Mechanistic insights into SARS-CoV-2 epidemic via revealing the features of SARS-CoV-2 coding proteins and host responses upon its infection

Abstract

There are seven known coronaviruses that infect humans: four mild coronaviruses, including HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1, only cause mild respiratory diseases, and three severe coronaviruses, including SARS-CoV, MERS-CoV and SARS-CoV-2, can cause severe respiratory diseases even death of infected patients. Both infection and death caused by SARS-CoV-2 are still rapidly increasing worldwide. In this study, we demonstrate that viral coding proteins of SARS-CoV-2 have distinct features and are most, medium and least conserved with SARS-CoV, MERS-CoV, and the rest four mild coronaviruses (HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1), respectively. Moreover, expression of host responsive genes (HRG), HRG-enriched biological processes, and HRG-enriched KEGG pathways upon infection of SARS-CoV-2 show slightly overlapping with SARS-CoV and MERS-CoV but distinctive to the four mild coronaviruses. Interestingly, enrichment of overactivation of neutrophil by HRGs is only and commonly found in infections of severe SARS-CoV-2, SARS-CoV, and MERS-CoV but not in the other four mild coronaviruses, and the related gene networks show different patterns. Clinical data supports that overactivation of neutrophil for severe patients can be one major factor for the similar clinical symptoms observed in SARS-CoV-2 infection compared to infections of the other two severe coronavirus (SARS-CoV, and MERS-CoV). Taken together, our study provides a mechanistic insight into SARS-CoV-2 epidemic via revealing the conserved and distinct features of SARS-CoV-2, raising the critical role of dysregulation of neutrophil for SARS-CoV-2 infection. Supplementary information Supplementary data are available at Bioinformatics online.

Identification of host transcriptome-guided repurposable drugs for SARS-CoV-1 infections and their validation with SARS-CoV-2 infections by using the integrated bioinformatics approaches

“…The 8th key protein ATM plays a central role in responses to various forms of DNA damage, immunodeficiency, virus integration, virus replication and virus infection [ 95 , 96 ]. The 9th key gene CCT2 is a potential drug target against SARS-COV-2 infections [ 93 , 97 , 98 ]. The 10th key gene ETS1 is associated with some potential SARS-COV-2 infections related molecular pathways [ 99 , 100 ].…”

Characteristics of COVID-19 Patients With SARS-CoV-2 Positivity in Feces

“…Elevated peripheral neutrophil counts are associated with cytokine storms and massive neutrophil infiltration of the lungs, resulting in severe lung lesions ( Channappanavar and Perlman, 2017 ). A recent study revealed the distinct characteristics of the viral coding proteins of SARS-CoV-2, and infection with the virus could induce enrichment of host responsive genes related to the overactivation of neutrophils ( Qin et al., 2021 ). This finding suggested the crucial roles of neutrophil dysfunction in COVID-19, which was also found to be a distinct inflammatory feature related to the pathogenesis of SARS and MERS ( Channappanavar and Perlman, 2017 ).…”

Protection against COVID-19 in African population: Immunology, genetics, and malaria clues for therapeutic targets

“…A study of host responsive genes (HRG) for SARS-CoV-2 showed that they are especially enriched in IL-17 signalling, cytokine-cytokine receptor interaction, and NF-kB pathways, among other proceses ( Qin et al, 2020 ). Research has indicated that the NF-kB pathway, which is induced by several mediators, plays a role in cytokine storm ( Mozafari et al, 2020 ).…”

“…The percentage of neutrophils and the absolute value of neutrophils in patients with critical illness and death were always higher than those of non-critically ill patients and surviving patients. This indicates that continued excessive activation of neutrophils plays a crucial role in SARS-CoV-2, leading to severe illness and death ( Qin et al, 2020 ).…”