Cross-species transmission of coronaviruses with a focus on severe acute respiratory syndrome coronavirus 2 infection in animals: a review for the veterinary practitioner.

In 2019 a novel coronavirus termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged from an unidentified source and spread rapidly among humans worldwide. While many human infections are mild, some result in severe clinical disease that in a small proportion of infected people is fatal. The pandemic spread of SARS-CoV-2 has been facilitated by efficient human-to-human transmission of the virus, with no data to indicate that animals contributed to this global health crisis. However, a range of domesticated and wild animals are also susceptible to SARS-CoV-2 infection under both experimental and natural conditions. Humans are presumed to be the source of most animal infections thus far, although natural transmission between mink and between free-ranging deer has occurred, and occasional natural transmission between cats cannot be fully excluded. Considering the ongoing circulation of the virus among people, together with its capacity to evolve through mutation and recombination, the risk of the emergence of animal-adapted variants is not negligible. If such variants remain infectious to humans, this could lead to the establishment of an animal reservoir for the virus, which would complicate control efforts. As such, minimising human-to-animal transmission of SARS-CoV-2 should be considered as part of infection control efforts. The aim of this review is to summarise what is currently known about the species specificity of animal coronaviruses, with an emphasis on SARS-CoV-2, in the broader context of factors that facilitate cross-species transmission of viruses.

Genomic evolution of the human and animal coronavirus diseases.

Different coronaviruses have emerged due to their ability to infect, mutate and recombine multiple species and cell types, suggesting that these viruses will carry on to evolve and origin both veterinary and human diseases. So far, more than fifteen coronavirus-related diseases have been described in animals and seven in humans. Of which recently, a novel human betacoronavirus designated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an emerging zoonotic coronavirus is the causative agent of the coronavirus disease 2019. This virus emerged in China and spread rapidly worldwide. At the end of January 2020, the WHO declared the pandemic as a public health emergency of international concern. In this pandemic, the SARS-CoV-2 virus has infected more than 198 million people, with 4.2 million deaths worldwide (as of 2 August 2021). In the past two decades, this is the third betacoronavirus that has crossed the interspecies barrier from animals to infect humans and other animal species. The diseases caused mainly severe respiratory infections. The aim of this review is to summarize and provide an overview of the coronaviruses that can affect animals and humans and the diseases that ensue, as well as, its genomic relationship.

Comparative Pathogenesis of Bovine and Porcine Respiratory Coronaviruses in the Animal Host Species and SARS-CoV-2 in Humans.

Discovery of bats with severe acute respiratory syndrome (SARS)-related coronaviruses (CoVs) raised the specter of potential future outbreaks of zoonotic SARS-CoV-like disease in humans, which largely went unheeded. Nevertheless, the novel SARS-CoV-2 of bat ancestral origin emerged to infect humans in Wuhan, China, in late 2019 and then became a global pandemic. Less than 5 months after its emergence, millions of people worldwide have been infected asymptomatically or symptomatically and at least 360,000 have died. Coronavirus disease 2019 (COVID-19) in severely affected patients includes atypical pneumonia characterized by a dry cough, persistent fever, and progressive dyspnea and hypoxia, sometimes accompanied by diarrhea and often followed by multiple organ failure, especially of the respiratory and cardiovascular systems. In this minireview, we focus on two endemic respiratory CoV infections of livestock: bovine coronavirus (BCoV) and porcine respiratory coronavirus (PRCV). Both animal respiratory CoVs share some common features with SARS-CoV and SARS-CoV-2. BCoV has a broad host range including wild ruminants and a zoonotic potential. BCoV also has a dual tropism for the respiratory and gastrointestinal tracts. These aspects, their interspecies transmission, and certain factors that impact disease severity in cattle parallel related facets of SARS-CoV or SARS-CoV-2 in humans. PRCV has a tissue tropism for the upper and lower respiratory tracts and a cellular tropism for type 1 and 2 pneumocytes in lung but is generally a mild infection unless complicated by other exacerbating factors, such as bacterial or viral coinfections and immunosuppression (corticosteroids).

