Coronavirus disease (COVID-19) is an
infectious disease discovered in 2019 and currently in outbreak across the world.
Lung injury with severe
respiratory failure is the leading cause of death in
COVID-19, brought by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2). However, there still lacks efficient treatment for
COVID-19 induced
lung injury and acute
respiratory failure. Inhibition of
Angiotensin-converting enzyme 2 (ACE2) caused by spike
protein of SARS-CoV-2 is the most plausible mechanism of
lung injury in
COVID-19. We propose two candidate drugs,
COL-3 (a chemically modified
tetracycline) and
CGP-60474 (a
cyclin-dependent kinase inhibitor), for treating
lung injuries in
COVID-19, based on their abilities to reverse the gene expression patterns in HCC515 cells treated with ACE2 inhibitor and in human
COVID-19 patient lung tissues. Further bioinformatics analysis shows that twelve significantly enriched pathways (P-value <0.05) overlap between HCC515 cells treated with ACE2 inhibitor and human
COVID-19 patient lung tissues, including signaling pathways known to be associated with
lung injury such as TNF signaling, MAPK signaling and
Chemokine signaling pathways. All these twelve pathways are targeted in
COL-3 treated HCC515 cells, in which genes such as RHOA, RAC2, FAS, CDC42 have reduced expression.
CGP-60474 shares eleven of twelve pathways with
COL-3 with common target genes such as RHOA. It also uniquely targets genes related to
lung injury, such as CALR and MMP14. In summary, this study shows that ACE2 inhibition is likely part of the mechanisms leading to
lung injury in
COVID-19, and that compounds such as
COL-3 and
CGP-60474 have the potential as repurposed drugs for its treatment.