tetano
Editor, Senior Moderator
J Med Virol
. 2023 Mar 8.
doi: 10.1002/jmv.28641. Online ahead of print.
SARS-CoV-2 Omicron XBB subvariants exhibit enhanced fusogenicity and substantial immune evasion in elderly population, but high sensitivity to pan-coronavirus fusion inhibitors
Shuai Xia[SUP] 1 [/SUP], Fanke Jiao[SUP] 1 [/SUP], Lijue Wang[SUP] 1 [/SUP], Xueying Yu[SUP] 2 [/SUP], Tianyu Lu[SUP] 1 [/SUP], Yan Fu[SUP] 2 [/SUP], Ziqi Huang[SUP] 1 [/SUP], Xicheng Li[SUP] 1 [/SUP], Jinghe Huang[SUP] 1 [/SUP], Qian Wang[SUP] 1 [/SUP], Qiuhong Man[SUP] 2 [/SUP], Lize Xiong[SUP] 2 3 [/SUP], Shibo Jiang[SUP] 1 [/SUP], Lu Lu[SUP] 1 [/SUP]
Affiliations
Abstract
Numerous emerging SARS-CoV-2 Omicron subvariants have shown significant immune evasion capacity and caused a large number of infections, as well as vaccine-breakthrough infections, especially in elderly populations. Recently emerged Omicron XBB was derived from the BA.2 lineage, but bears a distinct mutant profile in its spike (S) protein. In this study, we found that Omicron XBB S protein drove more efficient membrane-fusion kinetics on human lung-derived cells (Calu-3). Considering the high susceptibility of the elderly to the current Omicron pandemic, we performed a comprehensive neutralization assessment of elderly convalescent or vaccinee sera against XBB infection. We found that the sera from elderly convalescent patients experienced with BA.2 infection or breakthrough infection potently inhibited BA.2 infection, but showed significantly reduced efficacy against XBB. Moreover, recently emerged XBB.1.5 subvariant also showed more significant resistance to the convalescent sera of BA.2- or BA.5-infected elderly. On the other hand, we found that the pan-CoV fusion inhibitors EK1 and EK1C4 can potently block either XBB-S- or XBB.1.5-S-mediated fusion process and viral entry. Moreover, EK1 fusion inhibitor showed potent synergism when combined with convalescent sera of BA.2- or BA.5-infected patients against XBB and XBB.1.5 infection, further indicating that EK1-based pan-CoV fusion inhibitors are promising candidates for development as clinical antiviral agents to combat the Omicron XBB subvariants. This article is protected by copyright. All rights reserved.
Keywords: Omicron XBB subvariant; SARS-CoV-2; elderly convalescent; fusion inhibitor; fusogenicity.
. 2023 Mar 8.
doi: 10.1002/jmv.28641. Online ahead of print.
SARS-CoV-2 Omicron XBB subvariants exhibit enhanced fusogenicity and substantial immune evasion in elderly population, but high sensitivity to pan-coronavirus fusion inhibitors
Shuai Xia[SUP] 1 [/SUP], Fanke Jiao[SUP] 1 [/SUP], Lijue Wang[SUP] 1 [/SUP], Xueying Yu[SUP] 2 [/SUP], Tianyu Lu[SUP] 1 [/SUP], Yan Fu[SUP] 2 [/SUP], Ziqi Huang[SUP] 1 [/SUP], Xicheng Li[SUP] 1 [/SUP], Jinghe Huang[SUP] 1 [/SUP], Qian Wang[SUP] 1 [/SUP], Qiuhong Man[SUP] 2 [/SUP], Lize Xiong[SUP] 2 3 [/SUP], Shibo Jiang[SUP] 1 [/SUP], Lu Lu[SUP] 1 [/SUP]
Affiliations
- PMID: 36890632
- DOI: 10.1002/jmv.28641
Abstract
Numerous emerging SARS-CoV-2 Omicron subvariants have shown significant immune evasion capacity and caused a large number of infections, as well as vaccine-breakthrough infections, especially in elderly populations. Recently emerged Omicron XBB was derived from the BA.2 lineage, but bears a distinct mutant profile in its spike (S) protein. In this study, we found that Omicron XBB S protein drove more efficient membrane-fusion kinetics on human lung-derived cells (Calu-3). Considering the high susceptibility of the elderly to the current Omicron pandemic, we performed a comprehensive neutralization assessment of elderly convalescent or vaccinee sera against XBB infection. We found that the sera from elderly convalescent patients experienced with BA.2 infection or breakthrough infection potently inhibited BA.2 infection, but showed significantly reduced efficacy against XBB. Moreover, recently emerged XBB.1.5 subvariant also showed more significant resistance to the convalescent sera of BA.2- or BA.5-infected elderly. On the other hand, we found that the pan-CoV fusion inhibitors EK1 and EK1C4 can potently block either XBB-S- or XBB.1.5-S-mediated fusion process and viral entry. Moreover, EK1 fusion inhibitor showed potent synergism when combined with convalescent sera of BA.2- or BA.5-infected patients against XBB and XBB.1.5 infection, further indicating that EK1-based pan-CoV fusion inhibitors are promising candidates for development as clinical antiviral agents to combat the Omicron XBB subvariants. This article is protected by copyright. All rights reserved.
Keywords: Omicron XBB subvariant; SARS-CoV-2; elderly convalescent; fusion inhibitor; fusogenicity.