Regulatory Cross Talk Between SARS-CoV-2 Receptor Binding and Replication Machinery in the Human Host

被引:20
作者
Ahmed, Shiek S. S. J. [1 ]
Paramasivam, Prabu [2 ,3 ]
Raj, Kamal [3 ]
Kumar, Vishal [4 ]
Murugesan, Ram [1 ]
Ramakrishnan, V [5 ]
机构
[1] Chettinad Acad Res & Educ, Fac Allied Hlth Sci, Drug Discovery & Multiom Lab, Kelambakkam, India
[2] Univ New Mexico, Sch Med, Dept Neurol, Hlth Sci Ctr, Albuquerque, NM 87131 USA
[3] Madras Diabet Res Fdn, Chennai, Tamil Nadu, India
[4] Ctr AIDS & Res Educ, YRG CARE, Dept Immunol, Chennai, Tamil Nadu, India
[5] Chettinad Acad Res & Educ, Fac Allied Hlth Sci, Genet, Kelambakkam, India
关键词
SARS-CoV-2; Covid-19; transcriptome; systems biology; host mechanism; miRNA targets; COVID-19;
D O I
10.3389/fphys.2020.00802
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
We dissect the mechanism of SARS-CoV-2 in human lung host from the initial phase of receptor binding to viral replication machinery. Two independent lung protein interactome were constructed to reveal the signaling process on receptor activation and host protein hijacking machinery in the pathogenesis of virus. Further, we test the functional role of the hubs derived from the interactome. Most hubs proteins were differentially regulated on SARS-CoV-2 infection. Also, the proteins in viral replication hubs were related with cardiovascular disease, diabetes and hypertension confirming the vulnerability and severity of infection in the risk individual. Additionally, the hub proteins were closely linked with other viral infection, including MERS and HCoVs which suggest similar infection pattern in SARS-CoV-2. We identified five hubs that interconnect both networks that show the preparation of optimal environment in the host for viral replication process upon receptor attachment. Interestingly, we propose that seven potential miRNAs, targeting the intermediate phase that connects receptor and viral replication process a better choice as a drug for SARS-CoV-2.
引用
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页数:13
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