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1.
Comput Biol Chem ; 96: 107613, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1549716

ABSTRACT

Coronavirus Disease 2019 (COVID-19) is an ongoing global health emergency that has caused tremendous stress and loss of life worldwide. The viral spike glycoprotein is a critical molecule mediating transmission of SARS-CoV-2 by interacting with human ACE2. However, through the course of the pandemics, there has not been a thorough analysis of the spike protein mutations, and on how these mutants influence the transmission of SARS-CoV-2. Besides, cases of SARS-CoV-2 infection among pets and wild animals have been reported, so the susceptibility of these animals requires great attention to investigate, as they may also link to the renewed question of a possible intermediate host for SARS-CoV-2 before it was transmitted to humans. With over 226,000 SARS-CoV-2 sequences obtained, we found 1573 missense mutations in the spike gene, and 226 of them were within the receptor-binding domain (RBD) region that directly interacts with human ACE2. Modeling the interactions between SARS-CoV-2 spike mutants and ACE2 molecules showed that most of the 74 missense mutations in the RBD region of the interaction interface had little impact on spike binding to ACE2, whereas several within the spike RBD increased the binding affinity toward human ACE2 thus making the virus likely more contagious. On the other hand, modeling the interactions between animal ACE2 molecules and SARS-CoV-2 spike revealed that many pets and wild animals' ACE2 had a variable binding ability. Particularly, ACE2 of bamboo rat had stronger binding to SARS-CoV-2 spike protein, whereas that of mole, vole, Mus pahari, palm civet, and pangolin had a weaker binding compared to human ACE2. Our results provide structural insights into the impact on interactions of the SARS-CoV-2 spike mutants to human ACE2, and shed light on SARS-CoV-2 transmission in pets and wild animals, and possible clues to the intermediate host(s) for SARS-CoV-2.


Subject(s)
Angiotensin-Converting Enzyme 2/chemistry , COVID-19/veterinary , COVID-19/virology , Mutation, Missense , SARS-CoV-2/chemistry , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Angiotensin-Converting Enzyme 2/genetics , Animals , Animals, Wild/genetics , Animals, Wild/virology , COVID-19/transmission , Computational Biology , Host Microbial Interactions/genetics , Host Specificity/genetics , Humans , Molecular Dynamics Simulation , Pandemics/veterinary , Peptidyl-Dipeptidase A/chemistry , Peptidyl-Dipeptidase A/genetics , Pets/genetics , Pets/virology , Protein Interaction Domains and Motifs/genetics , Risk Factors
2.
Viruses ; 13(11)2021 11 15.
Article in English | MEDLINE | ID: covidwho-1538547

ABSTRACT

2014 marked the first emergence of avian influenza A(H5N8) in Jeonbuk Province, South Korea, which then quickly spread worldwide. In the midst of the 2020-2021 H5N8 outbreak, it spread to domestic poultry and wild waterfowl shorebirds, leading to the first human infection in Astrakhan Oblast, Russia. Despite being clinically asymptomatic and without direct human-to-human transmission, the World Health Organization stressed the need for continued risk assessment given the nature of Influenza to reassort and generate novel strains. Given its promiscuity and easy cross to humans, the urgency to understand the mechanisms of possible species jumping to avert disastrous pandemics is increasing. Addressing the epidemiology of H5N8, its mechanisms of species jumping and its implications, mutational and reassortment libraries can potentially be built, allowing them to be tested on various models complemented with deep-sequencing and automation. With knowledge on mutational patterns, cellular pathways, drug resistance mechanisms and effects of host proteins, we can be better prepared against H5N8 and other influenza A viruses.


Subject(s)
Influenza A Virus, H5N8 Subtype/genetics , Influenza in Birds/virology , Poultry Diseases/virology , Animals , Birds/virology , Humans , Influenza in Birds/epidemiology , Pandemics/veterinary , Phylogeny , Poultry/virology , Poultry Diseases/epidemiology , Republic of Korea/epidemiology , Russia/epidemiology
3.
MMWR Morb Mortal Wkly Rep ; 69(23): 710-713, 2020 Jun 12.
Article in English | MEDLINE | ID: covidwho-1389844

