Newly Emerging Human Coronaviruses: Animal Models and Vaccine Research for SARS, MERS, and COVID-19.
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ABSTRACT:
SUBMITTER: Lee P
PROVIDER: S-EPMC7458800 | biostudies-literature | 2020 Aug
REPOSITORIES: biostudies-literature
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Project description:Two novel coronaviruses have emerged to cause severe disease in humans. While bats may be the primary reservoir for both viruses, SARS coronavirus (SARS-CoV) likely crossed into humans from civets in China, and MERS coronavirus (MERS-CoV) has been transmitted from camels in the Middle East. Unlike SARS-CoV that resolved within a year, continued introductions of MERS-CoV present an on-going public health threat. Animal models are needed to evaluate countermeasures against emerging viruses. With SARS-CoV, several animal species were permissive to infection. In contrast, most laboratory animals are refractory or only semi-permissive to infection with MERS-CoV. This host-range restriction is largely determined by sequence heterogeneity in the MERS-CoV receptor. We describe animal models developed to study coronaviruses, with a focus on host-range restriction at the level of the viral receptor and discuss approaches to consider in developing a model to evaluate countermeasures against MERS-CoV.
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Project description:The first major pandemic of the new millennium that arose from southern China in 2002 was of zoonotic origin from wild game animals, called severe acute respiratory syndrome [SARS]. The culprit was determined to be a coronavirus of animal origin [SARS-CoV]. The discovery of the SARS-CoV, which caused an outbreak of >8000 people in >30 countries with fatality of about 10%, resulted in intense search for novel coronaviruses with potentially high pathogenicity. Ten years later after the SARS pandemic, another novel coronavirus crossed the species barrier from bats to humans through an intermediate camel host, to produce a severe lower respiratory infection labeled the Middle East respiratory syndrome [MERS]. A novel coronavirus [MERS-CoV] was first identified in September 2012, from patients who resided or traveled to Saudi Arabia. The MERS-CoV spread through contacts with camel and subsequently from human to human via droplet transmission. MERS cases occurred in several other countries including in Europe and the United States, mainly from residence or travel to the Arabian Peninsula, but was not of pandemic potential. However, in the spring of 2015, a MERS outbreak started in South Korea which was initiated by a returning traveler from Saudi Arabia, and subsequently secondary infection of over 186 local residents occurred. Recent estimate in May 2015 indicates that the MERS-CoV have afflicted 1167 patients with MERS worldwide with 479 deaths [41% fatality]. Thus MERS is more deadly than SARS but appears to be less contagious. However, unlike SARS which has not reappeared since 2002–2003, MERS-CoV have the potential to cause sporadic or local outbreaks for many years as the virus may now be entrenched endemically in dromedary camels of the Middle East.
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Project description:This article introduces a series of invited papers in Antiviral Research marking the 10th anniversary of the outbreak of severe acute respiratory syndrome (SARS), caused by a novel coronavirus that emerged in southern China in late 2002. Until that time, coronaviruses had not been recognized as agents causing severe disease in humans, hence, the emergence of the SARS-CoV came as a complete surprise. Research during the past ten years has revealed the existence of a diverse pool of coronaviruses circulating among various bat species and other animals, suggesting that further introductions of highly pathogenic coronaviruses into the human population are not merely probable, but inevitable. The recent emergence of another coronavirus causing severe disease, Middle East respiratory syndrome (MERS), in humans, has made it clear that coronaviruses pose a major threat to human health, and that more research is urgently needed to elucidate their replication mechanisms, identify potential drug targets, and develop effective countermeasures. In this series, experts in many different aspects of coronavirus replication and disease will provide authoritative, up-to-date reviews of the following topics: - clinical management and infection control of SARS; - reservoir hosts of coronaviruses; - receptor recognition and cross-species transmission of SARS-CoV; - SARS-CoV evasion of innate immune responses; - structures and functions of individual coronaviral proteins; - anti-coronavirus drug discovery and development; and - the public health legacy of the SARS outbreak. Each article will be identified in the last line of its abstract as belonging to the series "From SARS to MERS: 10years of research on highly pathogenic human coronaviruses."
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Project description:The coronavirus disease 2019 (COVID-19) pandemic has spread around the globe very rapidly. Previously, the evolution pattern and similarity among the COVID-19 causative organism severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and causative organisms of other similar infections have been determined using a single type of genetic marker in different studies. Herein, the SARS-CoV-2 and related β coronaviruses Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV, bat coronavirus (BAT-CoV) were comprehensively analyzed using a custom-built pipeline that employed phylogenetic approaches based on multiple types of genetic markers including the whole genome sequences, mutations in nucleotide sequences, mutations in protein sequences, and microsatellites. The whole-genome sequence-based phylogeny revealed that the strains of SARS-CoV-2 are more similar to the BAT-CoV strains. The mutational analysis showed that on average MERS-CoV and BAT-CoV genomes differed at 134.21 and 136.72 sites, respectively, whereas the SARS-CoV genome differed at 26.64 sites from the reference genome of SARS-CoV-2. Furthermore, the microsatellite analysis highlighted a relatively higher number of average microsatellites for MERS-CoV and SARS-CoV-2 (106.8 and 107, respectively), and a lower number for SARS-CoV and BAT-CoV (95.8 and 98.5, respectively). Collectively, the analysis of multiple genetic markers of selected β viral genomes revealed that the newly born SARS-COV-2 is closely related to BAT-CoV, whereas, MERS-CoV is more distinct from the SARS-CoV-2 than BAT-CoV and SARS-CoV.
