Evaluation of the determinants of pandemic potential in the genome of zoonotic coronaviruses

Date of Completion

2022

Document Type

Thesis

Degree Name

Bachelor of Science in Pharmacy

Keywords

SARS-CoV-2, SARS-CoV, MERS-CoV, pandemic potential, host plasticity, emerging infectious diseases

Abstract

Background and Objectives: Zoonotic pathogens with the ability of spillover and human-to-human transmission have resulted in outbreaks including coronavirus disease 2019 (COVID-19) pandemic. Future pandemics might be caused by viruses with similar characteristics as severe acute respiratory syndrome–associated coronavirus 2 (SARS- CoV-2), causative agent of COVID-19. As viral genome provides information on structure and function of viruses, this study aimed to use sequence homology with SARS-CoV-2 and its variants to find the genetic determinants of pandemic potential of known zoonotic coronaviruses.

Methods: SARS-CoV-2 (NC_045512.2) genes related to infectivity, transmissibility, virulence, disease severity, and evasion of host’s immune response were identified by reviewing publications in NCBI PubMed database. These were aligned to REFSEQ genomes of zoonotic and human coronaviruses that were available in NCBI Taxonomy database. NCBI BLAST programs, blastx and tblastn, were used to determine sequence identity (%ID) between known SARS-CoV-2 genes and genomes of other coronaviruses. Principal component analysis (PCA) was conducted using the generated %ID to identify coronaviruses having similar genomic characteristics as SARS-CoV-2. Mutability and host plasticity were determined by identifying sequence homology between nsp14 and receptor-binding domain (RBD) and locating specific mutations in the coronaviruses that were most similar to SARS-CoV-2.

Results and Discussion: Betacoronavirus showed the highest %ID with most SARS- CoV-2 genes contributing to infectivity, transmissibility, virulence, disease severity, and evasion of host’s immune response. Approximately 84% of the observed variations among %ID with SARS-CoV-2 genes can be explained by two principal components (PC1, 76% and PC2, 8.2%). Genes having significant contribution to variances observed in the PCs were identified including nsp 5, nsp 14, and nsp 15. Most genes contribute to immune evasion and viral replication. All Betacoronavirus species shared above-average amino sequence identity with the SARS-CoV-2 Nsp14. The mean amino acid identity of the coronaviruses was 53.91% ± 8.67. However, only the following species have significantly higher sequence identity with Nsp14 (in decreasing order): SARS-CoV Tor2 (NC_004718.3), Bat Hp-betacoronavirus Zhejiang 2013 (NC_025217.1), Hedgehog CoV (NC_039207.1), Betacoronavirus England 1 (NC_038294.1), and MERS-CoV (NC_019843.3). Nsp14 has a 3’-5’-exoribonuclease activity essential for proofreading. Detailed analyses of the common mutation sites in SARS-CoV-2 and their presence in other coronaviruses at homologous provided insight to their mutability and host plasticity.

Conclusion: Preliminary prediction of pandemic potential of some zoonotic coronavirus species was done by sequence alignment of known SARS-CoV-2 genes with genomes of other coronaviruses and PCA. Surveillance of these zoonotic coronaviruses needs to be done to prepare for next emerging infectious disease.

First Advisor

Sigfredo B. Mata

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