ABSTRACT

On April 22, CDC and the U.S. Department of Agriculture (USDA) reported cases of two domestic cats with confirmed infection with SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). These are the first reported companion animals (including pets and service animals) with SARS-CoV-2 infection in the United States, and among the first findings of SARS-CoV-2 symptomatic companion animals reported worldwide. These feline cases originated from separate households and were epidemiologically linked to suspected or confirmed human COVID-19 cases in their respective households. Notification of presumptive positive animal test results triggered a One Health* investigation by state and federal partners, who determined that no further transmission events to other animals or persons had occurred. Both cats fully recovered. Although there is currently no evidence that animals play a substantial role in spreading COVID-19, CDC advises persons with suspected or confirmed COVID-19 to restrict contact with animals during their illness and to monitor any animals with confirmed SARS-CoV-2 infection and separate them from other persons and animals at home (1).


Subject(s)
Betacoronavirus/isolation & purification , Cat Diseases/diagnosis , Cat Diseases/virology , Coronavirus Infections/diagnosis , Coronavirus Infections/veterinary , Pandemics/veterinary , Pets/virology , Pneumonia, Viral/diagnosis , Pneumonia, Viral/veterinary , Animals , COVID-19 , Cats , Coronavirus Infections/transmission , Female , Humans , Male , New York , Pneumonia, Viral/transmission , SARS-CoV-2 , Zoonoses
5.
Euro Surveill ; 26(5)2021 02.
Article in English | MEDLINE | ID: covidwho-1067624

ABSTRACT

In June-November 2020, SARS-CoV-2-infected mink were detected in 290 of 1,147 Danish mink farms. In North Denmark Region, 30% (324/1,092) of people found connected to mink farms tested SARS-CoV-2-PCR-positive and approximately 27% (95% confidence interval (CI): 25-30) of SARS-CoV-2-strains from humans in the community were mink-associated. Measures proved insufficient to mitigate spread. On 4 November, the government ordered culling of all Danish mink. Farmed mink constitute a potential virus reservoir challenging pandemic control.


Subject(s)
Animals, Wild/virology , COVID-19/epidemiology , COVID-19/veterinary , Disease Outbreaks/veterinary , Disease Reservoirs/veterinary , Disease Transmission, Infectious/veterinary , Mink/virology , Pandemics/veterinary , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Viral Zoonoses/transmission , Animals , COVID-19/transmission , COVID-19/virology , COVID-19 Nucleic Acid Testing , Denmark/epidemiology , Disease Outbreaks/statistics & numerical data , Disease Reservoirs/virology , Farms , Genes, Viral , Humans , Incidence , Polymerase Chain Reaction , Public Health , RNA, Viral/analysis , RNA, Viral/genetics , SARS-CoV-2/classification , Viral Zoonoses/virology , Whole Genome Sequencing , Zoonoses/transmission , Zoonoses/virology
7.
Vet Q ; 40(1): 322-330, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-900144

ABSTRACT

Feline infectious peritonitis (FIP) is a viral-induced, immune-mediated disease of cats caused by virulent biotypes of feline coronaviruses (FCoV), known as the feline infectious peritonitis virus (FIPV). Historically, three major pharmacological approaches have been employed to treat FIP: (1) immunomodulators to stimulate the patient's immune system non-specifically to reduce the clinical effects of the virus through a robust immune response, (2) immunosuppressive agents to dampen clinical signs temporarily, and (3) re-purposed human antiviral drugs, all of which have been unsuccessful to date in providing reliable efficacious treatment options for FIPV. Recently, antiviral studies investigating the broad-spectrum coronavirus protease inhibitor, GC376, and the adenosine nucleoside analogue GS-441524, have resulted in increased survival rates and clinical cure in many patients. However, prescriber access to these antiviral therapies is currently problematic as they have not yet obtained registration for veterinary use. Consequently, FIP remains challenging to treat. The purpose of this review is to provide an update on the current status of therapeutics for FIP. Additionally, due to interest in coronaviruses resulting from the current human pandemic, this review provides information on domesticated cats identified as SARS-CoV-2 positive.


