From SARS-CoV to MARS-CoV

Severe acute respiratory syndrome-coronavirus (SARS-CoV) is a viral disease of the respiratory system with zoonotic importance. It was initially reported in Southern China (province: Guangdong) in mid-November (2002). This disease showed a viral spread to more than thirty countries belonging to five different continents and infected 8098 people, out of which 774 died. The emergence of SARS has been found to be due to human-animal contact. SARS-CoV is not harmful in children, and there is no vertical transmission from mothers to newborns. In pediatric age groups, no death has been reported. Most SARS autopsies cases showed extensive spleen and white pulp necrosis with severe depletion of lymphocytes. The genomic sequence of SARS-CoV is detected through RT-PCR in some specimens of the brain and cerebral spinal fluid. The pathogenesis of SARS is very complex as multiple factors are involved. With the prevalence of SARS-CoV, many diseases are associated with and cause damage to different organs and systems of the body. Some strategies that can help treat SARSCoV are host-directed therapies, the use of antibiotics, inhibitors of viral and host proteases, and interferons. The World Health Organization (WHO) issued an alert on 12th March 2003 about new deadly infectious diseases globally. After three days, the WHO named these diseases SARS. China, Singapore, Taiwan, and Hong Kong were the most severely affected areas. 

Coronaviruses (CoVs) are a large and distinct group of RNA viruses that can affect a wide range of animal species. These are spherical-shaped viruses with spike (S) proteins positioned from the virion surface. The severe acute respiratory syndromecoronavirus (SARS-CoV) has a 30 kb RNA genome with 14 open reading frames flanked by 5′ and 3′ UTR sections. The 5′ untranslated region is 265 bp long, while the 3′ end is 342 bp long. Normally, the coronavirus S protein is fragmented into 2 subunits, S1 and S2, though in the context of SARS-CoV, an un-cleaved type one transmembrane S protein with S1 and S2 subunit homology has been discovered. CoVs are classified into four genera based on genetic and antigenic characteristics: α, β, γ, and δ. α and β CoVs only infect mammals, whereas primarily γ and δ infect birds, though some can infect mammals as well. In 29 regions and countries, many deaths and cases were reported due to the outbreak of SARS. Initially, the cases were reported in 2002 in China. In 2003, the outbreak of atypical pneumonia was first time reported by WHO, and five deaths and 306 cases were reported in China due to this outbreak. Molecular epidemiology studies revealed that the virus from the 2002–2003 South China pandemic was distinct from the unique virus isolated in similar areas in the late 2003 and early 2004 epidemics, presenting distinct species-crossing events. SARSCoV has a wide host range. Different studies also showed that this virus can proliferate in ferrets and macaques; however, in cats, no symptoms of this virus were found.

 The coronavirus family is named for the large spike protein molecules found on the pathogen exterior, which give the virus a crown-like appearance, the coronavirus genome is the biggest among RNA viruses. There are about seven viruses capable of infecting humans: in the alpha genus, there are 229E and NL63, and in the beta genus, there are OC-43, HKU1, MERS-CoV, SARS-CoV, and SARS-CoV-2. The severe acute respiratory syndrome coronavirus (SARS-CoV) is a positive-stranded RNA virus. In humans, the virus is transmitted through respiratory tract droplets or discharges from diseased persons. The reservoir hosts for MERS-CoV are camels, while those for SARS-CoV are most likely bats. SARS-CoV-2 infecting a snake may have been transmitted by zoonotic transmission in a palm civet. The Chinese viruses SARS-Co- -2 and SARS-CoV have many things in common, including contact with wild animals.However, both SARS-CoV-2 and MERS-CoV have the ability to persist and spread the illness even when the infected individuals are untreated. SARS-S1 CoV-2's components of the spike proteins have 75% structural commonality with SARS-like CoVs in bats and SARS-CoV. According to genetic comparisons, the latest investigations have proven that SARS-CoV-2 targets angiotensin-converting enzyme type-2 (ACE-2) in humans. However, SARS-CoV-2 possesses an identical receptorbinding domain (RBD) pattern to SARS-CoV, with differences in amino acid sequences at certain vital positions. The RBD is also found in the C-domain S1 component of MERS-CoV's S protein (Spike). Conversely, in contrast to SARS-CoV, MERS-CoV uses a dipeptidyl-peptidase-4 (DPP-4) helix as its binding site. Similarly, MERS-RBD coronaviruses (CoVs) have an extra subdomain that functions as the receptor-binding motif (RBM).

