基于新型冠状病毒S蛋白结构及入胞机制的抗体与药物研发

新型冠状病毒肺炎,世界卫生组织命名为"2019冠状病毒病"(corona virus disease 2019,COVID-19),是一种由2019新型冠状病毒(2019-nCov)感染导致的肺炎.目前新冠肺炎在全球广泛流行,且疫情尚未得到全部控制.由于新型冠状病毒表面的刺突蛋白(spike protein,S)介导病...

The SARS-CoV-2 Antibody and Drug Research Based on the Structure of the Spike Protein and the Mechanism of Cell Entry

COVID-19 is a severe acute respiratory syndrome caused by a novel coronavirus, SARS-CoV-2. COVID-19 is now a pandemic, and is not yet fully under control. As the surface spike protein (S) mediates the recognition between the virus and cell membrane and the process of cell entry, it plays an important role in the course of disease transmission. The study on the S protein not only elucidates the structure and function of virus-related proteins and explains their cellular entry mechanism, but also provides valuable information for the prevention, diagnosis and treatment of COVID-19. Concentrated on the S protein of SARS-CoV-2, this review covers four aspects: (1) The structure of the S protein and its binding with angiotensin converting enzyme II (ACE2), the specific receptor of SARS-CoV-2, is introduced in detail. Compared with SARS-CoV, the receptor binding domain (RBD) of the SARS-CoV-2 S protein has a higher affinity with ACE2, while the affinity of the entire S protein is on the contrary. (2) Currently, the cell entry mechanism of SARS-CoV-2 meditated by the S protein is proposed to include endosomal and non-endosomal pathways. With the recognition and binding between the S protein and ACE2 or after cell entry, transmembrane protease serine 2(TMPRSS2), lysosomal cathepsin or the furin enzyme can cleave S protein at S1/S2 cleavage site, facilitating the fusion between the virus and target membrane. (3) For the progress in SARS-CoV-2 S protein antibodies, a collection of significant antibodies are introduced and compared in the fields of the target, source and type. (4) Mechanisms of therapeutic treatments for SARS-CoV-2 varied. Though the antibody and medicine treatments related to the SARS-CoV-2 S protein are of high specificity and great efficacy, the mechanism, safety, applicability and stability of some agents are still unclear and need further assessment. Therefore, to curb the pandemic, researchers in all fields need more cooperation in the development of SARS-CoV-2 antibodies and medicines to face the great challenge.