Subject(s)
Antiviral Agents/therapeutic use , Betacoronavirus , Coronavirus Infections/veterinary , Feline Infectious Peritonitis/drug therapy , Immunologic Factors/therapeutic use , Pandemics/veterinary , Pneumonia, Viral/veterinary , Animals , COVID-19 , Cats , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , SARS-CoV-2
8.
Commun Biol ; 3(1): 641, 2020 10 27.
Article in English | MEDLINE | ID: covidwho-894423

ABSTRACT

The emergence of SARS-CoV-2 has caused over a million human deaths and massive global disruption. The viral infection may also represent a threat to our closest living relatives, nonhuman primates. The contact surface of the host cell receptor, ACE2, displays amino acid residues that are critical for virus recognition, and variations at these critical residues modulate infection susceptibility. Infection studies have shown that some primate species develop COVID-19-like symptoms; however, the susceptibility of most primates is unknown. Here, we show that all apes and African and Asian monkeys (catarrhines), exhibit the same set of twelve key amino acid residues as human ACE2. Monkeys in the Americas, and some tarsiers, lemurs and lorisoids, differ at critical contact residues, and protein modeling predicts that these differences should greatly reduce SARS-CoV-2 binding affinity. Other lemurs are predicted to be closer to catarrhines in their susceptibility. Our study suggests that apes and African and Asian monkeys, and some lemurs, are likely to be highly susceptible to SARS-CoV-2. Urgent actions have been undertaken to limit the exposure of great apes to humans, and similar efforts may be necessary for many other primate species.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/veterinary , Host Specificity/genetics , Pandemics/veterinary , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/veterinary , Primate Diseases/enzymology , Primates/genetics , Receptors, Virus/genetics , Amino Acid Sequence , Amino Acid Substitution , Angiotensin-Converting Enzyme 2 , Animals , Betacoronavirus/physiology , Biological Evolution , COVID-19 , Chiroptera/genetics , Conserved Sequence , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Genetic Predisposition to Disease , Mammals/genetics , Models, Molecular , Mutation, Missense , Peptidyl-Dipeptidase A/chemistry , Phylogeny , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Point Mutation , Primate Diseases/virology , Protein Binding , Protein Conformation , Risk , SARS-CoV-2 , Sequence Alignment , Sequence Homology, Amino Acid , Species Specificity , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism
9.
mBio ; 11(5)2020 10 13.
Article in English | MEDLINE | ID: covidwho-868276

ABSTRACT

Despite numerous barriers to transmission, zoonoses are the major cause of emerging infectious diseases in humans. Among these, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and ebolaviruses have killed thousands; the human immunodeficiency virus (HIV) has killed millions. Zoonoses and human-to-animal cross-species transmission are driven by human actions and have important management, conservation, and public health implications. The current SARS-CoV-2 pandemic, which presumably originated from an animal reservoir, has killed more than half a million people around the world and cases continue to rise. In March 2020, New York City was a global epicenter for SARS-CoV-2 infections. During this time, four tigers and three lions at the Bronx Zoo, NY, developed mild, abnormal respiratory signs. We detected SARS-CoV-2 RNA in respiratory secretions and/or feces from all seven animals, live virus in three, and colocalized viral RNA with cellular damage in one. We produced nine whole SARS-CoV-2 genomes from the animals and keepers and identified different SARS-CoV-2 genotypes in the tigers and lions. Epidemiologic and genomic data indicated human-to-tiger transmission. These were the first confirmed cases of natural SARS-CoV-2 animal infections in the United States and the first in nondomestic species in the world. We highlight disease transmission at a nontraditional interface and provide information that contributes to understanding SARS-CoV-2 transmission across species.IMPORTANCE The human-animal-environment interface of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important aspect of the coronavirus disease 2019 (COVID-19) pandemic that requires robust One Health-based investigations. Despite this, few reports describe natural infections in animals or directly link them to human infections using genomic data. In the present study, we describe the first cases of natural SARS-CoV-2 infection in tigers and lions in the United States and provide epidemiological and genetic evidence for human-to-animal transmission of the virus. Our data show that tigers and lions were infected with different genotypes of SARS-CoV-2, indicating two independent transmission events to the animals. Importantly, infected animals shed infectious virus in respiratory secretions and feces. A better understanding of the susceptibility of animal species to SARS-CoV-2 may help to elucidate transmission mechanisms and identify potential reservoirs and sources of infection that are important in both animal and human health.


