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

DOI record: { "DOI": "10.3390/cimb48010080", "ISSN": [ "1467-3045" ], "URL": "http://dx.doi.org/10.3390/cimb48010080", "abstract": "<jats:p>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.</jats:p>", "alternative-id": [ "cimb48010080" ], "author": [ { "affiliation": [ { "name": "Department of Biochemistry and Microbiology, University of Fort Hare, Alice Campus, Alice 5700, South Africa" } ], "family": "Sitobo", "given": "Zingisa", "sequence": "first" }, { "ORCID": "https://orcid.org/0000-0003-1815-1272", "affiliation": [ { "name": "Department of Biochemistry, Microbiology and Biotechnology, University of Limpopo, Turfloop Campus, Sovenga 0727, South Africa" } ], "authenticated-orcid": false, "family": "Navhaya", "given": "Liberty T.", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Biochemistry and Microbiology, University of Fort Hare, Alice Campus, Alice 5700, South Africa" } ], "family": "Nqumla", "given": "Ntombekhaya", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Life and Consumer Sciences, College of Agriculture and Environmental Sciences, University of South Africa (UNISA), Florida Campus, Roodepoort 1709, South Africa" } ], "family": "Masenya", "given": "Madipoane", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Life and Consumer Sciences, College of Agriculture and Environmental Sciences, University of South Africa (UNISA), Florida Campus, Roodepoort 1709, South Africa" } ], "family": "Molapo", "given": "Matsheliso", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0002-6939-1199", "affiliation": [ { "name": "Human Genetics Department, Computational Biology Division, Faculty of Health Sciences, University of Cape Town, Barnard Fuller Building, Anzio Rd, Observatory, Cape Town 7935, South Africa" } ], "authenticated-orcid": false, "family": "Mthembu", "given": "Yamkela", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0002-8076-3096", "affiliation": [ { "name": "Department of Life and Consumer Sciences, College of Agriculture and Environmental Sciences, University of South Africa (UNISA), Florida Campus, Roodepoort 1709, South Africa" } ], "authenticated-orcid": false, "family": "Godlo", "given": "Sesethu", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0002-7238-4619", "affiliation": [ { "name": "Department of Life and Consumer Sciences, College of Agriculture and Environmental Sciences, University of South Africa (UNISA), Florida Campus, Roodepoort 1709, South Africa" } ], "authenticated-orcid": false, "family": "Makhoba", "given": "Xolani H.", "sequence": "additional" } ], "container-title": "Current Issues in Molecular Biology", "container-title-short": "CIMB", "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2026, 1, 13 ] ], "date-time": "2026-01-13T18:40:09Z", "timestamp": 1768329609000 }, "deposited": { "date-parts": [ [ 2026, 1, 13 ] ], "date-time": "2026-01-13T18:47:26Z", "timestamp": 1768330046000 }, "funder": [ { "DOI": "10.13039/501100001321", "award": [ "RA22102665148" ], "award-info": [ { "award-number": [ "RA22102665148" ] } ], "doi-asserted-by": "publisher", "id": [ { "asserted-by": "publisher", "id": "10.13039/501100001321", "id-type": "DOI" } ], "name": "National Research Foundation Incentive" } ], "indexed": { "date-parts": [ [ 2026, 1, 14 ] ], "date-time": "2026-01-14T02:19:09Z", "timestamp": 1768357149813, "version": "3.49.0" }, "is-referenced-by-count": 0, "issue": "1", "issued": { "date-parts": [ [ 2026, 1, 13 ] ] }, "journal-issue": { "issue": "1", "published-online": { "date-parts": [ [ 2026, 1 ] ] } }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0/", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2026, 1, 13 ] ], "date-time": "2026-01-13T00:00:00Z", "timestamp": 1768262400000 } } ], "link": [ { "URL": "https://www.mdpi.com/1467-3045/48/1/80/pdf", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "1968", "original-title": [], "page": "80", "prefix": "10.3390", "published": { "date-parts": [ [ 2026, 1, 13 ] ] }, "published-online": { "date-parts": [ [ 2026, 1, 13 ] ] }, "publisher": "MDPI AG", "reference": [ { "DOI": "10.1016/j.cell.2020.07.033", "article-title": "Structural basis for helicase-polymerase coupling in the SARS-CoV-2 replication-transcription complex", "author": "Chen", "doi-asserted-by": "crossref", "first-page": "1560", "journal-title": "Cell", "key": "ref_1", "volume": "182", "year": "2020" }, { "DOI": "10.1001/jamainternmed.2020.0994", "article-title": "Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China", "author": "Wu", "doi-asserted-by": "crossref", "first-page": "934", "journal-title": "JAMA Intern. 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