Coronaviruses and SARS-COV-2

Coronaviruses (CoVs) cause a broad spectrum of diseases in domestic and wild animals, poultry, and rodents, ranging from mild to severe enteric, respiratory, and systemic disease, and also cause the common cold or pneumonia in humans. Seven coronavirus species are known to cause human infection, 4 of which, HCoV 229E, HCoV NL63, HCoV HKU1 and HCoV OC43, typically cause cold symptoms in immunocompetent individuals. The others namely SARS-CoV (severe acute respiratory syndrome coronavirus), MERS-CoV (Middle East respiratory syndrome coronavirus) were zoonotic in origin and cause severe respiratory illness and fatalities. On 31 December 2019, the existence of patients with pneumonia of an unknown aetiology was reported to WHO by the national authorities in China. This virus was officially identified by the coronavirus study group as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the present outbreak of a coronavirus-associated acute respiratory disease was labelled coronavirus disease 19 (COVID-19). COVID-19's first cases were seen in Turkey on March 10, 2020 and was number 47,029 cases and 1006 deaths after 1 month. Infections with SARS-CoV-2 are now widespread, and as of 10 April 2020, 1,727,602 cases have been confirmed in more than 210 countries, with 105,728 deaths.

Towards a Safer Future: Enhancing Vaccine Development to Combat Animal Coronaviruses.

Coronaviruses (CoVs) are a large class of positively stranded RNA viruses that pose a significant threat to public health, livestock farming, and wild animals. These viruses have the ability to cross species barriers and cause devastating epidemics. Animals are considered to be intermediate hosts for many coronaviruses, and many animal coronaviruses also have the potential for cross-species transmission to humans. Therefore, controlling the epidemic transmission of animal coronaviruses is of great importance to human health. Vaccination programs have proven to be effective in controlling coronaviruses infections, offering a cost-effective approach to reducing morbidity and mortality, so the re-emergence of lethal coronaviruses emphasizes the urgent need for the development of effective vaccines. In this regard, we explore the progress in animal coronavirus vaccine development, covering the latest taxonomy of the main animal coronaviruses, spillover events, diverse vaccine development platforms, potential main targets for animal coronavirus vaccine development, and primary challenges facing animal coronavirus vaccines. We emphasize the urgent need to create a "dual-effect" vaccine capable of eliciting both cellular and humoral immune responses. The goal is to highlight the contributions of veterinary scientists in this field and emphasize the importance of interdisciplinary collaboration between the veterinary and medical communities. By promoting communication and cooperation, we can enhance the development of novel and super vaccines to combat human and animal coronavirus infections in the future.

Development of a universal real-time RT-PCR assay for detection of pan-SARS-coronaviruses with an RNA-based internal control.

The current pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exemplifies the critical need for rapid diagnostic assays to prompt intensified virological monitoring both in human and wild animal populations. To date, there are no clinical validated assays for pan-SARS-coronavirus (pan-SARS-CoV) detection. Here, we suggest an innovative primer design strategy for the diagnosis of pan-SARS-CoVs targeting the envelope (E) gene using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Furthermore, we developed a new primer-probe set targeting human ß2-microglobulin (B2M) as an RNA-based internal control for process efficacy. The universal RT-qPCR assay demonstrated no false-positive amplifications with other human coronaviruses or 20 common respiratory viruses, and its limit of detection (LOD) was 159.16 copies/ml at 95% detection probability. In clinical validation, the assay delivered 100% sensitive results in the detection of SARS-CoV-2-positive oropharyngeal samples (n = 120), including three variants of concern (Wuhan, Delta, and Omicron). Taken together, this universal RT-qPCR assay provides a highly sensitive, robust, and rapid detection of SARS-CoV-1, SARS-CoV-2, and animal-derived SARS-related CoVs.

Evolving ribonucleocapsid assembly/packaging signals in the genomes of the human and animal coronaviruses: targeting, transmission and evolution.

