Abstract
In face of the everlasting battle toward COVID-19 and the rapid evolution of SARS-CoV-2, no specific and effective drugs for treating this disease have been reported until today. Angiotensin-converting enzyme 2 (ACE2), a receptor of SARS-CoV-2, mediates the virus infection by binding to spike protein. Although ACE2 is expressed in the lung, kidney, and intestine, its expressing levels are rather low, especially in the lung. Considering the great infectivity of COVID-19, we speculate that SARS-CoV-2 may depend on other routes to facilitate its infection. Here, we first discover an interaction between host cell receptor CD147 and SARS-CoV-2 spike protein. The loss of CD147 or blocking CD147 in Vero E6 and BEAS-2B cell lines by anti-CD147 antibody, Meplazumab, inhibits SARS-CoV-2 amplification. Expression of human CD147 allows virus entry into non-susceptible BHK-21 cells, which can be neutralized by CD147 extracellular fragment. Viral loads are detectable in the lungs of human CD147 (hCD147) mice infected with SARS-CoV-2, but not in those of virus-infected wild type mice. Interestingly, virions are observed in lymphocytes of lung tissue from a COVID-19 patient. Human T cells with a property of ACE2 natural deficiency can be infected with SARS-CoV-2 pseudovirus in a dose-dependent manner, which is specifically inhibited by Meplazumab. Furthermore, CD147 mediates virus entering host cells by endocytosis. Together, our study reveals a novel virus entry route, CD147-spike protein, which provides an important target for developing specific and effective drug against COVID-19.
Highlights
The emergence of SARS-CoV-2 and its rapid spread across the world have triggered a global health emergency
CD147 interacts with SARS-CoV-2 spike protein To investigate whether CD147 involves in SARS-CoV-2 infection, surface plasmon resonance (SPR) and enzyme-linked immunosorbent assay (ELISA) were performed and showed an interaction between CD147 and spike(RBD), with an affinity constant of 1.85 × 10–7 M (Fig. 1a) and half-maximal effective concentration (EC50) of 68.83 μg/mL (Fig. 1b)
Optimized negativestaining electron microscopy (OpNS-EM) showed that the CD147 protein appeared as a folded stick with a junction in the middle, while the spike(RBD) protein appeared near-spherical structures with a diameter of 3 nm
Summary
The emergence of SARS-CoV-2 and its rapid spread across the world have triggered a global health emergency. 2020, there has been an outbreak of COVID-19 around the world, with 44,888,869 confirmed cases and 1,178,475 death cases. Patients with COVID-19 show abnormal findings on chest computed tomography, along with common symptoms that include cough, fever, and fatigue.[1] Middle-aged and elderly patients with underlying comorbidities are susceptible to respiratory failure and may have a poorer prognosis.[2] The pathological features of patients with COVID-19 are very similar to those of patients with SARS and MERS infection.[3] Genetic mutation such as D614G in SARS-CoV-2 spike protein elevated COVID-19 infectivity.[4]
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