Subject(s)
Animals, Zoo/virology , Betacoronavirus/physiology , Coronavirus Infections/transmission , Coronavirus Infections/veterinary , Pandemics/veterinary , Panthera/virology , Pneumonia, Viral/transmission , Pneumonia, Viral/veterinary , Animals , Betacoronavirus/classification , Betacoronavirus/genetics , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Genome, Viral/genetics , Haplotypes , Humans , New York City/epidemiology , One Health , Phylogeny , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , SARS-CoV-2 , Zoonoses/epidemiology , Zoonoses/transmission , Zoonoses/virology
10.
Emerg Microbes Infect ; 9(1): 2322-2332, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-838603

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the cause of Coronavirus Disease 2019 (COVID-19) and responsible for the current pandemic. Recent SARS-CoV-2 susceptibility studies in cats show that the virus can replicate in these companion animals and transmit to other cats. Here, we present an in-depth study of SARS-CoV-2 infection, disease and transmission in domestic cats. Cats were challenged with SARS-CoV-2 via intranasal and oral routes. One day post challenge (DPC), two sentinel cats were introduced. Animals were monitored for clinical signs, clinicopathological abnormalities and viral shedding. Postmortem examinations were performed at 4, 7 and 21 DPC. Viral RNA was not detected in blood but transiently in nasal, oropharyngeal and rectal swabs and bronchoalveolar lavage fluid as well as various tissues. Tracheobronchoadenitis of submucosal glands with the presence of viral RNA and antigen was observed in airways of the infected cats. Serology showed that both, principals and sentinels, developed antibodies to SARS-CoV-2. All animals were clinically asymptomatic during the course of the study and capable of transmitting SARS-CoV-2 to sentinels. The results of this study are critical for understanding the clinical course of SARS-CoV-2 in a naturally susceptible host species, and for risk assessment.


Subject(s)
Betacoronavirus/isolation & purification , Cat Diseases/transmission , Coronavirus Infections/transmission , Coronavirus Infections/veterinary , Disease Susceptibility , Pandemics/veterinary , Pneumonia, Viral/transmission , Pneumonia, Viral/veterinary , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Bronchoalveolar Lavage Fluid/chemistry , COVID-19 , Cat Diseases/pathology , Cat Diseases/virology , Cats , Cell Line , Chlorocebus aethiops , Coronavirus Infections/pathology , Male , Pneumonia, Viral/pathology , RNA, Viral/analysis , RNA, Viral/isolation & purification , SARS-CoV-2 , Vero Cells , Virus Replication
11.
Emerg Microbes Infect ; 9(1): 2278-2288, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-811383

ABSTRACT

The emergence of SARS-CoV-2 has resulted in an ongoing global pandemic with significant morbidity, mortality, and economic consequences. The susceptibility of different animal species to SARS-CoV-2 is of concern due to the potential for interspecies transmission, and the requirement for pre-clinical animal models to develop effective countermeasures. In the current study, we determined the ability of SARS-CoV-2 to (i) replicate in porcine cell lines, (ii) establish infection in domestic pigs via experimental oral/intranasal/intratracheal inoculation, and (iii) transmit to co-housed naïve sentinel pigs. SARS-CoV-2 was able to replicate in two different porcine cell lines with cytopathic effects. Interestingly, none of the SARS-CoV-2-inoculated pigs showed evidence of clinical signs, viral replication or SARS-CoV-2-specific antibody responses. Moreover, none of the sentinel pigs displayed markers of SARS-CoV-2 infection. These data indicate that although different porcine cell lines are permissive to SARS-CoV-2, five-week old pigs are not susceptible to infection via oral/intranasal/intratracheal challenge. Pigs are therefore unlikely to be significant carriers of SARS-CoV-2 and are not a suitable pre-clinical animal model to study SARS-CoV-2 pathogenesis or efficacy of respective vaccines or therapeutics.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/veterinary , Pandemics/veterinary , Pneumonia, Viral/veterinary , Swine Diseases/virology , Animals , Betacoronavirus/genetics , Betacoronavirus/immunology , COVID-19 , Cell Line , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Coronavirus Infections/transmission , Disease Models, Animal , Disease Reservoirs , Disease Susceptibility , Female , Male , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Pneumonia, Viral/transmission , RNA, Viral/blood , Reverse Transcriptase Polymerase Chain Reaction/veterinary , SARS-CoV-2 , Swine , Swine Diseases/immunology , Swine Diseases/pathology , Swine Diseases/transmission , Virus Cultivation , Virus Replication , Whole Exome Sequencing
12.
Virol J ; 17(1): 143, 2020 10 02.
Article in English | MEDLINE | ID: covidwho-810398

