SARS-CoV-2 invades host cells via a novel route: CD147-spike protein

Authors: Wang, K. et al. Link to paper: https://doi.org/10.1101/2020.03.14.988345

Journal/ Pre-Print: bioRxiv

Key Words: CD147, Spike protein, SARS-CoV-2, Invasive route

RESEARCH HIGHLIGHTS

1. Report a novel route of SARS-CoV-2 host cell invasion through spike protein interaction with CD147.

2. Mepolizumab (anti-CD147 antibody) significantly inhibited the virus from invading host cells by inhibiting the CD147-SP interaction.

3. Novel route presents a new potential target for developing anti-viral drugs.

SUMMARY 

SARS-CoV-2 invades host cells via interaction of its spike protein (SP) with membrane receptor ACE2. Other receptors for SP binding on the host cell membrane are unknown. Wang et al. report a novel route of SARS-CoV-2 invasion through SP interaction with transmembrane glycoprotein, CD147. In vitro anti-viral tests indicate that Meplazumab, an anti-CD147 humanized antibody, inhibited SARS-CoV-2 from invading host cells. The interaction between CD147 and SP was validated by SPR, co-immunoprecipitation and ELISA. Immuno-electron microscopy was used to observe CD147 and SP in SARS-CoV-2 infected cells. This novel invasion route for SARS-CoV-2 provides a new target for anti-viral drug development.

Impact for SARS-CoV2/COVID19 research efforts

Understanding the virology and/or cell biology of SARS-CoV2/COVID19

Treating SARS-CoV2/COVID19 positive individuals

STUDY TYPE

· In vitro study

STRENGTHS AND LIMITATIONS OF THE PAPER

Novelty:

Reports a novel receptor for SARS-CoV-2 spike protein, CD147, and that CD147-SP interaction facilitates SARS-CoV-2 invasion. This is a previously unknown invasion route.

Standing in the field:

Significant understanding that SARS-CoV-2 spike protein interacts with membrane protein receptor ACE2, which contributes to SARS-CoV-2 invasion of host cells. However, other receptors for the spike protein are unknown. CD147 is also a membrane receptor and has been previously shown to play a functional role in SARS-CoV host cell invasion.

Appropriate statistics:

No statistical analysis as only single repeats of each experiment.

Viral model used:

SARS-CoV-2 (100TCID50)

Translatability:

Do show that previously known drug, Meplazumab, effectively inhibits SARS-CoV-2 replication but do not further investigate its use as an antiviral drug for COVID-19 so it is not immediately translatable.

Main limitations:

· No repeats of the experiments mentioned, the results appear to be from one repeat of each experiment. Therefore, there is no statistical analysis.

· Experiments are lacking control conditions eg. Inhibition of SARS-CoV-2 replication experiment without addition of antibody or with an antibody not specific to CD147, control showing antibody specificity to CD147 co-IP loading controls are missing,etc.

· Methods are missing some detailed information such as the primers used for qPCR analysis.

· Lacking essential further experiments to validate their conclusions for example, the effect of disrupting this interaction by mutating SARS-CoV-2 and thereby inhibit host cell invasion.