Jenner Institute, University of Oxfordgrid.4991.5, Oxford, United Kingdom.
Department of Biochemistry, University of Oxfordgrid.4991.5, Oxford, United Kingdom.
mSphere. 2021 Aug 25;6(4):e0064721. doi: 10.1128/mSphere.00647-21. Epub 2021 Aug 11.
Basigin, or CD147, has been reported as a coreceptor used by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to invade host cells. Basigin also has a well-established role in Plasmodium falciparum malaria infection of human erythrocytes, where it is bound by one of the parasite's invasion ligands, reticulocyte binding protein homolog 5 (RH5). Here, we sought to validate the claim that the receptor binding domain (RBD) of SARS-CoV-2 spike glycoprotein can form a complex with basigin, using RH5-basigin as a positive control. Using recombinantly expressed proteins, size exclusion chromatography and surface plasmon resonance, we show that neither RBD nor full-length spike glycoprotein bind to recombinant human basigin (expressed in either Escherichia coli or mammalian cells). Further, polyclonal anti-basigin IgG did not block SARS-CoV-2 infection of Vero E6 cells. Given the immense interest in SARS-CoV-2 therapeutic targets to improve treatment options for those who become seriously ill with coronavirus disease 2019 (COVID-19), we would caution the inclusion of basigin in this list on the basis of its reported direct interaction with SARS-CoV-2 spike glycoprotein. Reducing the mortality and morbidity associated with COVID-19 remains a global health priority. Vaccines have proven highly effective at preventing infection and hospitalization, but efforts must continue to improve treatment options for those who still become seriously ill. Critical to these efforts is the identification of host factors that are essential to viral entry and replication. Basigin, or CD147, was previously identified as a possible therapeutic target based on the observation that it may act as a coreceptor for SARS-CoV-2, binding to the receptor binding domain of the spike protein. Here, we show that there is no direct interaction between the RBD and basigin, casting doubt on its role as a coreceptor and plausibility as a therapeutic target.
Basigin，也称为 CD147，已被报道为严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）入侵宿主细胞的辅助受体。在恶性疟原虫感染人类红细胞的过程中，Basigin 也发挥着重要作用，寄生虫的一种入侵配体——网织红细胞结合蛋白同源物 5（RH5）与 Basigin 结合。在这里，我们试图验证一种说法，即 SARS-CoV-2 刺突糖蛋白的受体结合域（RBD）可以与 Basigin 形成复合物，使用 RH5-Basigin 作为阳性对照。使用重组表达蛋白、排阻层析和表面等离子体共振，我们表明 RBD 或全长刺突糖蛋白均不与重组人 Basigin（在大肠杆菌或哺乳动物细胞中表达）结合。此外，多克隆抗 Basigin IgG 不能阻断 SARS-CoV-2 对 Vero E6 细胞的感染。鉴于人们对 SARS-CoV-2 治疗靶点的极大兴趣，以期改善 2019 年冠状病毒病（COVID-19）患者的治疗选择，我们建议基于 Basigin 与 SARS-CoV-2 刺突糖蛋白的直接相互作用，将其从治疗靶点列表中删除。降低与 COVID-19 相关的死亡率和发病率仍然是全球卫生的重点。疫苗已被证明在预防感染和住院方面非常有效，但必须继续努力改善仍病重患者的治疗选择。这些努力的关键是确定对病毒进入和复制至关重要的宿主因素。Basigin 或 CD147 之前被确定为一种可能的治疗靶点，因为它可能作为 SARS-CoV-2 的辅助受体，与刺突蛋白的受体结合域结合。在这里，我们表明 RBD 与 Basigin 之间没有直接相互作用，这对其作为辅助受体的作用以及作为治疗靶点的合理性提出了质疑。
