Perspectives on the development of neutralizing antibodies against SARS-CoV-2.
Perspectives on the development of neutralizing antibodies against SARS-CoV-2.
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DOI：
10.1093/abt/tbaa009
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发表时间：
2020-04-01
影响因子：
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通讯作者：
Ho, Mitchell
中科院分区：
文献类型：
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作者：
Ho, Mitchell
SARS-CoV-2通过与血管紧张素转换酶2（ACE 2）结合的刺突蛋白（S）进入人体细胞。因此，S蛋白的受体结合结构域（RBD）是中和抗体的主要靶标。选择针对SARS-CoV-2和SARS-CoV的广泛中和抗体是有吸引力的，不仅可能用于治疗COVID-19，而且可能用于治疗未来的SARS相关CoV感染。广泛中和抗体，如47 D11、S309和VHH-72，已被报道靶向S1亚基的RBD中的保守区域。病毒膜融合所需的S2亚基可能是另一个靶点。由于它们的小尺寸和高稳定性，单结构域抗体可能具有通过吸入器施用的能力，使得它们成为呼吸道感染的潜在有吸引力的治疗剂。将两种（或更多种）抗体结合起来的鸡尾酒策略可能是最有效的，这些抗体可以识别与人类细胞相互作用的病毒表面的不同部分。
SARS-CoV-2 gains entry to human cells through its spike (S) protein binding to angiotensin-converting enzyme 2 (ACE2). Therefore, the receptor binding domain (RBD) of the S protein is the primary target for neutralizing antibodies. Selection of broad-neutralizing antibodies against SARS-CoV-2 and SARS-CoV is attractive and might be useful for treating not only COVID-19 but also future SARS-related CoV infections. Broad-neutralizing antibodies, such as 47D11, S309, and VHH-72, have been reported to target a conserved region in the RBD of the S1 subunit. The S2 subunit required for viral membrane fusion might be another target. Due to their small size and high stability, single-domain antibodies might have the ability to be administered by an inhaler making them potentially attractive therapeutics for respiratory infections. A cocktail strategy combining two (or more) antibodies that recognize different parts of the viral surface that interact with human cells might be the most effective.