ABSTRACT

On 11 March 2020, the World Health Organization (WHO) announced Corona Virus Disease (COVID-19), a disease caused by a pathogen called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a pandemic. This ongoing pandemic has now been reported in 215 countries with more than 23 million confirmed cases and more than 803 thousand deaths worldwide as of August 22, 2020. Although efforts are undergoing, there is no approved vaccine or any specific antiretroviral drug to treat COVID-19 so far. It is now known that SARS-CoV-2 can affect not only humans but also pets and other domestic and wild animals, making it a one health global problem. Several published scientific evidence has shown that bats are the initial reservoir hosts of SARS-CoV-2, and pangolins are suggested as an intermediate hosts. So far, little is known concerning the role of pets and other animals in the transmission of COVID-19. Therefore, updated knowledge about the potential role of pets in the current outbreak will be of paramount importance for effective prevention and control of the disease. This review summarized the current evidence about the role of pets and other animals in the transmission of COVID-19.


Subject(s)
Coronavirus Infections/transmission , Coronavirus Infections/veterinary , Pandemics/veterinary , Pets/virology , Pneumonia, Viral/transmission , Pneumonia, Viral/veterinary , Zoonoses/transmission , Animals , Animals, Domestic/virology , Animals, Wild/virology , Betacoronavirus/isolation & purification , COVID-19 , Chiroptera/virology , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Global Health , Humans , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , SARS-CoV-2 , Zoonoses/epidemiology , Zoonoses/prevention & control , Zoonoses/virology
13.
Sci Rep ; 10(1): 16007, 2020 09 29.
Article in English | MEDLINE | ID: covidwho-809120

ABSTRACT

Since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became a pandemic event in the world, it has not only caused huge economic losses, but also a serious threat to global public health. Many scientific questions about SARS-CoV-2 and Coronavirus disease (COVID-19) were raised and urgently need to be answered, including the susceptibility of animals to SARS-CoV-2 infection. Here we tested whether tree shrew, an emerging experimental animal domesticated from wild animal, is susceptible to SARS-CoV-2 infection. No clinical signs were observed in SARS-CoV-2 inoculated tree shrews during this experiment except the increasing body temperature particularly in female animals. Low levels of virus shedding and replication in tissues occurred in all three age groups. Notably, young tree shrews (6 months to 12 months) showed virus shedding at the earlier stage of infection than adult (2 years to 4 years) and old (5 years to 7 years) animals that had longer duration of virus shedding comparatively. Histopathological examine revealed that pulmonary abnormalities were the main changes but mild although slight lesions were also observed in other tissues. In summary, tree shrew is less susceptible to SARS-CoV-2 infection compared with the reported animal models and may not be a suitable animal for COVID-19 related researches. However, tree shrew may be a potential intermediate host of SARS-CoV-2 as an asymptomatic carrier.


Subject(s)
Coronavirus Infections/veterinary , Host Specificity/physiology , Pandemics/veterinary , Pneumonia, Viral/veterinary , Tupaiidae/virology , Animals , Betacoronavirus , COVID-19 , Coronavirus Infections/pathology , Disease Susceptibility/veterinary , Disease Susceptibility/virology , Female , Male , Pneumonia, Viral/pathology , SARS-CoV-2 , Viral Load , Virus Shedding/physiology
14.
Sci Rep ; 10(1): 15917, 2020 09 28.
Article in English | MEDLINE | ID: covidwho-800800

