1.7 in the UK and B.1.351 in South Africa is of concern because of their purported ease of transmission and extensive mutations in the spike protein. We now report that B.1.1.7 is refractory to neutralization by most mAbs to the N-terminal domain (NTD) of spike and relatively resistant to a few mAbs to the receptor-binding domain (RBD). It is not more resistant to convalescent plasma or vaccinee sera. Findings on B.1.351 are more worrisome in that this variant is not only refractory to neutralization by most NTD mAbs but also by multiple individual mAbs to the receptor-binding motif on RBD, largely due to an E484K mutation. Moreover, B.1.351 is markedly more resistant to neutralization by convalescent plasma (9.4 fold) and vaccinee sera (10.3-12.4 fold). B.1.351 and emergent variants with similar spike mutations present new challenges for mAb therapy and threaten the protective efficacy of current vaccines.

  • SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma

    Constantinos Kurt Wibmer, Frances Ayres, Tandile Hermanus et al

    doi: https://doi.org/10.1101/2021.01.18.427166

    Abstract: SARS-CoV-2 501Y.V2, a novel lineage of the coronavirus causing COVID-19, contains multiple mutations within two immunodominant domains of the spike protein. Here we show that this lineage exhibits complete escape from three classes of therapeutically relevant monoclonal antibodies. Furthermore 501Y.V2 shows substantial or complete escape from neutralizing antibodies in COVID-19 convalescent plasma. These data highlight the prospect of reinfection with antigenically distinct variants and may foreshadow reduced efficacy of current spike-based vaccines.

  • Comprehensive mapping of mutations to the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human serum antibodies

    Allison J. Greaney, Andrea N. Loes, Katharine H.D. Crawford et al

    doi: https://doi.org/10.1101/2020.12.31.425021

    Abstract: The evolution of SARS-CoV-2 could impair recognition of the virus by human antibody-mediated immunity. To facilitate prospective surveillance for such evolution, we map how convalescent serum antibodies are impacted by all mutations to the spike’s receptor-binding domain (RBD), the main target of serum neutralizing activity. Binding by polyclonal serum antibodies is affected by mutations in three main epitopes in the RBD, but there is substantial variation in the impact of mutations both among individuals and within the same individual over time. Despite this inter- and intra-person heterogeneity, the mutations that most reduce antibody binding usually occur at just a few sites in the RBD’s receptor binding motif. The most important site is E484, where neutralization by some sera is reduced >10-fold by several mutations, including one in emerging viral lineages in South Africa and Brazil. Going forward, these serum escape maps can inform surveillance of SARS-CoV-2 evolution.

  • Transmission of SARS-CoV-2 Lineage B.1.1.7 in England: Insights from linking epidemiological and genetic data

    Volz, Mishra*, Chand et al

    doi: https://doi.org/10.1101/2020.12.30.20249034

    Abstract: The SARS-CoV-2 lineage B.1.1.7, now designated Variant of Concern 202012/01 (VOC) by Public Health England, originated in the UK in late Summer to early Autumn 2020. We examine epidemiological evidence for this VOC having a transmission advantage from several perspectives. First, whole genome sequence data collected from community-based diagnostic testing provides an indication of changing prevalence of different genetic variants through time. Phylodynamic modelling additionally indicates that genetic diversity of this lineage has changed in a manner consistent with exponential growth. Second, we find that changes in VOC frequency inferred from genetic data correspond closely to changes inferred by S-gene target failures (SGTF) in community-based diagnostic PCR testing. Third, we examine growth trends in SGTF and non-SGTF case numbers at local area level across England, and show that the VOC has higher transmissibility than non-VOC lineages, even if the VOC has a different latent period or generation time. Available SGTF data indicate a shift in the age composition of reported cases, with a larger share of under 20 year olds among reported VOC than non-VOC cases. Fourth, we assess the association of VOC frequency with independent estimates of the overall SARS-CoV-2 reproduction number through time. Finally, we fit a semi-mechanistic model directly to local VOC and non-VOC case incidence to estimate the reproduction numbers over time for each. There is a consensus among all analyses that the VOC has a substantial transmission advantage, with the estimated difference in reproduction numbers between VOC and non-VOC ranging between 0.4 and 0.7, and the ratio of reproduction numbers varying between 1.4 and 1.8. We note that these estimates of transmission advantage apply to a period where high levels of social distancing were in place in England; extrapolation to other transmission contexts therefore requires caution.

