SARS-CoV-2 outbreak: role of viral proteins and genomic diversity in virus infection and COVID-19 progression

Abstract

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is the cause of coronavirus disease 2019 (COVID-19); a severe respiratory distress that has emerged from the city of Wuhan, Hubei province, China during December 2019. COVID-19 is currently the major global health problem and the disease has now spread to most countries in the world. COVID-19 has profoundly impacted human health and activities worldwide. Genetic mutation is one of the essential characteristics of viruses. They do so to adapt to their host or to move to another one. Viral genetic mutations have a high potentiality to impact human health as these mutations grant viruses unique unpredicted characteristics. The difficulty in predicting viral genetic mutations is a significant obstacle in the field. Evidence indicates that SARS-CoV-2 has a variety of genetic mutations and genomic diversity with obvious clinical consequences and implications. In this review, we comprehensively summarized and discussed the currently available knowledge regarding SARS-CoV-2 outbreaks with a fundamental focus on the role of the viral proteins and their mutations in viral infection and COVID-19 progression. We also summarized the clinical implications of SARS-CoV-2 variants and how they affect the disease severity and hinder vaccine development. Finally, we provided a massive phylogenetic analysis of the spike gene of 214 SARS-CoV-2 isolates from different geographical regions all over the world and their associated clinical implications.

Keywords: COVID-19; Clinical implications; Mutation; SARS-CoV-2; Spike Protein; Variants.

Fig. 1

Schematic diagram showing the viral particle structure of SARS-CoV-2 (A), and the genome organization of SARS-CoV-2 genes (B). The structural components of the spike (S) protein; S2 contains signal peptide (SP), N-terminal domain (NTD), and receptor binding domain (RBD). The S1 contains fusion peptide (FP), heptad repeat domains (HR1 and HR2), trans-membrane domain (TMD) and cytoplasmic domain (CD). The arrowhead indicated the furin and TMPRSS2 cleavage sites. (B) The genome organization of SARS-CoV-2 genes

Fig. 2

The phylogenetic analysis of the full spike (S) protein genes coding region of 214 SARS-CoV-2 sequences deposited in GenBank from various countries all over the world. The tree was constructed using the maximum-likelihood method in the MEGA6 software. The evolutionary distances were computed by General Time Reversible model and bootstrap 1,000 replicates with complete deletion of the gap and missing data. The SARS-CoV-2 sequences from Wuhan, China (blue), bat RaTG13 (pink), mink (green) and Egypt (red). The accession numbers, source of sequence, date and country of origin are shown in the sequence labels