Coronavirus: An Overview
Coronaviruses (CoVs) consist of a group of enveloped, non-segmented, positive-sense single-stranded RNA viruses from the order Nidovirales, family Coronaviridae, and subfamily Orthocoronavirinae. Coronaviruses have the largest genome of all RNA viruses, encoding viral proteins involved in transcribing viral RNA, replication, structure, and accessory proteins (15). The virus has four main proteins – spike, envelope, membrane, and nucleocapsid (S, E, M, and N, respectively) – important for the virus to enter and replicate in the host cell (16), also representing the main molecules used for diagnosis, antiviral treatment, and potential vaccines.
According to antigenic and genetic criteria, CoVs are classified into three groups: α-CoVs, β-CoVs and γ-CoVs (17). Coronaviruses of human infection (hCoVs) are detected in both α-CoVs (hCoV-229E and NL63) and β-CoVs (MERS-CoV, hCoV-OC43, hCoV-HKU1, SARS-CoV-1, and SARS-CoV-2) (18). In addition to infecting humans, α-CoVs and β-CoVs can infect several species of mammals, including bats and pigs, while γ-CoVs infects birds, wild cats, pigs, and some species of marine mammals (19–22). CoVs have a high potential of jumping between species and their genome is characterized by high-frequency recombination and a high mutation rate (23).
hCoVs are responsible for the common cold and other respiratory pathologies with different degrees of severity, especially in babies, the elderly, and immunocompromised patients, characterized by human-to-human transmission (24). Coronavirus severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) (25–27) are caused by human β-CoVs and represent a serious illness with a case-fatality ratio of 9 - 10% and 35%, respectively (8, 28).
In contrast, according to data provided by the WHO, COVID-19 caused by SARS-CoV-2 shows an estimated lethality of ~5% of reported cases (data reported until July 2020) (29), reaching rates of up to 15% among elderly patients and patients with comorbidities. Despite the lower case-fatality rate, the high viral transmissibility of SARS-CoV-2 generates an overall number of cases that far outweighs SARS or MERS for spreading more easily among people (5, 28).
The first report of a COVID-19 case in Wuhan, China, occurred in December 2019, and in February the WHO declared the matter a public health emergency of international concern. Until now (September 2020), reports of COVID-19 account for almost 30 million cases and more than 900 thousand deaths in more than 220 countries, territories, or areas (1, 29). Imperial College, UK (30) proposed a mathematical model whose prospects indicate 7 billion infections and 40 million deaths in 2020 in the absence of mitigation measures.
Both SARS-CoV and MERS-CoV were initially believed to have resulted from a zoonotic spread from a bat population (31). α-CoVs and β-CoVs are believed to have evolved over thousands of years, restricted to bats and intermediate mammalian hosts (civet cats for SARS-CoV-1 and dromedary camels for MERS-CoV), which probably contributed to the zoonotic transmission of the new coronavirus to humans (32).
Regarding SARS-CoV-2 transmission, several works have demonstrated that coronaviruses found in pangolins (Manis javanica) and SARS-CoV-2 share a genomic similarity of approximately 91%. The presence of the virus in samples of pulmonary fibrosis in pangolins found around the COVID-19 outbreak suggests that these animals were the hosts responsible for spreading the virus among humans (4, 21, 33). In contrast, some researchers claim that SARS-CoV-2 did not come directly from pangolins since, despite their similarity, the viruses found in these animals do not have the essential tools needed to infect human cells (4, 34). Thus, the possibility of other animals, such as ferrets and snakes, acting as intermediate hosts for SARS-CoV-2 and being responsible for zoonotic transmission is still under consideration (35).
Since SARS-CoV-2 genomes’ information is still scarce and genomes of other coronaviruses closely related to this virus have limited availability (36), the evolutionary origin of SARS-CoV-2 is yet to be fully understood. So far, it is known that, compared with other β-CoVs, SARS-CoV-2 shows 50, 79, and 88 - 96% of genome similarity with MERS-CoV, SARS-CoV-1, and the bat SARS-like virus, respectively (37, 38).
The genomic changes of SARS-CoV-2 appear in both non-structural and structural proteins – notably in proteins S, M, and N – affecting viral multiplication, encapsulation, tropism, and transmission (39). Two important characteristics were described in the genome of SARS-CoV-2 that lead to alterations in the S protein: (i) receptor-binding domain (RBD), which is the most variable part of the viral genome, appears to be optimized for binding to the human ACE2 receptor, and (ii) presence of a polybasic (furin) cleavage site at the S1 and S2 boundary, via the insertion of twelve nucleotides, which allows effective cleavage by furin and other proteases and has a role in determining viral tropism, infectivity, and host range (4).
Such genomic changes also affected the recognition of these viruses by immune cells. Baruah and Bose (40) demonstrated that Sars-CoV-2 has specific regions for B cell and cytotoxic T cell glycoproteins recognition, which does not coincide with those found in bat-derived CoV, SARS-CoV-1, or MERS-CoV ( Figure 1 ). Such distinguished interaction of cells and viruses can promote unusual immunomodulation or immune responses that contribute to the severity of the disease. All aspects of immunomodulation and immune evasion will be discussed in the subsequent topics.
Figure 1  Genetic evolution of SARS-CoV-2 and its consequences. Compared with other β-CoVs, SARS-CoV-2 has similarities of 50, 79, and 88 - 96% to MERS-CoV, SARS-CoV-1, and bat SARS-like-CoV genome, respectively, with 91% similarity with SARS-like CoV found in pangolins. The virus resulted from mutations that caused changes in important proteins for its virulence; notably, the spike, matrix, envelope, and nucleocapsid proteins caused alterations in host cell interactions, which culminated in a new aggressive disease (COVID-19). RBD (receptor binding domain), S1 (subunit 1) S2 (subunit 2).