Researchers analyse genomic determinants of coronavirus pathogenicity

Washington DC. [USA]: A recent analysis led by a team of researchers found crucial genomic features that are unique to SARS-CoV-2, the virus that causes COVID-19, and two other deadly coronaviruses, SARS-CoV and MERS-CoV.
Published in PNAS, the research reports that these features correlate with the high fatality rate of these coronaviruses as well as their ability to switch hosts from animals to humans.

They identified features that could represent crucial elements of coronavirus virulence and allow for detecting animal coronaviruses that have the potential to make the jump to humans in the future.

Using an integrated approach that included machine-learning and comparative genomics, authors Ayal B. Gussow, Noam Auslander, Guilhem Faure, Yuri I. Wolf, Feng Zhang, and Eugene V. Koonin identified three previously undetected likely determinants of pathogenicity and zoonotic transmission.

These features include enhancement of the nuclear localization signals (NLS) in the nucleocapsid protein and distinct inserts in the spike glycoprotein that appears to be associated with a high case fatality rate of these coronaviruses as well as the host switch from animals to humans.

The identified features could be crucial contributors to coronavirus pathogenicity and possible targets for diagnostics, prognostication, and interventions.

The enhancement of the NLS in the three coronaviruses that can cause severe diseases (hereafter high-CFR coronaviruses) ) nucleocapsids implies an important role of the subcellular localization of the nucleocapsid protein in coronavirus pathogenicity.

Strikingly, insertions in the spike protein appear to have been acquired independently by the SARS and MERS clades of the high-CFR coronaviruses, in both the domain involved in virus-cell fusion and the domain mediating receptor recognition.

The gradual enhancement of the NLS in the nucleocapsids and the different insertions in the spike protein of the high-CFR coronaviruses imply that these changes do not reflect a single event that occurred in the common ancestor, but rather a convergent trend in the evolution of the high-CFR viruses.

These insertions, most likely, enhance the pathogenicity of the high-CFR viruses and contribute to their ability to zoonotically transmit to humans.

All of these features are shared by the high-CFR coronaviruses and their animal (in particular, bat) infecting relatives in the same clade, which demonstrates that the emergence of SARS-CoV-2 is a natural part of the ongoing coronavirus evolution and is compatible with the possibility of future zoonotic transmission of additional highly pathogenic strains to humans.

The predictions made through this analysis unveil potential critical features in the mechanism of SARS-CoV-2 virulence and its evolutionary history, are amenable to straightforward experimental validation and could serve as predictors of strains pathogenic to humans. 

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