Emergent SARS-CoV-2 variants: comparative replication dynamics and high sensitivity to thapsigargin.
Emergent SARS-CoV-2 variants: comparative replication dynamics and high sensitivity to thapsigargin.
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DOI：
10.1080/21505594.2021.2006960
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发表时间：
2021-12
期刊：
影响因子：
5.2
通讯作者：
Chang KC
中科院分区：
文献类型：
--
作者：
Al-Beltagi S;Goulding LV;Chang DKE;Mellits KH;Hayes CJ;Gershkovich P;Coleman CM;Chang KC
由于SARS-CoV-2剧毒变体的出现，控制COVID-19大流行的斗争变得具有挑战性。为了深入了解其复制动态，研究人员评估了SARS-CoV-2突发α (A)、β (B)和δ (D)变体在单变体和合并感染中的感染表现。最近发现的广谱抗病毒药物thapsigargin （TG）对这些变异的有效性也进行了研究。在3种病毒中，D型病毒的复制率最高，最容易传播到接触细胞；根据子代病毒RNA的产生，其感染后24 h的复制率（hpi）是变异A的4倍以上，是变异B的9倍以上。在共同感染中，D变体以牺牲自身初始表现为代价，促进了其共同感染伙伴的复制。此外，与AD或AB联合感染产生复制协同作用，其中总后代（RNA）输出大于相应的单变体感染的总和。所有变异对TG抑制高度敏感。在72 hpi时，单次感染前启动剂量的TG有效阻断了所有单变体感染和每种合并感染（AB、AD、BD变体），阻断率大于95%（相对于对照组）。同样地，甘油三酯能有效地抑制活动性感染中的每种变异。综上所述，在当前主要的D变异体可能因与新变异体的共同感染协同作用而进一步复杂化的背景下，越来越多的病毒对TG（一种有前途的以宿主为中心的抗病毒药物）易感，现在包括了当代SARS-CoV-2病毒谱。
The struggle to control the COVID-19 pandemic is made challenging by the emergence of virulent SARS-CoV-2 variants. To gain insight into their replication dynamics, emergent Alpha (A), Beta (B) and Delta (D) SARS-CoV-2 variants were assessed for their infection performance in single variant- and co-infections. The effectiveness of thapsigargin (TG), a recently discovered broad-spectrum antiviral, against these variants was also examined. Of the 3 viruses, the D variant exhibited the highest replication rate and was most able to spread to in-contact cells; its replication rate at 24 h post-infection (hpi) based on progeny viral RNA production was over 4 times that of variant A and 9 times more than the B variant. In co-infections, the D variant boosted the replication of its co-infected partners at the expense of its own initial performance. Furthermore, co-infection with AD or AB combination conferred replication synergy where total progeny (RNA) output was greater than the sum of corresponding single-variant infections. All variants were highly sensitive to TG inhibition. A single pre-infection priming dose of TG effectively blocked all single-variant infections and every combination (AB, AD, BD variants) of co-infection at greater than 95% (relative to controls) at 72 hpi. Likewise, TG was effective in inhibiting each variant in active preexisting infection. In conclusion, against the current backdrop of the dominant D variant that could be further complicated by co-infection synergy with new variants, the growing list of viruses susceptible to TG, a promising host-centric antiviral, now includes a spectrum of contemporary SARS-CoV-2 viruses.
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影响因子：
16.6
作者：
Li B;Deng A;Li K;Hu Y;Li Z;Shi Y;Xiong Q;Liu Z;Guo Q;Zou L;Zhang H;Zhang M;Ouyang F;Su J;Su W;Xu J;Lin H;Sun J;Peng J;Jiang H;Zhou P;Hu T;Luo M;Zhang Y;Zheng H;Xiao J;Liu T;Tan M;Che R;Zeng H;Zheng Z;Huang Y;Yu J;Yi L;Wu J;Chen J;Zhong H;Deng X;Kang M;Pybus OG;Hall M;Lythgoe KA;Li Y;Yuan J;He J;Lu J
通讯作者：
Lu J
DOI：
10.3390/v13020234
发表时间：
2021-02-03
期刊：
Viruses
影响因子：
--
作者：
Al-Beltagi S;Preda CA;Goulding LV;James J;Pu J;Skinner P;Jiang Z;Wang BL;Yang J;Banyard AC;Mellits KH;Gershkovich P;Hayes CJ;Nguyen-Van-Tam J;Brown IH;Liu J;Chang KC
通讯作者：
Chang KC
DOI：
10.3390/v12101093
发表时间：
2020-09-27
期刊：
Viruses
影响因子：
--
作者：
Goulding LV;Yang J;Jiang Z;Zhang H;Lea D;Emes RD;Dottorini T;Pu J;Liu J;Chang KC
通讯作者：
Chang KC
DOI：
10.1056/nejmoa2109072
发表时间：
2021-10-14
期刊：
The New England journal of medicine
影响因子：
--
作者：
Bergwerk M;Gonen T;Lustig Y;Amit S;Lipsitch M;Cohen C;Mandelboim M;Levin EG;Rubin C;Indenbaum V;Tal I;Zavitan M;Zuckerman N;Bar-Chaim A;Kreiss Y;Regev-Yochay G
通讯作者：
Regev-Yochay G
影响因子：
5.2
作者：
Kumar, Naveen;Khandelwal, Nitin;Barua, Sanjay
通讯作者：
Barua, Sanjay