Berlin, Apr 08: Scientists have discovered which cells of the lungs and bronchi are targets for novel coronavirus infection, findings that may aid in the development of novel drug candidates to treat COVID-19.
The study, published in The EMBO Journal, revealed that the receptor for the virus is abundantly expressed in the progenitor cells of the respiratory tract which have hair-like projections to sweep mucus and bacteria out of the lungs. Researchers, including those from the Berlin Institute of Health (BIH) in Germany, analysed samples of twelve lung cancer patients obtained from the Heidelberg Lung Biobank in Germany. They also studied cells from the airways of healthy patients, which had been collected in a minimally invasive manner during a bronchoscopy examination performed to rule out lung cancer.
"I was convinced that the data we gathered from these non-coronavirus infected patients would provide important information for understanding the viral infection," said study co-author Roland Eils from BIH.
"We wanted to find out which specific cells the coronavirus attacks," explained Christian Conrad, who also works at the BIH. The scientists said the virus' spike protein attaches to an ACE2 receptor on the cell surface. In addition, they said the virus needs one or more co-factors for it to be able to penetrate cells. Using single-cell sequencing technology, the researchers sequenced the genome of 60,000 cells. "We then analysed a total of nearly 60,000 cells to determine whether they activated the gene for the receptor and potential co-factors, thus in principle allowing them to be infected by the coronavirus," said Soeren Lukassen, one of the lead authors of the study.
"We only found the gene transcripts for ACE2 and for the cofactor TMPRSS2 in very few cells, and only in very small numbers," Lukassen said. The scientists discovered that certain progenitor cells in the bronchi are mainly responsible for producing the coronavirus receptors. These progenitor cells, they said, normally develop into respiratory tract cells lined with hair-like projections called cilia that sweep mucus and bacteria out of the lungs.
"Armed with the knowledge of which cells are attacked, we can now develop targeted therapies," explained co-author Michael Kreuter from the Thorax Clinic at Heidelberg University Hospital in Germany. According to the study, the ACE2 receptor density on the cells increased with age, and was generally higher in men than in women.
"This was only a trend, but it could explain why SARS-CoV-2 has infected more men than women," Eils said. However, the scientists said the sample sizes are too small to make conclusive statements, adding that the study needs to be repeated in larger patient cohorts. "These results show us that the virus acts in a highly selective manner, and that it is dependent on certain human cells in order to spread and replicate," Eils explained.
"The better we understand the interaction between the virus and its host, the better we will be able to develop effective counterstrategies," he added.