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表达针对受体和抗体的SARS-CoV-2刺突变体的单个铁蛋白纳米笼

Single Ferritin Nanocages Expressing SARS-CoV-2 Spike Variants to Receptor and Antibodies.

作者信息

Padariya Monikaben, Kalathiya Umesh

机构信息

International Centre for Cancer Vaccine Science, University of Gdansk, ul. Kładki 24, 80-822 Gdansk, Poland.

出版信息

Vaccines (Basel). 2024 Apr 23;12(5):446. doi: 10.3390/vaccines12050446.

Abstract

SARS-CoV-2 virus variants of concern (VOCs) have rapidly changed their transmissibility and pathogenicity primarily through mutations in the structural proteins. Herein, we present molecular details with dynamics of the ferritin nanocages stitched with synthetic chimeras displaying the Spike receptor binding domains (RBDs). Our findings demonstrated the potential usage of ferritin-based vaccines that may effectively inhibit viral entry by blocking the Spike-ACE2 network and may induce cross-protective antibody responses. Taking the nanocage constructs into consideration, we evaluated the effects of variants on the docked interface of the SARS-CoV-2 Spike RBD with the ACE2 (angiotensin-converting enzyme 2) host cell receptor and neutralizing antibodies (Abs). Investigating the VOCs revealed that most of the mutations reported a possibly reduced structural stability within the Spike RBD domain. Point mutations have moderate or no effect for VVH-72, CR3022, and S309 Abs when bound with the Spike RBD, whereas a significant effect was observed for B38, CB6, and m396 over the surface of the H-ferritin nanocage. In addition to providing useful therapeutic approaches against COVID-19 (coronavirus disease 2019), these structural details can also be used to fight future coronavirus outbreaks.

摘要

严重急性呼吸综合征冠状病毒2(SARS-CoV-2)的关注变异株(VOCs)主要通过结构蛋白的突变迅速改变其传播性和致病性。在此,我们展示了用展示刺突受体结合域(RBDs)的合成嵌合体缝合的铁蛋白纳米笼的分子细节及其动力学。我们的研究结果证明了基于铁蛋白的疫苗的潜在用途,该疫苗可能通过阻断刺突-血管紧张素转换酶2(ACE2)网络有效抑制病毒进入,并可能诱导交叉保护性抗体反应。考虑到纳米笼构建体,我们评估了变异株对SARS-CoV-2刺突RBD与ACE2(血管紧张素转换酶2)宿主细胞受体以及中和抗体(Abs)对接界面的影响。对VOCs的研究表明,报告的大多数突变显示刺突RBD结构域内的结构稳定性可能降低。点突变与刺突RBD结合时,对VVH-72、CR3022和S309抗体的影响中等或无影响,而在H-铁蛋白纳米笼表面,对B38、CB6和m396抗体则观察到显著影响。除了提供针对2019冠状病毒病(COVID-19)的有用治疗方法外,这些结构细节还可用于应对未来的冠状病毒爆发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfb8/11125617/d170015b9be6/vaccines-12-00446-g002.jpg

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