SARS-CoV has an RNA genome that is categorized in the family Coronaviridae and the order Nidovirales. Similarly, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) also belongs to this family and order. A significant degree of variability was observed in SARS-CoV-2 in individuals, which could be influenced by genetic variations in the host. This may impact the progression of sickness and the efficacy of treatment approaches. Individuals who carry certain mutants of genes (ACE2 and TMPRSS) directly linked to viral illness or who have a distinctive expression of those genes may be more vulnerable (SARS-CoV-2). These alterations may explain the enormous diversity of symptoms and severity of Coronavirus Disease-19 (COVID-19)-related disease in various people. Regarding variation, the D614G spikes gene is the most varied among hosts. Moreover, single nucleotide polymorphism (SNP) and single nucleotide variants (SNVs) are causes of host genetic diversity, according to some studies. The structure of SARS-CoV is made up of structural and accessory proteins. These accessory proteins (3a, 3b, 7b, ORF, etc.) show missense mutations in their sequence. Both types of proteins undergo rapid mutations. Point mutations and genetic recombination of SARS-CoV participate in its adaptations and variations among hosts of different species. Middle East Respiratory Coronavirus (MERS-CoV) and SARS-CoV-1, SARS-CoV-2 have striking differences among their proteins. Mannose-binding protein (MBL) takes part in countering viral infections. A decrease in MBL increases the exposure of host cells to SARS-CoV infections.

Severe acute respiratory syndrome-coronavirus (SARS-CoV) is responsible for causing respiratory diseases. Its transmission takes place through saliva droplets. SARS-CoV appeared first in Southern China. It spread quickly across the globe from 2002 to 2003. In the wild, horseshoe bats serve as natural reservoir hosts for SARSCoV. Palm civets show high susceptibility toward SARS-CoV. SARS-CoV gradually mutates on continuous transmission from human to human, animal to animal, and animal to human. These mutational changes can occur in viral proteins, which bind to the angiotensin-converting enzyme2 (ACE2) receptor of the host cell surface and cause infection. The worldwide spread of infection leads to the survival of of fitter, more spreadable variants with enhanced ability to adapt to their host. In this chapter, we discussed the different angles of variation in SARS-CoV and the impact of these variations on viral pathogenicity. During this study, we observed many variations in virus spike protein, variation in amino acid residues, variation in open reading frames, the interaction of spike with host ACE2 receptor, genetic variability with OC43, the impact of the variation in IL-12, RBI, and the variation in serine protease. No proven treatments, cures, or pre-emptive strategies were available for SARA-CoV. Coronaviruses found in bats show genetic diversity, pointing out our poor understanding of viral zoonosis from wild animals. Viral zoonosis can be prevented by considering the concept of “One Health”.

The coronavirus spontaneously mutates and produces new strains overtime. A few variants are more infectious and harmful than others. Additionally, certain variations are capable of eluding treatment control. These modifications may have an impact on the virus's features. The novel variations have the power to progress quickly and induce pathogenicity. Vaccines, diagnostic tools, active compounds, and other precautionary care may also be affected by novel variations. At first, it was considered that cells could also ingest and destroy infections in addition to degrading cellular contents. This mechanism was later confirmed for other viruses and given the label xenophagy. Because of the modification of the coronavirus, poor and emerging nations are constantly confronted with new issues. Developing nations must promptly prepare and create a clear direction to vaccinate their entire population. It has frequently been questioned if vaccination can entirely safeguard someone from a virus that alters its features quickly and produces variations with more powerful alterations. However, much evidence is that immunization prevents the virus from spreading and protects people.

The host’s wide range of genetic variation plays an essential role in determining the susceptibility, severity, and overall pathological conditions of coronavirus disease-19 (COVID-19) following infection with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). COVID-19, caused by SARS-CoV, is a zoonotic disease that has affected humans after crossing boundaries. Emerging viral infections typically result from the host when a virus transfers from the very first host into a new species. There is substantial diversity in illness progress among patients infected with SARS-CoV-2. Many do not show any manifestations, while others progress to acquire COVID-19; nonetheless, the intensity of COVID-19 symptoms substantially ranges among people. Host factors such as age, gender, geographical region, diseases, co-morbidities, and various host genetic factors predispose susceptibility to SARS-CoV-2 infection. Individuals who possess certain variations of genes directly implicated in viral infection (e.g., ACE2, TMPRSS2) or who have differential expression of those genes may be more susceptible to SARS-CoV-2. These alterations might account for the wide variety of symptoms and severity of COVID-1- -related SICKNESS in various people. Because the behavior of the infectious agent varies so much across strains, the impacts of individual variation are best evident when the same strain of an organism infects previously unexposed people simultaneously. An increase in genetic diversity in host sensitivity to pathogenic agents has been related to the development of major-effect resistance polymorphisms among populations.

