From SARS to SARS-CoV-2, insights on structure, pathogenicity and immunity aspects of pandemic human coronaviruses

Abstract

Human Coronaviruses (HCoV), periodically emerging across the world, are potential threat to humans such as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) - diseases termed as COVID-19. Current SARS-CoV-2 outbreak have fueled ongoing efforts to exploit various viral target proteins for therapy, but strategies aimed at blocking the viral proteins as in drug and vaccine development have largely failed. In fact, evidence has now shown that coronaviruses undergoes rapid recombination to generate new strains of altered virulence; additionally, escaped the host antiviral defense system and target humoral immune system which further results in severe deterioration of the body such as by cytokine storm. This demands the understanding of phenotypic and genotypic classification, and pathogenesis of SARS-CoV-2 for the production of potential therapy. In lack of clear clinical evidences for the pathogenesis of COVID-19, comparative analysis of previous pandemic HCoVs associated immunological responses can provide insights into COVID-19 pathogenesis. In this review, we summarize the possible origin and transmission mode of CoVs and the current understanding on the viral genome integrity of known pandemic virus against SARS-CoV-2. We also consider the host immune response and viral evasion based on available clinical evidences which would be helpful to remodel COVID-19 pathogenesis; and hence, development of therapeutics against broad spectrum of coronaviruses.

Keywords: Angiotensin-converting enzyme 2; COVID-19; Cytokine storm; Human coronaviruses; Interferons; Interleukin.

Graphical abstract

Fig. 1

The taxonomic (a) classification and positions for the known seven HCoVs, and (b) phylogenetic tree analysis of CoVs constructed based on S gene using Molecular Evolutionary Genetics Analysis 6 software under neighbor-joining method and 1000 bootstrap values (Biswas et al., 2020).

Fig 2

Schematic representation of three HCoVs, viz. SARS-CoV, MERS-CoV, and SARS-CoV-2, transmission to human from bat through intermediate hosts.

Fig. 3

A typical structure of CoV (80-120 nm) exhibiting various structural proteins, i.e. S, M, E, and genomic RNA packed inside the particle by N protein.

Fig. 4

Schematic representation for (a) genome organization and (b) functional domains in the genome of SARS-CoV, MERS-CoV, and SARS-CoV-2.

Fig. 5

Schematic representation for HCoVs attachment and entry into airway cells. The envelope spike glycoprotein binds to its cellular receptor ACE2 for SARS-CoV and DPP4 for MERS-CoV.

Fig. 6

An overview for the life cycle of HCoVs in the host-cell (Song et al., 2019; Zumla et al., 2015)

Fig. 7

Cytokine pathogenesis of coronavirus disease (Yi et al., 2020).

Fig. 8

Possible mechanisms of SARS-CoV-2-mediated inflammatory responses based on previous study of SARS-CoV (Fu et al., 2020).