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使用靶向前蛋白转化酶(PPC)切割位点的Fv抗体预防严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染。

Preventing SARS-CoV-2 infection using Fv-antibodies targeting the proprotein convertase (PPC) cleavage site.

作者信息

Jung Jaeyong, Sung Jeong Soo, Kwon Soonil, Bae Hyung Eun, Kang Min-Jung, Jose Joachim, Lee Misu, Pyun Jae-Chul

机构信息

Department of Materials Science and Engineering, Yonsei University 50 Yonsei-ro, Seodaemun-gu Seoul 03722 Korea

Korea Institute of Science and Technology (KIST) Seoul 02456 Korea.

出版信息

RSC Med Chem. 2024 Aug 26;15(11):3704-10. doi: 10.1039/d4md00552j.

Abstract

Fv-antibodies targeting the proprotein convertase (PPC) region of the SARS-CoV-2 spike protein (SP) were screened from an Fv-antibody library to inhibit SARS-CoV-2 infection. Two selected Fv-antibodies were expressed as soluble recombinant proteins, and their binding affinities were assessed using a surface plasmon resonance biosensor. The binding regions of these Fv-antibodies corresponded to the cleavage sites of furin (S1/S2) and transmembrane serine protease 2 (TMPRSS2, S2'). The neutralizing activities of the two Fv-antibodies were demonstrated using a cell-based infection assay with pseudo-viruses carrying the SP of four different SARS-CoV-2 variants: wild-type (D614), delta (B.1.617.2), omicron (BA.2), and omicron (BA.4/5).

摘要

从一个Fv抗体文库中筛选靶向严重急性呼吸综合征冠状病毒2(SARS-CoV-2)刺突蛋白(SP)前蛋白转化酶(PPC)区域的Fv抗体,以抑制SARS-CoV-2感染。将两个筛选出的Fv抗体表达为可溶性重组蛋白,并使用表面等离子体共振生物传感器评估它们的结合亲和力。这些Fv抗体的结合区域对应于弗林蛋白酶(S1/S2)和跨膜丝氨酸蛋白酶2(TMPRSS2,S2')的切割位点。使用携带四种不同SARS-CoV-2变体SP的假病毒进行基于细胞的感染试验,证明了这两种Fv抗体的中和活性,这四种变体分别是野生型(D614)、德尔塔(B.1.617.2)、奥密克戎(BA.2)和奥密克戎(BA.4/5)。

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