A world-wide COVID-19 pandemic intensified strongly the studies of molecular mechanisms related to the coronaviruses. The origin of coronaviruses and the risks of human-to-human, animal-to-human and human-to-animal transmission of coronaviral infections can be understood only on a broader evolutionary level by detailed comparative studies. In this paper, we studied ribonucleocapsid assembly-packaging signals (RNAPS) in the genomes of all seven known pathogenic human coronaviruses, SARS-CoV, SARS-CoV-2, MERS-CoV, HCoV-OC43, HCoV-HKU1, HCoV-229E and HCoV-NL63 and compared them with RNAPS in the genomes of the related animal coronaviruses including SARS-Bat-CoV, MERS-Camel-CoV, MHV, Bat-CoV MOP1, TGEV and one of camel alphacoronaviruses. RNAPS in the genomes of coronaviruses were evolved due to weakly specific interactions between genomic RNA and N proteins in helical nucleocapsids. Combining transitional genome mapping and Jaccard correlation coefficients allows us to perform the analysis directly in terms of underlying motifs distributed over the genome. In all coronaviruses, RNAPS were distributed quasi-periodically over the genome with the period about 54 nt biased to 57 nt and to 51 nt for the genomes longer and shorter than that of SARS-CoV, respectively. The comparison with the experimentally verified packaging signals for MERS-CoV, MHV and TGEV proved that the distribution of particular motifs is strongly correlated with the packaging signals. We also found that many motifs were highly conserved in both characters and positioning on the genomes throughout the lineages that make them promising therapeutic targets. The mechanisms of encapsidation can affect the recombination and co-infection as well.Communicated by Ramaswamy H. Sarma.

Animal Coronaviruses Induced Apoptosis.

Apoptosis is a form of programmed death that has also been observed in cells infected by several viruses. It is considered one of the most critical innate immune mechanisms that limits pathogen proliferation and propagation before the initiation of the adaptive immune response. Recent studies investigating the cellular responses to SARS-CoV and SARS-CoV-2 infection have revealed that coronaviruses can alter cellular homeostasis and promote cell death, providing evidence that the modulation of apoptotic pathways is important for viral replication and propagation. Despite the genetic diversity among different coronavirus clades and the infection of different cell types and several hosts, research studies in animal coronaviruses indicate that apoptosis in host cells is induced by common molecular mechanisms and apoptotic pathways. We summarize and critically review current knowledge on the molecular aspects of cell-death regulation during animal coronaviruses infection and the viral-host interactions to this process. Future research is expected to lead to a better understanding of the regulation of cell death during coronavirus infection. Moreover, investigating the role of viral proteins in this process will help us to identify novel antiviral targets related to apoptotic signaling pathways.

Animal coronaviruses and SARS-CoV-2.

COVID-19 is a highly contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has rapidly spread to 216 countries and territories since first outbreak in December of 2019, posing a substantial economic losses and extraordinary threats to the public health worldwide. Although bats have been suggested as the natural host of SARS-CoV-2, transmission chains of this virus, role of animals during cross-species transmission, and future concerns remain unclear. Diverse animal coronaviruses have extensively been studied since the discovery of avian coronavirus in 1930s. The current article comprehensively reviews and discusses the current understanding about animal coronaviruses and SARS-CoV-2 for their emergence, transmission, zoonotic potential, alteration of tissue/host tropism, evolution, status of vaccines and surveillance. This study aims at providing guidance for control of COVID-19 and preventative strategies for possible future outbreaks of zoonotic coronavirus via cross-species transmission.

Evolution, Interspecies Transmission, and Zoonotic Significance of Animal Coronaviruses.

