A SARS-CoV-2 –human metalloproteome interaction map

Abstract

The recent pandemic caused by the novel coronavirus resulted in the greatest global health crisis since the Spanish flu pandemic of 1918. There is limited knowledge of whether SARS-CoV-2 is physically associated with human metalloproteins. Recently, high-confidence, experimentally supported protein-protein interactions between SARS-CoV-2 and human proteins were reported. In this work, 58 metalloproteins among these human targets have been identified by a structure-based approach. This study reveals that most human metalloproteins interact with the recently discovered SARS-CoV-2 orf8 protein, whose antibodies are one of the principal markers of SARS-CoV-2 infections. Furthermore, this work provides sufficient evidence to conclude that Zn 2+ plays an important role in the interplay between the novel coronavirus and humans. First, the content of Zn-binding proteins in the involved human metalloproteome is significantly higher than that of the other metal ions. Second, a molecular linkage between the identified human Zn-binding proteome with underlying medical conditions that might increase the risk of severe illness from the SARS-CoV-2 virus has been found. Likely perturbations of host cellular metal homeostasis by SARS-CoV-2 infection are highlighted.

An Issue of Concern: Unique Truncated ORF8 Protein Variants of SARS-CoV-2

“…ORF8 suppresses type I interferon antiviral responses and interacts with host factors involved in pulmonary inflammation and fibrogenesis [15,16]. From all viral proteomes interacting with human metalloproteome, the ORF8 interplay with 10 out 58 [17]. ORF8 (of SARS-CoV-2 and SARS-CoV) play crucial roles in virus pathophysiological events, it dysregulates the TGF-β pathway, which is involved in tissue fibrosis [18].…”

Trace element homeostasis in the neurological system after SARS-CoV-2 infection: Insight into potential biochemical mechanisms

“…In this sense, Cu has a promising role to prevent and treat the viral activity of SARS-CoV-2 which is an enveloped virus, non-segmented, spherical, with a single RNA strand and a spike glycoprotein covered by a phospholipid bilayer [89] . This morphological structure of the novel COVID-19 has mediated its trapping and inactivation through copper-based materials such as laponite-Cu 2+ nanocoating on filter membranes, CuS impregnated or copper film coating on fiber masks, nanohybrid formulation and surfaces of Cu-Ag [90] , [91] , [92] , [93] . These materials trap the novel coronavirus through bound to the spike protein and inactivate it, promoting irreversible damage to the virus genome and morphology including disruption of envelope and dispersal of spike surface [16] .…”

Zn‐Induced Interactions Between SARS‐CoV‐2 orf7a and BST2/Tetherin

“…These results, besides shedding some light on the selective role of orf7a in the development of the disease could open the way for possible therapeutic strategies against SARS‐CoV‐2 based on the modulation of cellular Zn homeostasis. [ 7 , 9 ]…”

“…It is found that the percentages of Zn, Mg, Fe, Cu, and Mn metalloproteins belonging to the human proteome interacting with the SARS‐CoV‐2 proteins (human SARS‐CoV‐2 metalloproteome) are found to be 12.3 %, 3 %, 1.8 %, 0.3 % and 0.3 %, respectively, with the majority of them (about 17 %) interacting with the accessory protein SARS‐CoV‐2 orf8 [7] . As one can see from these numbers, the fraction of Zn‐binding proteins in the human SARS‐CoV‐2 metalloproteome is significantly higher than that of the other metal ions‐binding proteins.…”

“…Insert the note „For a review describing the whole set of SARS‐CoV‐2 coded proteins see Ref. [5].” A rather complete and accurate study in this direction has been recently reported [6] and it led to the conclusion that the set of human proteins capable of interacting with the SARS‐CoV‐2 proteins is quite diversified [7] and include a large number of metalloproteins. This situation is shared by other DNA and RNA viruses [8] …”