Coronavirus Disease Pandemic (COVID-19): Challenges and a Global Perspective

Abstract

The technology-driven world of the 21^st century is currently confronted with a major threat to humankind, represented by the coronavirus disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome, coronavirus-2 (SARS-CoV-2). As of now, COVID-19 has affected more than 6 million confirmed cases and took 0.39 million human lives. SARS-CoV-2 spreads much faster than its two ancestors, SARS-CoV and Middle East respiratory syndrome-CoV (MERS-CoV), but has low fatality rates. Our analyses speculate that the efficient replication and transmission of SARS-CoV-2 might be due to the high-density basic amino acid residues, preferably positioned in close proximity at both the furin-like cleavage sites (S1/S2 and S2') within the spike protein. Given the high genomic similarities of SARS-CoV-2 to bat SARS-like CoVs, it is likely that bats serve as a reservoir host for its progenitor. Women and children are less susceptible to SARS-CoV-2 infection, while the elderly and people with comorbidities are more prone to serious clinical outcomes, which may be associated with acute respiratory distress syndrome (ARDS) and cytokine storm. The cohesive approach amongst researchers across the globe has delivered high-end viral diagnostics. However, home-based point-of-care diagnostics are still under development, which may prove transformative in current COVID-19 pandemic containment. Similarly, vaccines and therapeutics against COVID-19 are currently in the pipeline for clinical trials. In this review, we discuss the noteworthy advancements, focusing on the etiological viral agent, comparative genomic analysis, population susceptibility, disease epidemiology and diagnosis, animal reservoirs, laboratory animal models, disease transmission, therapeutics, vaccine challenges, and disease mitigation measures.

Keywords: COVID-19; Coronavirus; SARS-CoV-2; diagnosis; pandemic; pathobiology; therapeutics; vaccines.

Figure 1

The timeline of significant events of COVID-19 caused by SARS-CoV-2. Major events, starting from the first report of novel CoV from Wuhan, China—including the declaration of COVID-19 as a worldwide pandemic by the WHO, and the situation as of June 7, 2020—have been depicted in the timeline format.

Figure 2

Genome organization of SARS-CoV-2 and its comparison with other coronaviruses. The coding regions of beta-CoVs, SARS-CoV-2 Wuhan-HU-1 (NC_045512.2; 29,903 bps), bat SARS-like-CoVZC45 (MG772933.1; 29,802 bps), human SARS-CoV Tor2 (AY274119.3; 29,751 bps), MERS-CoV EMC (NC_019843.3; 30,119 bps), bovine CoV ENT (NC_003045.1; 31,028 bps), and a delta-CoV, the porcine CoV HKU15 (NC_039208.1; 25425 bps) are presented. The genomes consist of a 5′ untranslated region (5′ UTR), an open reading frame (ORF 1a/ab) encoding non-structural proteins (nsps), structural proteins, hemagglutinin–esterase, spike (S), membrane (M), envelope (E), and nucleocapsid (N) proteins, several accessory proteins, and a 3′ untranslated region (3′ UTR). The lengths of the ORFs, nsps, and accessory proteins are not drawn to scale.

Figure 3

Comparative sequence and structural analyses of the SARS-CoV-2 spike protein. (A) The cleavage sites of SARS-CoV-2 spike proteins (S1/S2 and S’ protease cleavage sites) and their comparison with those in other coronaviruses. The superimposition of the receptor-binding domain (RBDs) of SARS-CoV-2 (pdb: 6VSB) on (B) human SARS-CoV (pdb: 2AJF), (C) MERS-CoV (pdb: 4KR0), (D) BtCoV-HKU4 (pdb: 4QZV), and (E) HCoV-NL63 (pdb: 3KBH). (F) The superimposition of the RBDs of porcine respiratory CoV (pdb: 4F5C) on HCoV-NL63 (pdb: 3KBH). RMSD: Root Mean Square Deviation. UCSF Chimera was used for the superposition and visualization of the RBDs of the different CoVs [40].

Figure 4

Maximum likelihood tree of Betacoronaviruses, including SARS-CoV-2. The phyloanalysis included SARS-CoV-2 originating from China, the USA, Australia, Japan, and South Korea. Different subgenera of Betacoronaviruses have been labeled with different colors according to the color legend on the left side of the tree. Major species of each subgenus have been depicted in front of each clade.

Figure 5

Worldwide distribution map depicting COVID-19 cases and deaths in major world regions. Six regions have been described by the WHO where the COVID-19 disease is present and are depicted on the map along with confirmed cases and deaths represented as of June 7, 2020.