Lung cells transcriptional landscape from COVID-19 patient and a systems biology approach stratified distinct model of...
Abul Islam, Md. Abdullah-Al-Kamran Khan
Received date: 9th June 2020
Full title: Lung cells transcriptional landscape from COVID-19 patient and a systems biology approach stratified distinct model of lung injury in SARS-CoV-2 infection through impaired pulmonary surfactant metabolism which can be mitigated by possible surfactant therapy
Clinical management of COVID-19 is still complicated due to the lack of therapeutic interventions as the molecular mechanisms behind the impaired lung pathobiology of COVID-19 are still largely unknown. In this study, we have analyzed the gene expression pattern in the COVID-19 affected lung biopsy cells and compared it with the effects observed in typical cell lines infected with SARS-CoV-2 and SARS-CoV. Comparison of gene-expression pattern from COVID-19 affected lung tissues and SARS-CoV-2 infected cell-lines is mapped in lung-related process networks to delineate the deregulated pathways involved in the symptomatic impairments observed in COVID-19, which suggest that virus can down-modulate lung functionality related pivotal processes like: hypoxia, lung development, respiratory-processes, cholesterol-biosynthesis and surfactant-metabolism. Impeded surfactant proteins and their regulators SPD, SPC, TTF1 etc. through viral NSP5 and NSP12; dampened thrombosis regulators PLAT, EGR1 by viral ORF8 and NSP12; mitochondrial dysfunction due to aberration of NDUFA10, NDUFAF5, SAMM50 etc. by NSP12; aberration of HIF-1 signaling by SARS-CoV-2 might lead to acute lung injury in COVID-19. Drug enrichment with these process-related deregulated genes advocates probable therapies like: lung surfactants replacement, respiratory stimulants, sargramostim, oseltamivir etc. Our study put forward a distinct mechanism of probable virus induced lung damage apart from cytokine storm.
This is an abstract of a preprint hosted on a preprint server, which is currently undergoing peer review at Scientific Reports. The findings have yet to be thoroughly evaluated, nor has a decision on ultimate publication been made. Therefore, the results reported should not be considered conclusive, and these findings should not be used to inform clinical practice, or public health policy, or be promoted as verified information.