ABSTRACT

SARS-CoV-2 is the novel coronavirus responsible for the outbreak of COVID-19, a disease that has spread to over 100 countries and, as of the 26th July 2020, has infected over 16 million people. Despite the urgent need to find effective therapeutics, research on SARS-CoV-2 has been affected by a lack of suitable animal models. To facilitate the development of medical approaches and novel treatments, we compared the ACE2 receptor, and TMPRSS2 and Furin proteases usage of the SARS-CoV-2 Spike glycoprotein in human and in a panel of animal models, i.e. guinea pig, dog, cat, rat, rabbit, ferret, mouse, hamster and macaque. Here we showed that ACE2, but not TMPRSS2 or Furin, has a higher level of sequence variability in the Spike protein interaction surface, which greatly influences Spike protein binding mode. Using molecular docking simulations we compared the SARS-CoV and SARS-CoV-2 Spike proteins in complex with the ACE2 receptor and showed that the SARS-CoV-2 Spike glycoprotein is compatible to bind the human ACE2 with high specificity. In contrast, TMPRSS2 and Furin are sufficiently similar in the considered hosts not to drive susceptibility differences. Computational analysis of binding modes and protein contacts indicates that macaque, ferrets and hamster are the most suitable models for the study of inhibitory antibodies and small molecules targeting the SARS-CoV-2 Spike protein interaction with ACE2. Since TMPRSS2 and Furin are similar across species, our data also suggest that transgenic animal models expressing human ACE2, such as the hACE2 transgenic mouse, are also likely to be useful models for studies investigating viral entry.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/veterinary , Pandemics/veterinary , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/veterinary , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Amino Acid Sequence/genetics , Angiotensin-Converting Enzyme 2 , Animals , COVID-19 , Cats , Computational Biology/methods , Coronavirus Infections/pathology , Cricetinae , Disease Models, Animal , Dogs , Ferrets , Furin/genetics , Furin/metabolism , Guinea Pigs , Humans , Macaca fascicularis , Mice , Molecular Docking Simulation , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/pathology , Rabbits , Rats , SARS-CoV-2 , Serine Endopeptidases/genetics , Serine Endopeptidases/metabolism
15.
J Virol ; 94(18)2020 08 31.
Article in English | MEDLINE | ID: covidwho-803471

ABSTRACT

The COVID-19 pandemic has caused an unprecedented global public health and economic crisis. The origin and emergence of its causal agent, SARS-CoV-2, in the human population remains mysterious, although bat and pangolin were proposed to be the natural reservoirs. Strikingly, unlike the SARS-CoV-2-like coronaviruses (CoVs) identified in bats and pangolins, SARS-CoV-2 harbors a polybasic furin cleavage site in its spike (S) glycoprotein. SARS-CoV-2 uses human angiotensin-converting enzyme 2 (ACE2) as its receptor to infect cells. Receptor recognition by the S protein is the major determinant of host range, tissue tropism, and pathogenesis of coronaviruses. In an effort to search for the potential intermediate or amplifying animal hosts of SARS-CoV-2, we examined receptor activity of ACE2 from 14 mammal species and found that ACE2s from multiple species can support the infectious entry of lentiviral particles pseudotyped with the wild-type or furin cleavage site-deficient S protein of SARS-CoV-2. ACE2 of human/rhesus monkey and rat/mouse exhibited the highest and lowest receptor activities, respectively. Among the remaining species, ACE2s from rabbit and pangolin strongly bound to the S1 subunit of SARS-CoV-2 S protein and efficiently supported the pseudotyped virus infection. These findings have important implications for understanding potential natural reservoirs, zoonotic transmission, human-to-animal transmission, and use of animal models.IMPORTANCE SARS-CoV-2 uses human ACE2 as a primary receptor for host cell entry. Viral entry mediated by the interaction of ACE2 with spike protein largely determines host range and is the major constraint to interspecies transmission. We examined the receptor activity of 14 ACE2 orthologs and found that wild-type and mutant SARS-CoV-2 lacking the furin cleavage site in S protein could utilize ACE2 from a broad range of animal species to enter host cells. These results have important implications in the natural hosts, interspecies transmission, animal models, and molecular basis of receptor binding for SARS-CoV-2.


