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Journal ArticleDOI

Coronaviruses in humans and animals: the role of bats in viral evolution.

02 Mar 2021-Environmental Science and Pollution Research (Springer Berlin Heidelberg)-Vol. 28, Iss: 16, pp 19589-19600
TL;DR: Wang et al. as discussed by the authors investigated the role of bats in the emergence of the first serious human coronavirus epidemic (severe acute respiratory syndrome; SARS) and the second one (middle east respiratory syndrome (MERS) in Saudi Arabia (in 2012, 2260 cases, 803 deaths [35.5% of the cases] in 27 countries).
Abstract: Bats act as a natural reservoir for many viruses, including coronaviruses, and have played a crucial epidemiological role in the emergence of many viral diseases. Coronaviruses have been known for 60 years. They are usually responsible for the induction of mild respiratory signs in humans. However, since 2002, the bat-borne virus started to induce fatal epidemics according to WHO reports. In this year, the first serious human coronavirus epidemic (severe acute respiratory syndrome; SARS) occurred (China, 8098 cases, 774 deaths [9.5% of the cases] in 17 countries). The case fatality was higher in elderly patients above 60 years and reached 50% of the cases. SARS epidemic was followed 10 years later by the emergence of the middle east respiratory syndrome (MERS) in Saudi Arabia (in 2012, 2260 cases, 803 deaths [35.5% of the cases] in 27 countries). Finally, in December 2019, a new epidemic in Wuhan, China, (corona virus disease 2019, COVID-19) emerged and could spread to 217 countries infecting more than 86,255,226 cases and killing 1,863,973 people by the end of 2020. There are many reasons why bats are ideal reservoir hosts for viral diseases such as the tolerance of their immune system to the invading viruses for several months. They can actively shed the viruses, although they develop no clinical signs (will be discussed in details later in the review). Bats were directly or indirectly involved in the three previous coronavirus epidemics. The indirect transmission takes place via intermediate hosts including civet cats for SARS and dromedary camels in the case of MERS. Although bats are believed to be the source of COVID-19 pandemic, direct pieces of evidence are still lacking. Therefore, coronaviruses' role in epidemics induction and the epidemiological role of bats are discussed. The current work also presents different evidence (phylogenetic data, animal experiments, bats artificial infection studies, and computerized models of SARS-CoV2 evolution) that underline the involvement of bats in the epidemiology of the pandemic.

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Citations
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Journal ArticleDOI
TL;DR: In this article, the therapeutic efficacy of Ivermectin mucoadhesive nanosuspension intranasal spray in treatment of patients with mild COVID-19 was evaluated.
Abstract: Background Ivermectin is an FDA-approved broad-spectrum anti-parasitic agent that has been shown to inhibit SARS-CoV-2 replication in vitro. Objective We aimed to assess the therapeutic efficacy of ivermectin mucoadhesive nanosuspension intranasal spray in treatment of patients with mild COVID-19. Methods This clinical trial included 114 patients diagnosed as mild COVID-19. Patients were divided randomly into two age and sex-matched groups; group A comprising 57 patients received ivermectin nanosuspension nasal spray twice daily plus the Egyptian protocol of treatment for mild COVID-19 and group B comprising 57 patients received the Egyptian protocol for mild COVID-19 only. Evaluation of the patients was performed depending on improvement of presenting manifestations, negativity of two consecutive pharyngeal swabs for the COVID-19 nucleic acid via rRT-PCR and assessments of hematological and biochemical parameters in the form of complete blood counts, C-reactive protein, serum ferritin and d-dimer which were performed at presentation and 7 days later. Results Of the included patients confirmed with mild COVID-19, 82 were males (71.9%) and 32 females (28.1%) with mean age 45.1 ± 18.9. In group A, 54 patients (94.7%) achieved 2 consecutive negative PCR nasopharyngeal swabs in comparison to 43 patients (75.4%) in group B with P = 0.004. The durations of fever, cough, dyspnea and anosmia were significantly shorter in group A than group B, without significant difference regarding the duration of gastrointestinal symptoms. Duration taken for nasopharyngeal swab to be negative was significantly shorter in group A than in group B (8.3± 2.8 days versus 12.9 ± 4.3 days; P = 0.0001). Conclusion Local use of ivermectin mucoadhesive nanosuspension nasal spray is safe and effective in treatment of patients with mild COVID-19 with rapid viral clearance and shortening the anosmia duration. Clinicaltrialsgov identifier NCT04716569; https://clinicaltrials.gov/ct2/show/NCT04716569.

