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Proline-Proline Dyad in the Fusion Peptide of the Murine β-Coronavirus Spike Protein's S2 Domain Modulates Its Neuroglial Tropism

Safiriyu, AA and Mulchandani, V and Anakkacheri, MN and Pal, D and Das Sarma, J (2023) Proline-Proline Dyad in the Fusion Peptide of the Murine β-Coronavirus Spike Protein's S2 Domain Modulates Its Neuroglial Tropism. In: Viruses, 15 (1).

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Official URL: https://doi.org/10.3390/v15010215


The β-Coronavirus mouse hepatitis virus (MHV-A59)-RSA59 has a patent stretch of fusion peptide (FP) containing two consecutive central prolines (PP) in the S2 domain of the Spike protein. Our previous studies compared the PP-containing fusogenic-demyelinating strain RSA59(PP) to its one proline-deleted mutant strain RSA59(P) and one proline-containing non-fusogenic non-demyelinating parental strain RSMHV2(P) to its one proline inserted mutant strain RSMHV2(PP). These studies highlighted the crucial role of PP in fusogenicity, hepato-neuropathogenesis, and demyelination. Computational studies combined with biophysical data indicate that PP at the center of the FP provides local rigidity while imparting global fluctuation to the Spike protein that enhances the fusogenic properties of RSA59(PP) and RSMHV2(PP). To elaborate on the understanding of the role of PP in the FP of MHV, the differential neuroglial tropism of the PP and P mutant strains was investigated. Comparative studies demonstrated that PP significantly enhances the viral tropism for neurons, microglia, and oligodendrocytes. PP, however, is not essential for viral tropism for either astroglial or oligodendroglial precursors or the infection of meningeal fibroblasts in the blood-brain and blood-CSF barriers. PP in the fusion domain is critical for promoting gliopathy, making it a potential region for designing antivirals for neuro-COVID therapy.

Item Type: Journal Article
Publication: Viruses
Publisher: NLM (Medline)
Additional Information: The copyright for this article belongs to the Authors.
Keywords: coronavirus spike glycoprotein; peptide; proline; spike protein, SARS-CoV-2; virus envelope protein, animal; genetics; metabolism; mouse; Murine hepatitis virus; physiology; tropism, Animals; COVID-19; Mice; Murine hepatitis virus; Peptides; Proline; Spike Glycoprotein, Coronavirus; Tropism; Viral Envelope Proteins
Department/Centre: Division of Interdisciplinary Sciences > Computational and Data Sciences
Date Deposited: 16 Feb 2023 04:58
Last Modified: 16 Feb 2023 04:58
URI: https://eprints.iisc.ac.in/id/eprint/80297

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