Coronaviruses are single-stranded RNA viruses that affect humans and a wide variety of animal species, including livestock, wild animals, birds, and pets. These viruses have an affinity for different tissues, such as those of the respiratory and gastrointestinal tract of most mammals and birds and the hepatic and nervous tissues of rodents and porcine. As coronaviruses target different host cell receptors and show divergence in the sequences and motifs of their structural and accessory proteins, they are classified into groups, which may explain the evolutionary relationship between them. The interspecies transmission, zoonotic potential, and ability to mutate at a higher rate and emerge into variants of concern highlight their importance in the medical and veterinary fields. The contribution of various factors that result in their evolution will provide better insight and may help to understand the complexity of coronaviruses in the face of pandemics. In this review, important aspects of coronaviruses infecting livestock, birds, and pets, in particular, their structure and genome organization having a bearing on evolutionary and zoonotic outcomes, have been discussed.

Cell Entry of Animal Coronaviruses.

Coronaviruses (CoVs) are a group of enveloped positive-sense RNA viruses and can cause deadly diseases in animals and humans. Cell entry is the first and essential step of successful virus infection and can be divided into two ongoing steps: cell binding and membrane fusion. Over the past two decades, stimulated by the global outbreak of SARS-CoV and pandemic of SARS-CoV-2, numerous efforts have been made in the CoV research. As a result, significant progress has been achieved in our understanding of the cell entry process. Here, we review the current knowledge of this essential process, including the viral and host components involved in cell binding and membrane fusion, molecular mechanisms of their interactions, and the sites of virus entry. We highlight the recent findings of host restriction factors that inhibit CoVs entry. This knowledge not only enhances our understanding of the cell entry process, pathogenesis, tissue tropism, host range, and interspecies-transmission of CoVs but also provides a theoretical basis to design effective preventive and therapeutic strategies to control CoVs infection.

Stability of SARS-CoV-2 and other coronaviruses in the environment and on common touch surfaces and the influence of climatic conditions: A review.

Although the unprecedented efforts the world has been taking to control the spread of the human coronavirus disease (COVID-19) and its causative aetiology [severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)], the number of confirmed cases has been increasing drastically. Therefore, there is an urgent need for devising more efficient preventive measures, to limit the spread of the infection until an effective treatment or vaccine is available. The preventive measures depend mainly on the understanding of the transmission routes of this virus, its environmental stability, and its persistence on common touch surfaces. Due to the very limited knowledge about SARS-CoV-2, we can speculate its stability in the light of previous studies conducted on other human and animal coronaviruses. In this review, we present the available data on the stability of coronaviruses (CoVs), including SARS-CoV-2, from previous reports to help understand its environmental survival. According to available data, possible airborne transmission of SARS-CoV-2 has been suggested. SARS-CoV-2 and other human and animal CoVs have remarkably short persistence on copper, latex and surfaces with low porosity as compared to other surfaces like stainless steel, plastics, glass and highly porous fabrics. It has also been reported that SARS-CoV-2 is associated with diarrhoea and that it is shed in the faeces of COVID-19 patients. Some CoVs show persistence in human excrement, sewage and waters for a few days. These findings suggest a possible risk of faecal-oral, foodborne and waterborne transmission of SARS-CoV-2 in developing countries that often use sewage-polluted waters in irrigation and have poor water treatment systems. CoVs survive longer in the environment at lower temperatures and lower relative humidity. It has been suggested that large numbers of COVID-19 cases are associated with cold and dry climates in temperate regions of the world and that seasonality of the virus spread is suspected.

Camelid Inoculation With Middle East Respiratory Syndrome Coronavirus: Experimental Models of Reservoir Host Infection.

Within the past two decades, three zoonotic betacoronaviruses have been associated with outbreaks causing severe respiratory disease in humans. Of these, Middle East respiratory s yndrome coronavirus (MERS-CoV) is the only zoonotic coronavirus that is known to consistently result in frequent zoonotic spillover events from the proximate reservoir host-the dromedary camel. A comprehensive understanding of infection in dromedaries is critical to informing public health recommendations and implementing intervention strategies to mitigate spillover events. Experimental models of reservoir disease are absolutely critical in understanding the pathogenesis and transmission, and are key to testing potential dromedary vaccines against MERS-CoV. In this review, we describe experimental infections of dromedary camels as well as additional camelid models used to further understand the camel's role in MERS-CoV spillover to humans.