28 citations

Journal ArticleDOI
TL;DR: In this article, the authors describe the main investigations leading to the discovery of RDV and its subsequent development as an antiviral agent, focusing on the main clinical trials investigating its efficacy in terms of symptom resolution and mortality reduction.
Abstract: Introduction Remdesivir (RDV) is an inhibitor of the viral RNA-dependent RNA polymerases that are active in some RNA viruses, including the Ebola virus and zoonotic coronaviruses. When severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) was identified as the etiologic agent of the coronavirus disease 2019 (COVID-19), several investigations have assessed the potential activity of RDV in inhibiting viral replication, giving rise to hope for an effective treatment. Areas covered In this review, the authors describe the main investigations leading to the discovery of RDV and its subsequent development as an antiviral agent, focusing on the main clinical trials investigating its efficacy in terms of symptom resolution and mortality reduction. Expert opinion RDV is the most widely investigated antiviral drug for the treatment of COVID-19. This attention on RDV activity against SARS-CoV-2 is justified by promising in vitro studies, which demonstrated that RDV was able to suppress viral replication without significant toxicity. Such activity was confirmed by an investigation in an animal model and by the results of preliminary clinical investigations. Nevertheless, the efficacy of RDV in reducing mortality has not been clearly demonstrated.

17 citations

Posted ContentDOI
TL;DR: The founding of SARS-CoV-2 in wild animal reservoirs can confronts the control of the virus in humans and might carry a risk to the welfare and conservation of wildlife as well, so it is suggested vaccinating pet, and captive animals to stop spillover and spillback events.
Abstract: The exact origin of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and source of introduction into humans has not been established yet, though it might be originated from animals. Therefore, we conducted a study to understand the putative reservoirs, transmission dynamics, and susceptibility patterns of SARS-CoV-2 in animals. Rhinolophus bats are presumed to be natural progenitors of SARS-CoV-2-related viruses. Initially, pangolin was thought to be the source of spillover to humans, but they might be infected by human or other animal species. So, the virus spillover pathways to humans remain unknown. Human-to-animal transmission has been testified in pet, farmed, zoo and free-ranging wild animals. Infected animals can transmit the virus to other animals in natural settings like mink-to-mink and mink-to-cat transmission. Animal-to-human transmission is not a persistent pathway, while mink-to-human transmission continues to be illuminated. Multiple companions and captive wild animals were infected by an emerging alpha variant of concern (B.1.1.7 lineage) whereas Asiatic lions were infected by delta variant, (B.1.617.2). To date, multiple animal species - cat, ferrets, non-human primates, hamsters and bats - showed high susceptibility to SARS-CoV-2 in the experimental condition, while swine, poultry, cattle showed no susceptibility. The founding of SARS-CoV-2 in wild animal reservoirs can confront the control of the virus in humans and might carry a risk to the welfare and conservation of wildlife as well. We suggest vaccinating pets and captive animals to stop spillovers and spillback events. We recommend sustainable One Health surveillance at the animal-human-environmental interface to detect and prevent future epidemics and pandemics by Disease X.

14 citations

Journal ArticleDOI
TL;DR: In this article, the authors summarized a few examples of human viral infections for which the use of bovines has contributed to the acquisition of new knowledge to improve human health against viral infections covering the convergence between some human and bovine viruses and using Bovines as disease models.
Abstract: In the last 40 years, novel viruses have evolved at a much faster pace than other pathogens. Viral diseases pose a significant threat to public health around the world. Bovines have a longstanding history of significant contributions to human nutrition, agricultural, industrial purposes, medical research, drug and vaccine development, and livelihood. The life cycle, genomic structures, viral proteins, and pathophysiology of bovine viruses studied in vitro paved the way for understanding the human counterparts. Calf model has been used for testing vaccines against RSV, papillomavirus vaccines and anti-HCV agents were principally developed after using the BPV and BVDV model, respectively. Some bovine viruses-based vaccines (BPIV-3 and bovine rotaviruses) were successfully developed, clinically tried, and commercially produced. Cows, immunized with HIV envelope glycoprotein, produced effective broadly neutralizing antibodies in their serum and colostrum against HIV. Here, we have summarized a few examples of human viral infections for which the use of bovines has contributed to the acquisition of new knowledge to improve human health against viral infections covering the convergence between some human and bovine viruses and using bovines as disease models. Additionally, the production of vaccines and drugs, bovine-based products were covered, and the precautions in dealing with bovines and bovine-based materials.

