Two Consecutive Prolines in the Fusion Peptide of Murine β-Coronavirus Spike Protein Predominantly Determine Fusogenicity and May Be Essential but Not Sufficient to Cause Demyelination

Combined in silico, in vitro, and in vivo comparative studies between isogenic-recombinant Mouse-Hepatitis-Virus-RSA59 and its proline deletion mutant, revealed a remarkable contribution of centrally located two consecutive prolines (PP) from Spike protein fusion peptide (FP) in enhancing virus fuso...

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Main Authors: Behera, A. (Author), Das Sarma, J. (Author), Kishore, A. (Author), Maity, D. (Author), Mulchandani, V. (Author), Pal, D. (Author), Safiriyu, A.A (Author), Singh, M. (Author), Sinha, B. (Author)
Format: Article
Language:English
Published: NLM (Medline) 2022
Subjects:
Online Access:View Fulltext in Publisher
LEADER 03016nam a2200529Ia 4500
001 10.3390-v14040834
008 220510s2022 CNT 000 0 und d
020 |a 19994915 (ISSN) 
245 1 0 |a Two Consecutive Prolines in the Fusion Peptide of Murine β-Coronavirus Spike Protein Predominantly Determine Fusogenicity and May Be Essential but Not Sufficient to Cause Demyelination 
260 0 |b NLM (Medline)  |c 2022 
856 |z View Fulltext in Publisher  |u https://doi.org/10.3390/v14040834 
520 3 |a Combined in silico, in vitro, and in vivo comparative studies between isogenic-recombinant Mouse-Hepatitis-Virus-RSA59 and its proline deletion mutant, revealed a remarkable contribution of centrally located two consecutive prolines (PP) from Spike protein fusion peptide (FP) in enhancing virus fusogenic and hepato-neuropathogenic potential. To deepen our understanding of the underlying factors, we extend our studies to a non-fusogenic parental virus strain RSMHV2 (P) with a single proline in the FP and its proline inserted mutant, RSMHV2 (PP). Comparative in vitro and in vivo studies between virus strains RSA59(PP), RSMHV2 (P), and RSMHV2 (PP) in the FP demonstrate that the insertion of one proline significantly resulted in enhancing the virus fusogenicity, spread, and consecutive neuropathogenesis. Computational studies suggest that the central PP in Spike FP induces a locally ordered, compact, and rigid structure of the Spike protein in RSMHV2 (PP) compared to RSMHV2 (P), but globally the Spike S2-domain is akin to the parental strain RSA59(PP), the latter being the most flexible showing two potential wells in the energy landscape as observed from the molecular dynamics studies. The critical location of two central prolines of the FP is essential for fusogenicity and pathogenesis making it a potential site for designing antiviral. 
650 0 4 |a animal 
650 0 4 |a Animals 
650 0 4 |a cell-to-cell fusion (fusogenicity) 
650 0 4 |a coronavirus spike glycoprotein 
650 0 4 |a demyelinating disease 
650 0 4 |a Demyelinating Diseases 
650 0 4 |a demyelination 
650 0 4 |a fusion peptide/FP 
650 0 4 |a genetics 
650 0 4 |a hepatitis 
650 0 4 |a metabolism 
650 0 4 |a Mice 
650 0 4 |a mouse 
650 0 4 |a mouse hepatitis virus-2/MHV2 spike protein 
650 0 4 |a mouse hepatitis virus-A59/MHV-A59 
650 0 4 |a neuropathogenesis 
650 0 4 |a peptide 
650 0 4 |a Peptides 
650 0 4 |a proline 
650 0 4 |a Proline 
650 0 4 |a Spike Glycoprotein, Coronavirus 
650 0 4 |a structural rigidity 
650 0 4 |a Viral Envelope Proteins 
650 0 4 |a virus envelope protein 
650 0 4 |a β-Coronavirus 
700 1 |a Behera, A.  |e author 
700 1 |a Das Sarma, J.  |e author 
700 1 |a Kishore, A.  |e author 
700 1 |a Maity, D.  |e author 
700 1 |a Mulchandani, V.  |e author 
700 1 |a Pal, D.  |e author 
700 1 |a Safiriyu, A.A.  |e author 
700 1 |a Singh, M.  |e author 
700 1 |a Sinha, B.  |e author 
773 |t Viruses