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Project description:Salmonellosis remains an important cause of human disease worldwide. While there are several licensed vaccines for Salmonella enterica serovar Typhi, these vaccines are generally ineffective against other Salmonella serovars. Vaccines that target paratyphoid and nontyphoidal Salmonella serovars are very much in need. Preclinical evaluation of candidate vaccines is highly dependent on the availability of appropriate scientific tools, particularly animal models. Many different animal models exist for various Salmonella serovars, from whole-animal models to smaller models, such as those recently established in insects. Here, we discuss various mouse, rat, rabbit, calf, primate, and insect models for Salmonella infection, all of which have their place in research. However, choosing the right model is imperative in selecting the best vaccine candidates for further clinical testing. In this minireview, we summarize the various animal models that are used to assess salmonellosis, highlight some of the advantages and disadvantages of each, and discuss their value in vaccine development.
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Project description:Viruses are having great time as they seem to have bogged humans down. Severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and novel coronavirus (COVID-19) are the three major coronaviruses of present-day global human and animal health concern. COVID-19 caused by SARS-CoV-2 is identified as the newest disease, presumably of bat origin. Different theories on the evolution of viruses are in circulation, yet there is no denying the fact that the animal source is the skeleton. The whole world is witnessing the terror of the COVID-19 pandemic that is following the same path of SARS and MERS, and seems to be more severe. In addition to humans, several species of animals are reported to have been infected with these life-threatening viruses. The possible routes of transmission and their zoonotic potentialities are the subjects of intense research. This review article aims to overview the link of all these three deadly coronaviruses among animals along with their phylogenic evolution and cross-species transmission. This is essential since animals as pets or food are said to pose some risk, and their better understanding is a must in order to prepare a possible plan for future havoc in both human and animal health. Although COVID-19 is causing a human health hazard globally, its reporting in animals are limited compared to SARS and MERS. Non-human primates and carnivores are most susceptible to SARS-coronavirus and SARS-CoV-2, respectively, whereas the dromedary camel is susceptible to MERS-coronavirus. Phylogenetically, the trio viruses are reported to have originated from bats and have special capacity to undergo mutation and genomic recombination in order to infect humans through its reservoir or replication host. However, it is difficult to analyze how the genomic pattern of coronaviruses occurs. Thus, increased possibility of new virus-variants infecting humans and animals in the upcoming days seems to be the biggest challenge for the future of the world. One health approach is portrayed as our best way ahead, and understanding the animal dimension will go a long way in formulating such preparedness plans.
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Project description:Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a new type of coronavirus that causes the Coronavirus Disease 2019 (COVID-19), which has been the most challenging pandemic in this century. Considering its high mortality and rapid spread, an effective vaccine is urgently needed to control this pandemic. As a result, the academia, industry, and government sectors are working tightly together to develop and test a variety of vaccines at an unprecedented pace. In this review, we outline the essential coronavirus biological characteristics that are important for vaccine design. In addition, we summarize key takeaways from previous vaccination studies of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV), highlighting the pros and cons of each immunization strategy. Finally, based on these prior vaccination experiences, we discuss recent progress and potential challenges of COVID-19 vaccine development.
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Project description:Coronaviruses (CoVs) cause diseases such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease 2019 (COVID-19). Therefore, this study was conducted to combat major CoVs via a trivalent subunit vaccine, which was engineered by implementing sequences of spike (S) protein, nucleocapsid (N), envelope (E), membrane (M) protein, non-structural protein (nsp) 3, and nsp8 antigens. The CTL, HTL, MHC I, and IFN-γ epitopes were predicted via CTLPRED, IEDB, and IFN epitope servers, respectively. Also, to stimulate strong helper T lymphocytes (HTLs) responses, Pan HLA DR-binding epitope (PADRE) was used. Also, for boosting the immune response, β-defensin 2 was added to the construct as an adjuvant. Furthermore, TAT was applied to the vaccine to facilitate the intracellular delivery. Finally, TAT, adjuvant, PADRE, and selected epitopes were appropriately assembled. Based on the predicted epitopes, a trivalent multi-epitope vaccine with a molecular weight of 74.8 kDa was constructed. Further analyses predicted the molecule to be a strong antigen, and a non-allergenic and soluble protein. Secondary and tertiary structures were predicted. Additionally, analyses validated the stability of the proposed vaccine. Molecular docking and molecular dynamics simulation (MDS) showed binding affinity and stability of the vaccine-TLR3 complex was favorable. The predicted epitopes demonstrated a strong potential to stimulate T and B-cell mediated immune responses. Furthermore, codon optimization and in silico cloning guaranteed increased expression. In summary, investigations demonstrated that this next-generation approach might provide a new horizon for the development of a highly immunogenic vaccine against SARS-CoV, MERS-CoV, and SARS-CoV-2.Communicated by Ramaswamy H. Sarma.
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Project description:Emerging and re-emerging viral diseases can create devastating effects on human lives and may also lead to economic crises. The ongoing COVID-19 pandemic due to the novel coronavirus (nCoV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which originated in Wuhan, China, has caused a global public health emergency. To date, the molecular mechanism of transmission of SARS-CoV-2, its clinical manifestations and pathogenesis is not completely understood. The global scientific community has intensified its efforts in understanding the biology of SARS-CoV-2 for development of vaccines and therapeutic interventions to prevent the rapid spread of the virus and to control mortality and morbidity associated with COVID-19. To understand the pathophysiology of SARS-CoV-2, appropriate animal models that mimic the biology of human SARS-CoV-2 infection are urgently needed. In this review, we outline animal models that have been used to study previous human coronaviruses (HCoVs), including severe acute respiratory syndrome coronavirus (SARS-CoV) and middle east respiratory syndrome coronavirus (MERS-CoV). Importantly, we discuss models that are appropriate for SARS-CoV-2 as well as the advantages and disadvantages of various available methods.
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