13 citations

Journal ArticleDOI
TL;DR: The exact origin of SARS-CoV-2 and source of introduction into humans has not been established yet, though it might be originated from animals as discussed by the authors , and therefore, the virus spillover pathways to humans remain unknown.
Abstract: The exact origin of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and source of introduction into humans has not been established yet, though it might be originated from animals. Therefore, we conducted a study to understand the putative reservoirs, transmission dynamics, and susceptibility patterns of SARS-CoV-2 in animals. Rhinolophus bats are presumed to be natural progenitors of SARS-CoV-2-related viruses. Initially, pangolin was thought to be the source of spillover to humans, but they might be infected by human or other animal species. So, the virus spillover pathways to humans remain unknown. Human-to-animal transmission has been testified in pet, farmed, zoo and free-ranging wild animals. Infected animals can transmit the virus to other animals in natural settings like mink-to-mink and mink-to-cat transmission. Animal-to-human transmission is not a persistent pathway, while mink-to-human transmission continues to be illuminated. Multiple companions and captive wild animals were infected by an emerging alpha variant of concern (B.1.1.7 lineage) whereas Asiatic lions were infected by delta variant, (B.1.617.2). To date, multiple animal species - cat, ferrets, non-human primates, hamsters and bats - showed high susceptibility to SARS-CoV-2 in the experimental condition, while swine, poultry, cattle showed no susceptibility. The founding of SARS-CoV-2 in wild animal reservoirs can confront the control of the virus in humans and might carry a risk to the welfare and conservation of wildlife as well. We suggest vaccinating pets and captive animals to stop spillovers and spillback events. We recommend sustainable One Health surveillance at the animal-human-environmental interface to detect and prevent future epidemics and pandemics by Disease X.

13 citations

References
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Journal ArticleDOI
27 Nov 2003-Nature
TL;DR: It is found that a soluble form of ACE2, but not of the related enzyme ACE1, blocked association of the S1 domain with Vero E6 cells, indicating that ACE2 is a functional receptor for SARS-CoV.
Abstract: Spike (S) proteins of coronaviruses, including the coronavirus that causes severe acute respiratory syndrome (SARS), associate with cellular receptors to mediate infection of their target cells Here we identify a metallopeptidase, angiotensin-converting enzyme 2 (ACE2), isolated from SARS coronavirus (SARS-CoV)-permissive Vero E6 cells, that efficiently binds the S1 domain of the SARS-CoV S protein We found that a soluble form of ACE2, but not of the related enzyme ACE1, blocked association of the S1 domain with Vero E6 cells 293T cells transfected with ACE2, but not those transfected with human immunodeficiency virus-1 receptors, formed multinucleated syncytia with cells expressing S protein Furthermore, SARS-CoV replicated efficiently on ACE2-transfected but not mock-transfected 293T cells Finally, anti-ACE2 but not anti-ACE1 antibody blocked viral replication on Vero E6 cells Together our data indicate that ACE2 is a functional receptor for SARS-CoV

5,149 citations

Journal ArticleDOI
TL;DR: The clinical picture was remarkably similar to that of the severe acute respiratory syndrome (SARS) outbreak in 2003 and reminds us that animal coronaviruses can cause severe disease in humans.
Abstract: A previously unknown coronavirus was isolated from the sputum of a 60-year-old man who presented with acute pneumonia and subsequent renal failure with a fatal outcome in Saudi Arabia. The virus (called HCoV-EMC) replicated readily in cell culture, producing cytopathic effects of rounding, detachment, and syncytium formation. The virus represents a novel betacoronavirus species. The closest known relatives are bat coronaviruses HKU4 and HKU5. Here, the clinical data, virus isolation, and molecular identification are presented. The clinical picture was remarkably similar to that of the severe acute respiratory syndrome (SARS) outbreak in 2003 and reminds us that animal coronaviruses can cause severe disease in humans.