  • Estimated transmissibility and severity of novel SARS-CoV-2 Variant of Concern 202012/01 in England

    Davies, Barnard, Jarvis et al

    doi: https://doi.org/10.1101/2020.12.24.20248822

    Abstract: A novel SARS-CoV-2 variant, VOC 202012/01, emerged in southeast England in November 2020 and appears to be rapidly spreading towards fixation. We fitted a two-strain mathematical model of SARS-CoV-2 transmission to observed COVID-19 hospital admissions, hospital and ICU bed occupancy, and deaths; SARS-CoV-2 PCR prevalence and seroprevalence; and the relative frequency of VOC 202012/01 in the three most heavily affected NHS England regions (South East, East of England, and London). We estimate that VOC 202012/01 is 56% more transmissible (95% credible interval across three regions 50-74%) than preexisting variants of SARS-CoV-2. We were unable to find clear evidence that VOC 202012/01 results in greater or lesser severity of disease than preexisting variants. Nevertheless, the increase in transmissibility is likely to lead to a large increase in incidence, with COVID-19 hospitalisations and deaths projected to reach higher levels in 2021 than were observed in 2020, even if regional tiered restrictions implemented before 19 December are maintained. Our estimates suggest that control measures of a similar stringency to the national lockdown implemented in England in November 2020 are unlikely to reduce the effective reproduction number Rt to less than 1, unless primary schools, secondary schools, and universities are also closed. We project that large resurgences of the virus are likely to occur following easing of control measures. It may be necessary to greatly accelerate vaccine roll-out to have an appreciable impact in suppressing the resulting disease burden.

  • Early empirical assessment of the N501Y mutant strains of SARS-CoV-2 in the United Kingdom, October to November 2020

    Leung, Shum, Leung et al

    doi: https://doi.org/10.1101/2020.12.20.20248581

    Abstract: Two new SARS-CoV-2 lineages with the N501Y mutation in the receptor binding domain of the spike protein have rapidly become prevalent in the UK. We estimated that the earlier 501Y lineage without amino acid deletion Δ69/Δ70 circulating mainly between early September to mid-November was 10% (6-13%) more transmissible than the 501N lineage, and the currently dominant 501Y lineage with amino acid deletion Δ69/Δ70 circulating since late September was 75% (70-80%) more transmissible than the 501N lineage.

  • Mutation Landscape of SARS-CoV-2 in Africa

    Nassir, Musanabaganwa, Mwikarago

    doi: https://doi.org/10.1101/2020.12.20.423630

    Abstract: COVID-19 disease has had a relatively less severe impact in Africa. To understand the role of SARS CoV2 mutations on COVID-19 disease in Africa, we analysed 282 complete nucleotide sequences from African isolates deposited in the NCBI Virus Database. Sequences were aligned against the prototype Wuhan sequence (GenBank accession: NC_045512.2) in BWA v. 0.7.17. SAM and BAM files were created, sorted and indexed in SAMtools v. 1.10 and marked for duplicates using Picard v. 2.23.4. Variants were called with mpileup in BCFtools v. 1.11. Phylograms were created using Mr. Bayes v 3.2.6. A total of 2,349 single nucleotide polymorphism (SNP) profiles across 294 sites were identified. Clades associated with severe disease in the United States, France, Italy, and Brazil had low frequencies in Africa (L84S=2.5%, L3606F=1.4%, L3606F/V378I/=0.35, G251V=2%). Sub Saharan Africa (SSA) accounted for only 3% of P323L and 4% of Q57H mutations in Africa. Comparatively low infections in SSA were attributed to the low frequency of the D614G clade in earlier samples (25% vs 67% global). Higher disease burden occurred in countries with higher D614G frequencies (Egypt=98%, Morocco=90%, Tunisia=52%, South Africa) with D614G as the first confirmed case. V367F, D364Y, V483A and G476S mutations associated with efficient ACE2 receptor binding and severe disease were not observed in Africa. 95% of all RdRp mutations were deaminations leading to CpG depletion and possible attenuation of virulence. More genomic and experimental studies are needed to increase our understanding of the temporal evolution of the virus in Africa, clarify our findings, and reveal hot spots that may undermine successful therapeutic and vaccine interventions.

  • Major new lineages of SARS-CoV-2 emerge and spread in South Africa during lockdown

    Tegally, Wilkinson, Lessells et al

    doi: https://www.medrxiv.org/content/10.1101/2020.10.28.20221143v1

    Abstract: In March 2020, the first cases of COVID-19 were reported in South Africa. The epidemic spread very fast despite an early and extreme lockdown and infected over 600,000 people, by far the highest number of infections in an African country. To rapidly understand the spread of SARS-CoV-2 in South Africa, we formed the Network for Genomics Surveillance in South Africa (NGS-SA). Here, we analyze 1,365 high quality whole genomes and identify 16 new lineages of SARS-CoV-2. Most of these unique lineages have mutations that are found hardly anywhere else in the world. We also show that three lineages spread widely in South Africa and contributed to ∼42% of all of the infections in the country. This included the first identified C lineage of SARS-CoV-2, C.1, which has 16 mutations as compared with the original Wuhan sequence. C.1 was the most geographically widespread lineage in South Africa, causing infections in multiple provinces and in all of the eleven districts in KwaZulu-Natal (KZN), the most sampled province. Interestingly, the first South-African specific lineage, B.1.106, which was identified in April 2020, became extinct after nosocomial outbreaks were controlled. Our findings show that genomic surveillance can be implemented on a large scale in Africa to identify and control the spread of SARS-CoV-2.

