Clinical, molecular, and epidemiological characterization of the SARS-CoV-2 virus and the Coronavirus Disease 2019 (COVID-19), a comprehensive literature review

Abstract

Coronaviruses are an extensive family of viruses that can cause disease in both animals and humans. The current classification of coronaviruses recognizes 39 species in 27 subgenera that belong to the family Coronaviridae. From those, at least 7 coronaviruses are known to cause respiratory infections in humans. Four of these viruses can cause common cold-like symptoms. Those that infect animals can evolve and become infectious to humans. Three recent examples of these viral jumps include SARS CoV, MERS-CoV and SARS CoV-2 virus. They are responsible for causing severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and the most recently discovered coronavirus disease during 2019 (COVID-19). COVID-19, a respiratory disease caused by the SARS-CoV-2 virus, was declared a pandemic by the World Health Organization (WHO) on 11 March 2020. The rapid spread of the disease has taken the scientific and medical community by surprise. Latest figures from 20 May 2020 show more than 5 million people had been infected with the virus, causing more than 330,000 deaths in over 210 countries worldwide. The large amount of information received daily relating to COVID-19 is so abundant and dynamic that medical staff, health authorities, academics and the media are not able to keep up with this new pandemic. In order to offer a clear insight of the extensive literature available, we have conducted a comprehensive literature review of the SARS CoV-2 Virus and the Coronavirus Diseases 2019 (COVID-19).

Keywords: COVID-19; Coronavirus; Pandemic; Review; SARS-CoV-2.

Fig. 1

Cumulative number of confirmed cases in the world from their first reporting day to day 87.

Fig. 2

Cumulative number of confirmed deaths in the world from their first reporting day to day 87.

Fig. 3

Overall structure and mechanism of infection of SARS-CoV-2. A) Structure and mechanism of infection of the novel coronavirus into human cells through the spike glycoprotein, the ACE2 receptor protein, and the CD147 receptor. The structure of the spike glycoprotein was taken from RCSB PDB 6VXX according to Walls et al. (Zhang et al., 2020a); the structure of the ACE2-BoAT1 complex was taken from RCSB PDB 6M17 according to Yan et al. (Zhou et al., 2020a); lastly, the structure of the main protease (Mpro) was taken from RCSB PDB 6Y84 according to Zhang et al. (Lu et al., 2020). B) Genomic structure and proteins encoded by SARS-CoV-2. C) Genomic structure and proteins encoded by SARS-CoV-2. D) Most frequent amino acid replacements in genomes analyzed worldwide.

Fig. 4

. SARS-CoV-2 replication cycle and its inhibitors. SARS-CoV-2 infection begins with the attachment of the spike (S) protein with the host cell receptor. Two cellular receptors have been identified for SARS-CoV-2 so far: angiotensin-converting enzyme 2 (ACE2) and CD147. After receptor interaction, the cleavage of S protein by the cell surface-associated transmembrane protease serine 2 TMPRSS2 promotes the fusion of viral and cell membranes. Following the release of the nucleocapsid to the cytoplasm, the viral genomic RNA is translated through ribosomal frameshifting to produce polyproteins pp1a and pp1ab, which undergo cotranslational proteolytic processing into the 15 non-structural proteins (nsp1-nsp10 and nsp12-nsp16) that form the replication-transcription complex (RTC). The RTC is involved in the genomic RNA replication and in the transcription of a set of nested subgenomics mRNAs required to express the structural and accessory protein genes. New virions are assembled by budding into the intracellular membranes of the ER-Golgi intermediate compartment membranes and released through exocytosis. Additionally, there are detailed host-based treatment options in blue and viral-based treatment options in pink.

Fig. 5

qRT-PCR primer-probe set positions listed by WHO. USA CDC (2019-nCoV_N1, N2, and N3), the University of Hong Kong (HKU-N and HKU-ORF1b_nsp14), Charité universitätsmedizin Berlin establishment of virology in Germany (RdRp_SARSr and E), National Institute of Health in Thailand (WH-NIC N), National Institute of Infectious Disease in Japan (NIID_2019-nCoV_N), China CDC (N and Orf1ab), Institut Pasteur, Paris, France (nCoV_IP2, IP4 and E). E: envelope protein gene, S: spike protein gene; N: nucleocapsid protein gene. Nsp14: non-structural protein 14 gene, Orf1: open reading frame 1; RdRp: RNA-dependent RNA polymerase gene; The number below amplicons are genome positions as listed in SARS-CoV-2, GenBank MN908947.3

Fig. 6

Clinical features of patients with COVID-19.

Fig. 7

Strategies used or proposed for COVID-19 vaccine development and delivery. A) and B) Adenoviral and measles recombinant viral vectors can be manipulated to express and therefore elicit robust immune responses against the Spike (S) protein of SARS-CoV-2. Recombinant subunit vaccine strategies use the Sf9-baculovirus insect cell expression system resulting in the production of high-quality antigen that can be used to elicit immune responses. D) Purified antigen vaccine strategies implicate the replication of large numbers of virus in cell cultures and the subsequent purification of viral antigens to be used for vaccination. E) Attenuated vaccines contain whole pathogen that has been submitted to heat or chemical treatment inactivation. F) Attenuated live pathogen vaccine strategies consist in administering a live pathogen that due to cell culture passaging has lost its virulence. They usually elicit robust and long-term memory immune responses without the need to administer an adjuvant. G) In DNA vaccines the DNA codifying a highly immunogenic antigen is administered and captured by professional antigen presenting cells (APCs) leading to antigen production and presentation by these cells. H) Moderna's vaccine candidate already in Phase I clinical trials uses an mRNA vaccine approach whereby the genetic information codifying for the S protein of SARS-CoV-2 is delivered in LNPs to enhance absorption by APCs. Once uptaken by APCs the mRNA induces the expression of S antigen that is subsequently mounted on and presented by MHC molecules to elicit adaptive immune response.