Subject(s)
Animal Diseases/metabolism , Animal Diseases/virology , Betacoronavirus/physiology , Coronavirus Infections/veterinary , Pandemics/veterinary , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/veterinary , Receptors, Virus/metabolism , Amino Acid Sequence , Angiotensin-Converting Enzyme 2 , Animals , Betacoronavirus/classification , COVID-19 , Cell Line , Host Specificity , Humans , Models, Molecular , Mutation , Peptidyl-Dipeptidase A/chemistry , Phylogeny , Protein Binding , Protein Domains , Proteolysis , Receptors, Virus/chemistry , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/metabolism , Structure-Activity Relationship , Viral Tropism , Virus Internalization
16.
Proc Natl Acad Sci U S A ; 117(40): 24790-24793, 2020 10 06.
Article in English | MEDLINE | ID: covidwho-780139

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, is considered a zoonotic pathogen mainly transmitted human to human. Few reports indicate that pets may be exposed to the virus. The present report describes a cat suffering from severe respiratory distress and thrombocytopenia living with a family with several members affected by COVID-19. Clinical signs of the cat prompted humanitarian euthanasia and a detailed postmortem investigation to assess whether a COVID-19-like disease was causing the condition. Necropsy results showed the animal suffered from feline hypertrophic cardiomyopathy and severe pulmonary edema and thrombosis. SARS-CoV-2 RNA was only detected in nasal swab, nasal turbinates, and mesenteric lymph node, but no evidence of histopathological lesions compatible with a viral infection were detected. The cat seroconverted against SARS-CoV-2, further evidencing a productive infection in this animal. We conclude that the animal had a subclinical SARS-CoV-2 infection concomitant to an unrelated cardiomyopathy that led to euthanasia.


Subject(s)
Betacoronavirus/isolation & purification , Cardiomyopathy, Hypertrophic/veterinary , Coronavirus Infections/veterinary , Pandemics/veterinary , Pneumonia, Viral/veterinary , Animals , COVID-19 , Cardiomyopathy, Hypertrophic/pathology , Cardiomyopathy, Hypertrophic/virology , Cats , Coronavirus Infections/complications , Coronavirus Infections/pathology , Fatal Outcome , Humans , Incidental Findings , Pneumonia, Viral/complications , Pneumonia, Viral/pathology , SARS-CoV-2
17.
ACS Chem Neurosci ; 11(19): 2903-2905, 2020 10 07.
Article in English | MEDLINE | ID: covidwho-779925

ABSTRACT

Several lines of evidence suggest the presence of severe acute respiratory coronavirus-2 (SARS-CoV-2) in wastewater. The use of sewage water for irrigation is common in many developing countries, and it is only partially treated in the majority of countries with less than 10% of collected wastewater receiving any form of treatment globally. Wastewater is unsafe for human and animal consumption and contains impurities and microbial pathogens. Here, we pose the question of whether the reuse of untreated or partially treated wastewater for irrigation can expose susceptible populations and pets, leading to COVID-19 disease recurrence in the community? It is imperative to study the ecological relationships between humans, animals, and environmental health in relation to COVID-19 to contribute to a "One Health Concept" to design preventative strategies and attain optimal health for people, animals, and the environment.


Subject(s)
Agricultural Irrigation/methods , Coronavirus Infections/transmission , Pneumonia, Viral/transmission , Waste Water/virology , Animals , Animals, Domestic/virology , Betacoronavirus , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/veterinary , Humans , Pandemics/veterinary , Pneumonia, Viral/epidemiology , Pneumonia, Viral/veterinary , Risk Factors , SARS-CoV-2 , Sewage/virology , Water Purification/methods
18.
J Transl Med ; 18(1): 358, 2020 09 21.
Article in English | MEDLINE | ID: covidwho-781481

ABSTRACT

COVID-19 caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated in Wuhan (Hubei province, China) during late 2019. It has spread across the globe affecting nearly 21 million people with a toll of 0.75 million deaths and restricting the movement of most of the world population during the past 6 months. COVID-19 became the leading health, economic, and humanitarian challenge of the twenty-first century. In addition to the considerable COVID-19 cases, hospitalizations, and deaths in humans, several cases of SARS-CoV-2 infections in animal hosts (dog, cat, tiger, lion, and mink) have been reported. Thus, the concern of pet owners is increasing. Moreover, the dynamics of the disease requires further explanation, mainly concerning the transmission of the virus from humans to animals and vice versa. Therefore, this study aimed to gather information about the reported cases of COVID-19 transmission in animals through a literary review of works published in scientific journals and perform genomic and phylogenetic analyses of SARS-CoV-2 isolated from animal hosts. Although many instances of transmission of the SARS-CoV-2 have been reported, caution and further studies are necessary to avoid the occurrence of maltreatment in animals, and to achieve a better understanding of the dynamics of the disease in the environment, humans, and animals. Future research in the animal-human interface can help formulate and implement preventive measures to combat the further transmission of COVID-19.


