In silico and in vitro studies reveal complement system drives coagulation cascade in SARS-CoV-2 pathogenesis.

Computational and Structural Biotechnology Journal
Ritudhwaj TiwariDebasis Nayak

Abstract

The emergence and continued spread of SARS-CoV-2 have resulted in a public health emergency across the globe. The lack of knowledge on the precise mechanism of viral pathogenesis is impeding medical intervention. In this study, we have taken both in silico and in vitro experimental approaches to unravel the mechanism of viral pathogenesis associated with complement and coagulation pathways. Based on the structural similarities of viral and host proteins, we initially generated a protein-protein interactome profile. Further computational analysis combined with Gene Ontology (GO) analysis and KEGG pathway analysis predicted key annotated pathways associated with viral pathogenesis. These include MAPK signaling, complement, and coagulation cascades, endocytosis, PD-L1 expression, PD-1 checkpoint pathway in cancer and C-type lectin receptor signaling pathways. Degree centrality analysis pinned down to MAPK1, MAPK3, AKT1, and SRC are crucial drivers of signaling pathways and often overlap with the associated pathways. Most strikingly, the complement and coagulation cascade and platelet activation pathways are interconnected, presumably directing thrombotic activity observed in severe or critical cases of COVID-19. This is complement...Continue Reading

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Citations

Jan 29, 2021·Journal of Biomolecular Structure & Dynamics·Ritudhwaj TiwariDebasis Nayak
Apr 8, 2021·Infectious Diseases and Therapy·Alanna C McEneny-KingStephan R Ortiz
May 13, 2021·Indian Journal of Pharmacology·Hardeep KaurBikash Medhi

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Methods Mentioned

BETA
in silico methods
Profiler
interaction predictions
RNA-seq
ubiquitination

Software Mentioned

STRING
R package LIMMA
Dali
CytoNCA
LIMMA
Profiler
DaliLite
Reactome
Cytoscape
: Profiler

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