Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses

• Published in: Nature microbiology Vol. 5; no. 4; pp. 562 - 569
• Main Authors: Letko, Michael, Marzi, Andrea, Munster, Vincent
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2020; Nature Publishing Group
• Subjects: 13/106; 14/63; 38/109; 38/22; 38/23; 38/44; 38/70; 38/77; 42; 42/109; 631/326/596/2078; 631/326/596/2557; 631/326/596/2563; ACE2; Angiotensin-Converting Enzyme 2; Animals; Betacoronavirus - chemistry; Betacoronavirus - classification; Betacoronavirus - physiology; Biomedical and Life Sciences; CD13 Antigens - metabolism; Cell Line; Coronaviridae; Coronavirus Infections - metabolism; Coronavirus Infections - virology; Coronaviruses; COVID-19; Dipeptidyl Peptidase 4 - metabolism; Humans; Infectious Diseases; Life Sciences; Medical Microbiology; Microbiology; Mutation; Outbreaks; Pandemics; Parasitology; Peptidyl-Dipeptidase A - chemistry; Peptidyl-Dipeptidase A - genetics; Peptidyl-Dipeptidase A - metabolism; Pneumonia, Viral - metabolism; Pneumonia, Viral - virology; Protein Domains; Proteinase; Receptors, Coronavirus; Receptors, Virus - chemistry; Receptors, Virus - genetics; Receptors, Virus - metabolism; Recombinant Fusion Proteins - metabolism; SARS Virus - chemistry; SARS Virus - physiology; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Species; Spike Glycoprotein, Coronavirus - chemistry; Spike Glycoprotein, Coronavirus - genetics; Spike Glycoprotein, Coronavirus - metabolism; Trypsin - metabolism; Virology; Virus Internalization; Viruses
• ISSN: 2058-5276; 2058-5276
• DOI: 10.1038/s41564-020-0688-y

Over the past 20 years, several coronaviruses have crossed the species barrier into humans, causing outbreaks of severe, and often fatal, respiratory illness. Since SARS-CoV was first identified in animal markets, global viromics projects have discovered thousands of coronavirus sequences in diverse animals and geographic regions. Unfortunately, there are few tools available to functionally test these viruses for their ability to infect humans, which has severely hampered efforts to predict the next zoonotic viral outbreak. Here, we developed an approach to rapidly screen lineage B betacoronaviruses, such as SARS-CoV and the recent SARS-CoV-2, for receptor usage and their ability to infect cell types from different species. We show that host protease processing during viral entry is a significant barrier for several lineage B viruses and that bypassing this barrier allows several lineage B viruses to enter human cells through an unknown receptor. We also demonstrate how different lineage B viruses can recombine to gain entry into human cells, and confirm that human ACE2 is the receptor for the recently emerging SARS-CoV-2. This study describes the development of an approach to rapidly screen lineage B betacoronaviruses, such as SARS-CoV and the recently emerged SARS-CoV-2, for receptor usage and their ability to infect cell types from different species. Using it, they confirm human ACE2 as the receptor for SARs-CoV-2 and show that host protease processing during viral entry is a significant barrier for viral entry.