The putative metal-binding proteome of the Coronaviridae family.

Metalloproteins are well-known for playing various physicochemical processes in all life forms, including viruses. Some life-threatening viruses (such as some members of the Coronaviridae family of viruses) are emerged and remerged frequently and are rapidly transmitted throughout the globe. This study aims to identify and characterize the metal-binding proteins (MBPs) of the Coronaviridae family of viruses and further provides insight into the MBP's role in sustaining and propagating viruses inside a host cell and in the outer environment. In this study, the available proteome of the Coronaviridae family was exploited. Identified potential MBPs were analyzed for their functional domains, structural aspects, and subcellular localization. We also demonstrate phylogenetic aspects of all predicted MBPs among other Coronaviridae family members to understand the evolutionary trend among their respective hosts. A total of 256 proteins from 51 different species of coronaviruses are predicted as MBPs. These MBPs perform various key roles in the replication and survival of viruses within the host cell. Cysteine, aspartic acid, threonine, and glutamine are key amino acid residues interacting with respective metal ions. Our observations also indicate that the metalloproteins of this family of viruses circulated and evolved in different hosts, which supports the zoonotic nature of coronaviruses. The comprehensive information on MBPs of the Coronaviridae family may be further helpful in designing novel therapeutic metalloprotein targets. Moreover, the study of viral MBPs can also help to understand the roles of MBPs in virus pathogenesis and virus-host interactions.

A SARS-CoV-2 -human metalloproteome interaction map.

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 Zn2+ 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.