4,809 citations

Journal ArticleDOI
TL;DR: The viral factors that enabled the emergence of diseases such as severe acute respiratory syndrome and Middle East respiratory syndrome are explored and the diversity and potential of bat-borne coronaviruses are highlighted.
Abstract: Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are two highly transmissible and pathogenic viruses that emerged in humans at the beginning of the 21st century. Both viruses likely originated in bats, and genetically diverse coronaviruses that are related to SARS-CoV and MERS-CoV were discovered in bats worldwide. In this Review, we summarize the current knowledge on the origin and evolution of these two pathogenic coronaviruses and discuss their receptor usage; we also highlight the diversity and potential of spillover of bat-borne coronaviruses, as evidenced by the recent spillover of swine acute diarrhoea syndrome coronavirus (SADS-CoV) to pigs. Coronaviruses have a broad host range and distribution, and some highly pathogenic lineages have spilled over to humans and animals. Here, Cui, Li and Shi explore the viral factors that enabled the emergence of diseases such as severe acute respiratory syndrome and Middle East respiratory syndrome.

3,970 citations

Book ChapterDOI
TL;DR: A brief introduction to coronaviruses is provided discussing their replication and pathogenicity, and current prevention and treatment strategies, and the outbreaks of the highly pathogenic Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and the recently identified Middle Eastern Respiratories Syndrome Cor onavirus
Abstract: Coronaviruses (CoVs), enveloped positive-sense RNA viruses, are characterized by club-like spikes that project from their surface, an unusually large RNA genome, and a unique replication strategy. Coronaviruses cause a variety of diseases in mammals and birds ranging from enteritis in cows and pigs and upper respiratory disease in chickens to potentially lethal human respiratory infections. Here we provide a brief introduction to coronaviruses discussing their replication and pathogenicity, and current prevention and treatment strategies. We also discuss the outbreaks of the highly pathogenic Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and the recently identified Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV).

2,846 citations

Journal ArticleDOI
TL;DR: Tremendous progress has been made in understanding the molecular basis of the antiviral actions of interferons (IFNs), as well as strategies evolved by viruses to antagonize the actions of IFNs.
Abstract: Tremendous progress has been made in understanding the molecular basis of the antiviral actions of interferons (IFNs), as well as strategies evolved by viruses to antagonize the actions of IFNs. Furthermore, advances made while elucidating the IFN system have contributed significantly to our understanding in multiple areas of virology and molecular cell biology, ranging from pathways of signal transduction to the biochemical mechanisms of transcriptional and translational control to the molecular basis of viral pathogenesis. IFNs are approved therapeutics and have moved from the basic research laboratory to the clinic. Among the IFN-induced proteins important in the antiviral actions of IFNs are the RNA-dependent protein kinase (PKR), the 2',5'-oligoadenylate synthetase (OAS) and RNase L, and the Mx protein GTPases. Double-stranded RNA plays a central role in modulating protein phosphorylation and RNA degradation catalyzed by the IFN-inducible PKR kinase and the 2'-5'-oligoadenylate-dependent RNase L, respectively, and also in RNA editing by the IFN-inducible RNA-specific adenosine deaminase (ADAR1). IFN also induces a form of inducible nitric oxide synthase (iNOS2) and the major histocompatibility complex class I and II proteins, all of which play important roles in immune response to infections. Several additional genes whose expression profiles are altered in response to IFN treatment and virus infection have been identified by microarray analyses. The availability of cDNA and genomic clones for many of the components of the IFN system, including IFN-alpha, IFN-beta, and IFN-gamma, their receptors, Jak and Stat and IRF signal transduction components, and proteins such as PKR, 2',5'-OAS, Mx, and ADAR, whose expression is regulated by IFNs, has permitted the generation of mutant proteins, cells that overexpress different forms of the proteins, and animals in which their expression has been disrupted by targeted gene disruption. The use of these IFN system reagents, both in cell culture and in whole animals, continues to provide important contributions to our understanding of the virus-host interaction and cellular antiviral response.

2,621 citations