Animal coronaviruses and coronavirus disease 2019: Lesson for One Health approach.

Coronaviruses are a group of enveloped, single-stranded, positive-sense RNA viruses that are broadly classified into alpha, beta, gamma, and delta coronavirus genera based on the viral genome. Coronavirus was not thought to be a significant problem in humans until the outbreak of severe acute respiratory syndrome in 2002, but infections in animals, including pigs, cats, dogs, and poultry, have been problematic for a long time. The outbreak of coronavirus disease 2019 in December 2019 in Wuhan, China, drew special attention towards this virus once again. The intermediate host of this novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is yet to be determined, but it has a very close genomic relationship with the bat coronavirus (Bat-CoV), RaTG13 strain, and the pangolin coronaviruses. As veterinary medicine has a long-term experience dealing with coronaviruses, this could be helpful in better understanding and detecting the origin of SARS-CoV-2 and drive human medicine towards the development of vaccines and antiviral drugs through the collaborative and transdisciplinary approaches of One Health.

Drawing Comparisons between SARS-CoV-2 and the Animal Coronaviruses.

The COVID-19 pandemic, caused by a novel zoonotic coronavirus (CoV), SARS-CoV-2, has infected 46,182 million people, resulting in 1,197,026 deaths (as of 1 November 2020), with devastating and far-reaching impacts on economies and societies worldwide. The complex origin, extended human-to-human transmission, pathogenesis, host immune responses, and various clinical presentations of SARS-CoV-2 have presented serious challenges in understanding and combating the pandemic situation. Human CoVs gained attention only after the SARS-CoV outbreak of 2002-2003. On the other hand, animal CoVs have been studied extensively for many decades, providing a plethora of important information on their genetic diversity, transmission, tissue tropism and pathology, host immunity, and therapeutic and prophylactic strategies, some of which have striking resemblance to those seen with SARS-CoV-2. Moreover, the evolution of human CoVs, including SARS-CoV-2, is intermingled with those of animal CoVs. In this comprehensive review, attempts have been made to compare the current knowledge on evolution, transmission, pathogenesis, immunopathology, therapeutics, and prophylaxis of SARS-CoV-2 with those of various animal CoVs. Information on animal CoVs might enhance our understanding of SARS-CoV-2, and accordingly, benefit the development of effective control and prevention strategies against COVID-19.

COVID-19 and pets: When pandemic meets panic.

As the novel coronavirus outbreak spreads globally with devastating effects on human health, pets are also becoming unnecessary victims amidst the pandemic panic. Many have been reluctantly left home alone by owners who have been forced to temporarily evacuate their homes. And, although no evidence exists to indicate that they can either transmit the virus or develop its associated coronavirus disease 2019 (COVID-19), fear among the public that pets might play a role in spreading COVID-19 has resulted in pets being abandoned or even killed. This article outlines some of the ways in which the current pandemic has negatively impacted the welfare of pets. It also highlights the relationships between animal, human, and environmental health, as well as the importance of taking a collaborative transdisciplinary One Health approach to help prevent future COVID-19 outbreaks.

Novel human coronavirus (SARS-CoV-2): A lesson from animal coronaviruses.

The recent pandemic caused by the novel human coronavirus, referrred to as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), not only is having a great impact on the health care systems and economies in all continents but it is also causing radical changes of common habits and life styles. The novel coronavirus (CoV) recognises, with high probability, a zoonotic origin but the role of animals in the SARS-CoV-2 epidemiology is still largely unknown. However, CoVs have been known in animals since several decades, so that veterinary coronavirologists have a great expertise on how to face CoV infections in animals, which could represent a model for SARS-CoV-2 infection in humans. In the present paper, we provide an up-to-date review of the literature currently available on animal CoVs, focusing on the molecular mechanisms that are responsible for the emergence of novel CoV strains with different antigenic, biologic and/or pathogenetic features. A full comprehension of the mechanisms driving the evolution of animal CoVs will help better understand the emergence, spreading, and evolution of SARS-CoV-2.