A Conservative Replacement in the Transmembrane Domain of SARS-CoV-2 ORF7a as a Putative Risk Factor in COVID-19

The ongoing COVID-19 pandemic follows an unpredictable evolution, driven by both host-related factors such as mobility, vaccination status, and comorbidities and by pathogen-related ones. The pathogenicity of its causative agent, SARS-CoV-2 virus, relates to the functions of the proteins synthesized intracellularly, as guided by viral RNA. These functions are constantly altered through mutations resulting in increased virulence, infectivity, and antibody-evasion abilities. Well-characterized mutations in the spike protein, such as D614G, N439K, Δ69-70, E484K, or N501Y, are currently defining specific variants; however, some less studied mutations outside the spike region, such as p. 3691 in NSP6, p. 9659 in ORF-10, 8782C > T in ORF-1ab, or 28144T > C in ORF-8, have been proposed for altering SARS-CoV-2 virulence and pathogenicity. Therefore, in this study, we focused on A105V mutation of SARS-CoV-2 ORF7a accessory protein, which has been associated with severe COVID-19 clinical manifestation. Molecular dynamics and computational structural analyses revealed that this mutation differentially alters ORF7a dynamics, suggesting a gain-of-function role that may explain its role in the severe form of COVID-19 disease.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:10

Enthalten in:

Biology - 10(2021), 12 vom: 05. Dez.

Sprache:

Englisch

Beteiligte Personen:

Lobiuc, Andrei [VerfasserIn]
Șterbuleac, Daniel [VerfasserIn]
Sturdza, Olga [VerfasserIn]
Dimian, Mihai [VerfasserIn]
Covasa, Mihai [VerfasserIn]

Links:

Volltext

Themen:

Journal Article
Molecular dynamics
ORF7a
Protein modeling
RMSF
Viral mutation

Anmerkungen:

Date Revised 29.12.2021

published: Electronic

Citation Status PubMed-not-MEDLINE

doi:

10.3390/biology10121276

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM334790972