Neurological pathophysiology of SARS-CoV-2 and pandemic potential RNA viruses: a comparative analysis.
Neurological pathophysiology of SARS-CoV-2 and pandemic potential RNA viruses: a comparative analysis.
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DOI：
10.1002/1873-3468.14227
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发表时间：
2021-12
期刊：
影响因子：
3.5
通讯作者：
Arumugaswami V
中科院分区：
文献类型：
--
作者：
Chakravarty N;Senthilnathan T;Paiola S;Gyani P;Castillo Cario S;Urena E;Jeysankar A;Jeysankar P;Ignatius Irudayam J;Natesan Subramanian S;Lavretsky H;Joshi S;Garcia G Jr;Ramaiah A;Arumugaswami V
SARS-CoV-2已经感染了数亿人，造成400多万人死亡，导致了近期历史上最严重的全球大流行之一。与COVID-19相关的神经系统症状包括嗅觉缺失、老年痴呆、头痛、精神错乱、谵妄和中风。这可能是由于病毒通过血脑屏障（BBB）以不明确的机制进入中枢神经系统（CNS）。本文总结了SARS-CoV-2和其他嗜神经RNA病毒（包括寨卡病毒和尼帕病毒）穿过血脑屏障进入中枢神经系统的能力，强调了磁共振成像（MRI）在评估COVID-19患者大脑结构变化的存在和严重程度方面的作用。我们对SARS-CoV-2变体B.1.1.7 （P681H）和B.1.617.2 （P681R）的关键突变有了新的认识，这些突变可能影响神经素-1 （NRP1）的结合和中枢神经系统的侵袭。我们假设SARS-CoV-2可能感染能够穿过血脑屏障的外周细胞和脑内皮细胞，从而穿过血脑屏障并扩散到大脑。COVID-19患者可以通过MRI方式随访，以更好地了解COVID-19对大脑的长期影响。冠状病毒和潜在的大流行RNA病毒可以通过各种机制到达大脑，从而诱发神经系统症状。对SARS-CoV-2神经元进入共受体NRP1与Spike蛋白相互作用的结构分析揭示了现有相关变异中的关键突变，这些突变可能影响NRP1的结合，以及SARS-CoV-2向大脑的传播。利用核磁共振成像技术对追踪病毒介导的大脑结构变化至关重要。
SARS-CoV-2 has infected hundreds of millions of people with over four million dead, resulting in one of the worst global pandemics in recent history. Neurological symptoms associated with COVID-19 include anosmia, ageusia, headaches, confusion, delirium and strokes. These may manifest due to viral entry into the central nervous system (CNS) through the blood-brain barrier (BBB) by means of ill-defined mechanisms. Here we summarize the abilities of SARS-CoV-2 and other neurotropic RNA viruses, including Zika virus and Nipah virus, to cross the BBB into the CNS, highlight the role of magnetic resonance imaging (MRI) in assessing presence and severity of brain structural changes in COVID-19 patients. We present new insight into key mutations in SARS-CoV-2 variants B.1.1.7 (P681H) and B.1.617.2 (P681R), which may impact on neuropilin-1 (NRP1) binding and CNS invasion. We postulate that SARS-CoV-2 may infect both peripheral cells capable of crossing the BBB and brain endothelial cells to traverse the BBB and spread into the brain. COVID-19 patients can be followed up with MRI modalities to better understand the long-term effects of COVID-19 on the brain. Coronaviruses and pandemic-potential RNA viruses can reach the brain using various mechanisms and thereby induce neurological symptoms. Structural analysis of SARS-CoV-2 neuronal entry co-receptor NRP1 interacting with the Spike protein revealed key mutations among existing variants of concern, which could affect NRP1 binding, and SARS-CoV-2 spread into the brain. Utilization of MRI modalities would be crucial for tracking viral-mediated structural changes to the brain.
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