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

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 pathogenes...

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Main Authors: Shiek S. S. J. Ahmed, Prabu Paramasivam, Kamal Raj, Vishal Kumar, Ram Murugesan, V. Ramakrishnan
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-06-01
Series:Frontiers in Physiology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fphys.2020.00802/full
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author Shiek S. S. J. Ahmed
Prabu Paramasivam
Prabu Paramasivam
Kamal Raj
Vishal Kumar
Ram Murugesan
V. Ramakrishnan
author_facet Shiek S. S. J. Ahmed
Prabu Paramasivam
Prabu Paramasivam
Kamal Raj
Vishal Kumar
Ram Murugesan
V. Ramakrishnan
author_sort Shiek S. S. J. Ahmed
collection DOAJ
description 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.
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spelling doaj.art-694cf93c94d6474ab8c9e1080622f1122022-12-21T19:20:45ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2020-06-011110.3389/fphys.2020.00802560663Regulatory Cross Talk Between SARS-CoV-2 Receptor Binding and Replication Machinery in the Human HostShiek S. S. J. Ahmed0Prabu Paramasivam1Prabu Paramasivam2Kamal Raj3Vishal Kumar4Ram Murugesan5V. Ramakrishnan6Drug Discovery and Multi-Omics Laboratory, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education, Kelambakkam, IndiaDepartment of Neurology, School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, United StatesMadras Diabetes Research Foundation, Chennai, IndiaMadras Diabetes Research Foundation, Chennai, IndiaDepartment of Immunology, YRG CARE, Centre for AIDS and Research Education, Chennai, IndiaDrug Discovery and Multi-Omics Laboratory, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education, Kelambakkam, IndiaGenetics, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education, Kelambakkam, IndiaWe 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.https://www.frontiersin.org/article/10.3389/fphys.2020.00802/fullSARS-CoV-2Covid-19transcriptomesystems biologyhost mechanismmiRNA targets
spellingShingle Shiek S. S. J. Ahmed
Prabu Paramasivam
Prabu Paramasivam
Kamal Raj
Vishal Kumar
Ram Murugesan
V. Ramakrishnan
Regulatory Cross Talk Between SARS-CoV-2 Receptor Binding and Replication Machinery in the Human Host
Frontiers in Physiology
SARS-CoV-2
Covid-19
transcriptome
systems biology
host mechanism
miRNA targets
title Regulatory Cross Talk Between SARS-CoV-2 Receptor Binding and Replication Machinery in the Human Host
title_full Regulatory Cross Talk Between SARS-CoV-2 Receptor Binding and Replication Machinery in the Human Host
title_fullStr Regulatory Cross Talk Between SARS-CoV-2 Receptor Binding and Replication Machinery in the Human Host
title_full_unstemmed Regulatory Cross Talk Between SARS-CoV-2 Receptor Binding and Replication Machinery in the Human Host
title_short Regulatory Cross Talk Between SARS-CoV-2 Receptor Binding and Replication Machinery in the Human Host
title_sort regulatory cross talk between sars cov 2 receptor binding and replication machinery in the human host
topic SARS-CoV-2
Covid-19
transcriptome
systems biology
host mechanism
miRNA targets
url https://www.frontiersin.org/article/10.3389/fphys.2020.00802/full
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