SARS-CoV-2 Helicase (NSP13) Interacts with Mammalian Polyamine and HSP Partners in Promoting Viral Replication

TL;DR

This study explores how the SARS-CoV-2 helicase interacts with host proteins to aid viral replication.

Contribution

The study identifies new interaction hotspots and behaviors of NSP13 complexes with host proteins.

Findings

HSP70-NSP13 complexes adopt compact conformations.

HSP90-NSP13 ensembles show conformational heterogeneity but favorable stability estimates.

ODC-NSP13 interfaces are well packed with key residues Lys22 and Asn51 as hotspots.

Abstract

We present a computational study that precedes the potential interactions between SARS-CoV-2 helicase (NSP13) and selected host proteins implicated in chaperone-assisted folding and polyamine metabolism. Using structure-based modelling and protein–protein docking (BioLuminate v4.6), followed by all-atom molecular dynamics (MD) simulations (GROMACS v2018.6), and comparative MM-GBSA scoring (HawkDock v2), we evaluated the stability and interface properties of NSP13 complexes with cytosolic heat shock proteins; heat shock protein 40 (HSP40), heat shock protein 70 (HSP70), heat shock protein 90 (HSP90) and the polyamine biosynthesis enzyme ornithine decarboxylase (ODC). Docking, MD, and interface analyses indicate distinct complex behaviours: HSP70-NSP13 complexes sampled compact conformations, HSP90-NSP13 ensembles displayed greater conformational heterogeneity but more favourable comparative MM-GBSA estimates, and ODC-NSP13 interfaces were comparatively well packed. Per-residue contact mapping identified a small set of recurrent NSP13 residues, Lys22 and Asn51, as putative interaction hotspots. The reported findings herein generate testable hypotheses about NSP13 recruitment of host chaperones and modulation of polyamine metabolism that may inform downstream experimental studies.

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