Statistical analysis supports UTR (untranslated region) deletion theory in SARS-CoV-2

ABSTRACT

It was noticed that the mortality rate of SARS-CoV-2 infection experienced a significant declination in the early stage of the epidemic. We suspect that the sharp deterioration of virus toxicity is related to the deletion of the untranslated region (UTR) of the virus genome. It was found that the genome length of SARS-CoV-2 engaged a significant truncation due to UTR deletion after a mega-sequence analysis. Sequence similarity analysis further indicated that short UTR strains originated from its long UTR ancestors after an irreversible deletion. A good correlation was discovered between genome length and mortality, which demonstrated that the deletion of the virus UTR significantly affected the toxicity of the virus. This correlation was further confirmed in a significance analysis of the genetic influence on the clinical outcomes. The viral genome length of hospitalized patients was significantly more extensive than that of asymptomatic patients. In contrast, the viral genome length of asymptomatic was considerably longer than that of ordinary patients with symptoms. A genome-level mutation scanning was performed to systematically evaluate the influence of mutations at each position on virulence. The results indicated that UTR deletion was the primary driving force in alternating virus virulence in the early evolution. In the end, we proposed a mathematical model to explain why this UTR deletion was not continuous.

KEYWORDS:

• SARS-COV-2
• deletion of the untranslated region
• nucleic acid degradation system
• viral toxicity

Acknowledgments

We thank Dr. Dongqing Wei from Shanghai Jiao Tong University (China) for fruitful initial discussions Dr. Zuyi Huang from Villanova University (US) for helpful conversations, comments, and clarifications.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

Conceptualization, Z.X. and J.D.; methodology, Z.X.; validation, Z.X.; formal analysis, Z.X and D.Y.; investigation, D.Y.; resources, J.D.; data curation, D.Y and L.W.; writing – original draft preparation, Z.X.; writing – review and editing, J.D.; supervision, J.D.; funding acquisition, Z.X. All authors have read and agreed to the published version of the manuscript.

Data availability statement

The data presented in this study are available in the supplementary materials.

Additional information

Funding

This research was funded by DeZhou University, grant number 30101418