Structural basis for accommodation of emerging B.1.351 and B.1.1.7 variants by two potent SARS-CoV-2 neutralizing antibodies

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新冠病毒中和单克隆抗体及纳米抗体研究进展北大核心CSCD

由严重急性呼吸系统综合征冠状病毒2型(severe acute respiratory syndrome coronavirus-2,SARS-CoV-2)引起的疾病被命名为新型冠状病毒肺炎(coronavirus disease 2019,COVID-19),是一种具有强传染性、高易感性、长潜伏期的传染病。病毒刺突蛋白受体结合结构域(receptor binding domain,RBD)和细胞血管紧张素转换酶2(angiotensin-converting enzyme 2,ACE2)之间的相互作用使得SARS-CoV-2顺利进入细胞。本文对SARS-CoV-2与ACE2的相关作用机制进行了简单概述,对目前针对SARS-CoV-2中和单克隆抗体、纳米抗体的最新研究进展进行了总结,探讨了新冠肺炎的发展过程和抗体药物的研究方向,以期为包括新冠肺炎在内的新发、突发传染病中和抗体药物的研发提供参考。     

SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies

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Potent SARS-CoV-2 neutralizing antibodies directed against spike N-terminal domain target a single supersite

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新型冠状病毒及泛β冠状病毒广谱中和单抗的研究进展

新型冠状病毒的全球大流行,给人类的生命健康和社会秩序带来了巨大的危害。疫苗、小分子药物及各类抗体药物的研发在遏制新型冠状病毒感染传播、降低重症率和死亡风险上发挥了积极的作用。然而,由于新冠病毒庞大的感染基数及自身易突变的特征,当前已经演化出多种能逃逸疫苗及中和抗体的变异株,显著削弱了抗体的保护效果。研发新型冠状病毒广谱甚至泛β冠状病毒广谱的中和抗体对于未来新冠变异株及其他高致病性β冠状病毒的防治具有重要意义。本文从新型冠状病毒中和抗体的筛选制备策略、作用机制、中和效果及广谱性等方面进行了系统综述,并对当前面临的挑战和未来的发展方向进行了讨论和展望,以期为后续相关研究提供参考。     

Neutralizing immunity in vaccine breakthrough infections from the SARS-CoV-2 Omicron and Delta variants

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Virological and immunological features of SARS-CoV-2-infected children who develop neutralizing antibodies

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抗新型冠状病毒中和抗体药物临床研究进展北大核心CSCD

自1998年预防呼吸合胞病毒的帕利珠单抗药物上市以来,多种靶向病毒的治疗性抗体药物已成功用于感染性疾病的临床治疗。新型冠状病毒肺炎疫情暴发后,多种中和抗体药物快速进入临床研究阶段,展现出积极的治疗及预防效果,并以紧急使用授权的方式用于疫情防控。本文对抗新型冠状病毒中和抗体药物的临床进展和主要临床试验结果进行总结,以期为包括新型冠状病毒肺炎在内的新发、突发传染病中和抗体药物研发提供参考。     

B.1.617.2 (Delta) Variant of SARS-CoV-2: features,transmission and potential strategies

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic. With the continuous evolution of the viral genome, SARS-CoV-2 has evolved many variants. B.1.617.2, also called Delta, is one of the most concerned variants. The Delta variant was first reported in India at the end of 2020 but has spread globally, by now, to 135 countries and is not stand still. Delta shared some mutations with other variants, and owned its special mutations on spike proteins, which may be responsible for its strong transmission and increasing virulence. Under these circumstances, a systematic summary of Delta is necessary. This review will focus on the Delta variant. We will describe all the characteristics of Delta (including biological features and clinical characteristics), analyze potential reasons for its strong transmission, and provide potential protective ways for combating Delta.     

Humoral Immunity against SARS-CoV-2 and the Impact on COVID-19 Pathogenesis

It has been more than a year since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first emerged. Many studies have provided insights into the various aspects of the immune response in coronavirus disease 2019 (COVID-19). Especially for antibody treatment and vaccine development, humoral immunity to SARS-CoV-2 has been studied extensively, though there is still much that is unknown and controversial. Here, we introduce key discoveries on the humoral immune responses in COVID-19, including the immune dynamics of antibody responses and correlations with disease severity, neutralizing antibodies and their cross-reactivity, how long the antibody and memory B-cell responses last, aberrant autoreactive antibodies generated in COVID-19 patients, and the efficacy of currently available therapeutic antibodies and vaccines against circulating SARS-CoV-2 variants, and highlight gaps in the current knowledge.     

Structural insight into SARS-CoV-2 neutralizing antibodies and modulation of syncytia

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SARS-CoV-2 variant B.1.1.7 is susceptible to neutralizing antibodies elicited by ancestral spike vaccines

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In vitro and in vivo functions of SARS-CoV-2 infection-enhancing and neutralizing antibodies

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The antibody response to SARS-CoV-2 Beta underscores the antigenic distance to other variants

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Robust SARS-CoV-2 infection in nasal turbinates after treatment with systemic neutralizing antibodies

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Discovery of ultrapotent broadly neutralizing antibodies from SARS-CoV-2 elite neutralizers

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Cross-reactivity of SARS-CoV structural protein antibodies against SARS-CoV-2

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The monoclonal antibody combination REGEN-COV protects against SARS-CoV-2 mutational escape in preclinical and human studies

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Increased pathogenicity and aerosol transmission for one SARS-CoV-2 B.1.617.2 Delta variant over the wild-type strain in hamsters

During the two-year pandemic of coronavirus disease 2019 (COVID-19), its causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been evolving. SARS-CoV-2 Delta, a variant of concern, has become the dominant circulating strain worldwide within just a few months. Here, we performed a comprehensive analysis of a new B.1.617.2 Delta strain (Delta630) compared with the early WIV04 strain (WIV04) in vitro and in vivo, in terms of replication, infectivity, pathogenicity, and transmission in hamsters. When inoculated intranasally, Delta630 led to more pronounced weight loss and more severe disease in hamsters. Moreover, 40% mortality occurred about one week after infection with 10⁴ PFU of Delta630, whereas no deaths occurred even after infection with 10⁵ PFU of WIV04 or other strains belonging to the Delta variant. Moreover, Delta630 outgrew over WIV04 in the competitive aerosol transmission experiment. Taken together, the Delta630 strain showed increased replication ability, pathogenicity, and transmissibility over WIV04 in hamsters. To our knowledge, this is the first SARS-CoV-2 strain that causes death in a hamster model, which could be an asset for the efficacy evaluation of vaccines and antivirals against infections of SARS-CoV-2 Delta strains. The underlying molecular mechanisms of increased virulence and transmission await further analysis.