Subject(s)
Betacoronavirus , Coronavirus Infections/veterinary , Pandemics/veterinary , Pneumonia, Viral/veterinary , Zoonoses/transmission , Animal Husbandry , Animals , Betacoronavirus/classification , Betacoronavirus/genetics , Betacoronavirus/pathogenicity , COVID-19 , Cats , Coronavirus/classification , Coronavirus/genetics , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Disease Reservoirs/veterinary , Disease Reservoirs/virology , Dogs , Genome, Viral , Humans , Mink/virology , Netherlands/epidemiology , Occupational Exposure , Pets/virology , Phylogeny , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics , Zoonoses/epidemiology
19.
Vet Res Commun ; 44(3-4): 119-130, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-756542

ABSTRACT

Coronaviruses are a large family of viruses that are known to infect both humans and animals. However, the evidence of inter-transmission of coronavirus between humans and companion animals is still a debatable issue. There is substantial evidence that the virus outbreak is fueled by zoonotic transmission because this new virus belongs to the same family of viruses as SARS-CoV associated with civet cats, and MERS-CoV associated with dromedary camels. While the whole world is investigating the possibility about the transmission of this virus, the transmission among humans is established, but the interface between humans and animals is not much evident. Not only are the lives of human beings at risk, but there is an equal potential threat to the animal world. With multiple reports claiming about much possibility of transmission of COVID-19 from humans to animals, there has been a significant increase in the number of pets being abandoned by their owners. Additionally, the risk of reverse transmission of COVID-19 virus from companion pets like cats and dogs at home is yet another area of concern. The present article highlights different evidence of human-animal interface and necessitates the precautionary measures required to combat with the consequences of this interface. The Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) have suggested various ways to promote awareness and corroborate practices for helping people as well as animals to stay secure and healthy.


Subject(s)
Betacoronavirus , Coronavirus Infections/transmission , Pneumonia, Viral/transmission , Zoonoses/transmission , Animals , Betacoronavirus/pathogenicity , COVID-19 , Cats/virology , Coronavirus Infections/veterinary , Dogs/virology , Ferrets/virology , Humans , Pandemics/veterinary , Pneumonia, Viral/veterinary , Poultry/virology , SARS-CoV-2 , Swine/virology , Zoonoses/virology
20.
Emerg Microbes Infect ; 9(1): 2013-2019, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-739234

ABSTRACT

COVID-19 is a new respiratory illness caused by SARS-CoV-2, and has constituted a global public health emergency. Cat is susceptible to SARS-CoV-2. However, the prevalence of SARS-CoV-2 in cats remains largely unknown. Here, we investigated the infection of SARS-CoV-2 in cats during COVID-19 outbreak in Wuhan by serological detection methods. A cohort of serum samples were collected from cats in Wuhan, including 102 sampled after COVID-19 outbreak, and 39 prior to the outbreak. Fifteen sera collected after the outbreak were positive for the receptor binding domain (RBD) of SARS-CoV-2 by indirect enzyme linked immunosorbent assay (ELISA). Among them, 11 had SARS-CoV-2 neutralizing antibodies with a titer ranging from 1/20 to 1/1080. No serological cross-reactivity was detected between SARS-CoV-2 and type I or II feline infectious peritonitis virus (FIPV). In addition, we continuously monitored serum antibody dynamics of two positive cats every 10 days over 130 days. Their serum antibodies reached the peak at 10 days after first sampling, and declined to the limit of detection within 110 days. Our data demonstrated that SARS-CoV-2 has infected cats in Wuhan during the outbreak and described serum antibody dynamics in cats, providing an important reference for clinical treatment and prevention of COVID-19.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Betacoronavirus/immunology , Coronavirus Infections/veterinary , Pandemics/veterinary , Pneumonia, Viral/veterinary , Animals , COVID-19 , Cats , China , Coronavirus Infections/epidemiology , Coronavirus Nucleocapsid Proteins , Coronavirus, Feline/immunology , Cross Reactions/immunology , Enzyme-Linked Immunosorbent Assay/methods , Immunoglobulin G/blood , Nucleocapsid Proteins/immunology , Phosphoproteins , Pneumonia, Viral/epidemiology , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/immunology
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