The Middle East respiratory syndrome-coronavirus (MERS-CoV) is a rising threat to the whole world’s health security. It is considered a new epidemic. It is a fatal respiratory disease with an elevated death rate. In humans, it produces low respiratory tract infections. The virus originated from bats but serological studies were conducted. The evidence of the studies proved that the antibodies of the MERS-CoV were reported in the camels of the Middle Eastern countries that first tested positive for the virus. Thus, these camels were considered the hosts of the MERS-CoV. MERS-CoV may be an animal disease virus that may cause secondary human infections. Camelus dromedarius camels are known as the host. Symptoms include fever (98%), shortness of breath (72%), cough (83%), and myalgia (32%). Other symptoms were also seen: 26% of patients had diarrhea and 21% had vomiting. Diagnosis consists of nasopharyngeal swabs, sputum, tracheal aspirates, and broncho alveolar lavage. There is no vaccine or specific treatment for MERS-CoV, although many vaccines and treatments for the virus are being developed. The patient's health condition determines the type of treatment. The ongoing advancement of technologies to systematically and reliably diagnose asymptomatic MERS-CoV infections will shed light on the virus's true prevalence in the human population.

The Middle East respiratory syndrome (MERS-CoV) is a betacoronavirusborne acute viral illness. Since it first appeared in 2012, multiple cases of animal-t- -human transmission of MERS-CoV have been observed, indicating that MERS-CoV has the potential to cause a widespread epidemic. It has been detected in bronchial samples from more than 27 countries, with approximately 2,505 reported cases and a mortality rate of 36%. Genetic heterogeneity of MERS-CoV between different samples may have paved the way for cross-species transmission and changes in the tropics between species and within species. MERS-CoV has many evolutionary genomic origins in spike protein, envelope protein, matrix, and non-structural proteins (nsps) and mutates continuously. In this chapter, we highlighted the causes and significance of mutation in the amino acid sequences of spike protein, envelop protein, matrix protein, nucleocapsid protein, and snp. Among the most enduring obstacles in controlling coronavirus disease is the evolution of the virus, which is influenced by genetic diversity, mutation, and natural selection.

Middle East respiratory syndrome coronavirus (MERS-CoV) is a potentially fatal disease that can be passed from animals to humans. It was first discovered in numerous Arab countries in 2012, including Jordan and Saudi Arabia. Over 2500 people have been impacted by this illness worldwide, with 850 confirmed deaths from 27 nations. Humans, camels, sheep, goats, bats, pigs, rabbits, bovines, horses, and alpacas have all been infected with MERS-CoV worldwide. MERS-CoV keeps a 32 kb positive-sense RNA genome with at least six pathogenic components, including ORF1ab, membrane, envelope, spike, and nucleocapsid. The spike protein promotes virus entrance across the host cell membrane. To initiate the disease, host proteolytic enzymes must separate the MERS-CoV spike protein into two components, S1 and S2. The spike protein receptor-binding domain (RBD) binds to host cell receptors such as dipeptidyl peptidase 4, sialic acid, GRP78, and CEACAM5, which are found on the host cell membrane surface. There is little information available about MERS-CoV infection host genetic diversity. This chapter emphasizes the importance of data related to historical background, host characteristics, the molecular diversity of MERS-CoV host cell entry receptors, and the genetic diversity of MERS-CoVs in bat, human, camel, and civet hosts. These findings will help us better understand the host genetic diversity of MERS-CoV infection.

The Middle East Respiratory Syndrome (MERS-CoV) coronavirus is an infectious viral disease. It has emerged rapidly from Saudi Arabia and later spread to other countries. MERS-CoV resulted in a 35% case fatality rate and became a global public health priority. The MERS-CoV has been heavily endemic in dromedary camel populations of the Middle East and belongs to the 2C lineage of beta-CoV. This virus expresses the dipeptidyl peptidase 4 (DPP4) receptor and causes severe acute respiratory syndrome in humans. However, the specific mechanism of zoonotic transmission from dromedaries to humans remains unclear. Despite new efforts and significant advancements in the public health care system, numerous gaps exist in understanding MERS-CoV infections. This chapter summarized the molecular virulence of MERS-CoV, associated immune responses, variations in spike proteins, pathogenesis, and genetic differences in MERS-CoV, SARS-CoV, and SARS-CoV-2. Furthermore, new protocols and active surveillance programs are much needed to evaluate future reoccurrence of MERS-CoV infections and test antiviral agents to develop vaccines that can be useful in treating MERS-CoV.