  • 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

    Tegally, Wilkinson, Giovanetti et al

    doi: https://doi.org/10.1101/2020.12.21.20248640

    Summary: Continued uncontrolled transmission of the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) in many parts of the world is creating the conditions for significant virus evolution. Here, we describe a new SARS-CoV-2 lineage (501Y.V2) characterised by eight lineage-defining mutations in the spike protein, including three at important residues in the receptor-binding domain (K417N, E484K and N501Y) that may have functional significance. This lineage emerged in South Africa after the first epidemic wave in a severely affected metropolitan area, Nelson Mandela Bay, located on the coast of the Eastern Cape Province. This lineage spread rapidly, becoming within weeks the dominant lineage in the Eastern Cape and Western Cape Provinces. Whilst the full significance of the mutations is yet to be determined, the genomic data, showing the rapid displacement of other lineages, suggest that this lineage may be associated with increased transmissibility.

  • Early transmission of SARS-CoV-2 in South Africa: An epidemiological and phylogenetic report

    Giandharia, Pillaya, Wilkinson et al

    Int J Infect Dis(2020)11, 128

    doi: https://doi.org/10.1016/j.ijid.2020.11.128

    Abstract: Objectives: The Network for Genomic Surveillance in South Africa (NGS-SA) was formed to investigate the introduction and understand the early transmission dynamics of the SARS-CoV-2 epidemic in South-Africa.
    Design: This paper presents the first results from this group, which is a molecular epidemiological study of the first 21 SARS-CoV-2 whole genomes sampled in the first port of entry – KwaZulu-Natal (KZN) –during the first month of the epidemic. By combining this with calculations of the effective reproduction number (R), it aimed to shed light on the patterns of infections in South Africa.
    Results: Two of the largest provinces – Gauteng and KZN – had a slow growth rate for the number of detected cases, while the epidemic spread faster in the Western Cape and Eastern Cape. The estimates of transmission potential suggested a decrease towards R = 1 since the first cases and deaths, but a subsequent estimated R average of 1.39 between 6–18 May 2020. It was also demonstrated that early transmission in KZN was associated with multiple international introductions and dominated by lineages B1 and B. Evidence for locally acquired infections in a hospital in Durban within the first month of the epidemic was also provided.
    Conclusion: The COVID-19 pandemic in South Africa was very heterogeneous in its spatial dimension, with many distinct introductions of SARS-CoV2 in KZN and evidence of nosocomial transmission, which inflated early mortality in KZN. The epidemic at the local level was still developing and NGS-SA aimed to clarify the dynamics in South Africa and devise the most effective measures as the outbreak evolved.

  • Brief report: New Variant Strain of SARS-CoV-2 Identified in Travelers from Brazil

    January 12, 2021

    National Institute of Infectious Diseases, JAPAN

    Technical detail: The variant isolate (GISAID ID: EPI_ISL_792680 to 792683) belongs to B.1.1.248 lineage and has 12 mutations in the spike protein, including N501Y and E484K. - N501Y is a mutation found in variant strains including VOC-202012/01 and 501Y.V2, implicated to increase transmissibility. - The E484K was reported to be an escape mutation from a monoclonal antibody which neutralize SARSCoV-2 (1,2). The E484K has been observed in variant isolates escaping from convalescent plasma (3) and with a 10-fold decrease in neutralization capability by convalescent plasma (4)(both in preprint articles), suggesting possible change in antigenicity. - In Brazil, a variant isolate with E484K belonging to B.1.1.248 was reported on January 6, 2021 (5), but it is not identical to the new variant isolate identified in Japan.

  • Researchers Discover New Variant of COVID-19 Virus in Columbus, Ohio

    January 13, 2021

    The Ohio State University Wexner Medical Center

    Scientists at The Ohio State University Wexner Medical Center and College of Medicine have discovered a new variant of SARS-Cov-2, the virus that causes COVID-19. The new variant carries a mutation identical to the U.K. strain, but it likely arose in a virus strain already present in the United States. The researchers also report the evolution of another U.S. strain that acquired three other gene mutations not previously seen together in SARS-CoV2.

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