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1.
Conservation Science and Practice ; 2022.
Article in English | Web of Science | ID: covidwho-2070506

ABSTRACT

Unsustainable wildlife trade is a major driver of biodiversity loss and an important public health threat. Yet, effective wildlife trade regulation is currently at odds with food security and economic incentives provided by this global, multibillion-dollar industry. Given such limitations, public health and conservation resources can be aligned to target species for which trade both increases risk of extinction and threatens public health. Here, we developed a simple conservation and health trade risk (CHT) index (range: 2-50) using a case study of traded mammals based on species' extinction and zoonotic risks, weighed by the extent of their trade. We applied this index to 1161 International Union for the Conservation of Nature-listed terrestrial mammals involved in the wildlife trade to identify 284 high-priority species that scored high in the CHT index (CHT >= 18). Species ranking high for conservation, public health, and trade risks include those belonging to the orders Primates, Cetartiodactyla (even-toed ungulates), Rodentia (rodents), Chiroptera (bats), and Carnivora (carnivores). Of the high-priority species, 33% (n = 95) are country-endemics and may be good candidates for trade regulations and enforcement at national scales. Our study provides a preliminary step in prioritizing species, taxonomic groups, and countries for focused wildlife trade regulation to meet both conservation and public health goals.

2.
Annu Rev Virol ; 9(1): 139-156, 2022 09 29.
Article in English | MEDLINE | ID: covidwho-2070601

ABSTRACT

Predicting the evolution of virus host range has proven to be extremely difficult, in part because of the sheer diversity of viruses, each with unique biology and ecological interactions. We have not solved this problem, but to make the problem more tractable, we narrowed our focus to three traits intrinsic to all viruses that may play a role in host-range evolvability: mutation rate, recombination rate, and phenotypic heterogeneity. Although each trait should increase evolvability, they cannot do so unbounded because fitness trade-offs limit the ability of all three traits to maximize evolvability. By examining these constraints, we can begin to identify groups of viruses with suites of traits that make them especially concerning, as well as ecological and environmental conditions that might push evolution toward accelerating host-range expansion.


Subject(s)
Host Specificity , Viruses , Viruses/genetics
3.
J Med Virol ; 2022 Sep 02.
Article in English | MEDLINE | ID: covidwho-2013637

ABSTRACT

Increasing evidence supports inter-species transmission of SARS-CoV-2 variants from humans to domestic or wild animals during the ongoing COVID-19 pandemic, which is posing great challenges to epidemic control. Clarifying the host range of emerging SARS-CoV-2 variants will provide instructive information for the containment of viral spillover. The spike protein (S) of SARS-CoV-2 is the key determinant of receptor utilization, and therefore amino acid mutations on S will probably alter viral host range. Here, to evaluate the impact of S mutations, we tested 27 pseudoviruses of SARS-CoV-2 carrying different spike mutants by infecting Hela cells expressing different angiotensin-converting enzyme 2 (ACE2) orthologs from 20 animals. Of these 27 pseudoviruses, 20 bear single mutation and the other 7 were cloned from emerging SARS-CoV-2 variants, including D614G, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), Lambda (B.1.429), and Mu (B.1.621). Using pseudoviral reporter assay, we identified that the substitutions of T478I and N501Y enabled the pseudovirus to utilize chicken ACE2, indicating potential infectivity to avian species. Furthermore, the S mutants of real SARS-CoV-2 variants comprising N501Y showed significantly acquired abilities to infect cells expressing mouse ACE2, indicating a critical role of N501Y in expanding SARS-CoV-2 host range. In addition, A262S and T478I significantly enhanced the utilization of various mammal ACE2. In summary, our results indicated that T478I and N501Y substitutions were two S mutations important for receptor adaption of SARS-CoV-2, potentially contributing to the spillover of the virus to many other animal hosts. Therefore, more attention should be paid to SARS-CoV-2 variants with these two mutations.

4.
Indian Journal of Animal Sciences ; 92(6):693-700, 2022.
Article in English | CAB Abstracts | ID: covidwho-1975927

ABSTRACT

Emergence of avian infectious bronchitis virus (IBV) variants with altered tissue tropism and host range has been reported from different parts of the world. Little is known about the different IBV variants existing and emerging in India. To explore the same, an IBV isolate, namely B17 isolated from backyard chicken in Tamil Nadu was used in the present study. The complete genome of B17 was sequenced and its phylogenetic relationship with the existing vaccine strain genotypes was analysed. The phylogenetic analysis of both S1 gene and complete genome sequence grouped B17 under Mass41 genotype comprising of M41, Beaudette, H120 and H120 variant with bootstrap value of 95-100%. Further, genomic analysis of B17 revealed the possibilities of emergence of the same from H120 vaccine strain through mutations at various genes.

5.
Transbound Emerg Dis ; 69(4): e799-e813, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1968196

ABSTRACT

Understanding the zoonotic and emerging potential of viruses is critical to prevent and control spread that can cause disease epidemics or pandemics. We developed a database using the most up-to-date information from the International Committee on Taxonomy of Viruses (4958 virus species) and identified 1479 vertebrate virus species and their host ranges. Viral traits and host ranges were then used as predictors in generalized linear mixed models for three host-associated outcomes - confirmed zoonotic, potential zoonotic and disease emergence. We identified significant interactions between host range and viral characteristics, not previously reported, that influence the zoonotic and emergence potential of viruses. Bat- and livestock-adapted viruses posed high risk, and the risk increased substantially if these viruses were also present in other vertebrates or were not reported from invertebrates. Our model predicted 39 viruses of interest that have never been reported to have zoonotic potential (27) or to potentially become emerging human viruses (12). We conclude that nucleic acid type is important in identifying the zoonotic and emerging potential of viruses. We recommend enhanced surveillance and monitoring of these virus species identified with a zoonotic and emerging potential to mitigate disease outbreaks and future epidemics.


Subject(s)
Host Specificity , Viruses , Animals , Humans , Livestock , Pandemics , Viruses/genetics , Zoonoses/epidemiology
6.
Viruses ; 14(5):905, 2022.
Article in English | ProQuest Central | ID: covidwho-1871928

ABSTRACT

Homologs of the human hepatitis E virus (HEV) have been identified in more than a dozen animal species. Some of them have been evidenced to cross species barriers and infect humans. Zoonotic HEV infections cause chronic liver diseases as well as a broad range of extrahepatic manifestations, which increasingly become significant clinical problems. Bats comprise approximately one-fifth of all named mammal species and are unique in their distinct immune response to viral infection. Most importantly, they are natural reservoirs of several highly pathogenic viruses, which have induced severe human diseases. Since the first discovery of HEV-related viruses in bats in 2012, multiple genetically divergent HEV variants have been reported in a total of 12 bat species over the last decade, which markedly expanded the host range of the HEV family and shed light on the evolutionary origin of human HEV. Meanwhile, bat-borne HEV also raised critical public health concerns about its zoonotic potential. Bat HEV strains resemble genomic features but exhibit considerable heterogeneity. Due to the close evolutionary relationships, bat HEV altogether has been recently assigned to an independent genus, Chirohepevirus. This review focuses on the current state of bat HEV and provides novel insights into HEV genetic diversity and molecular evolution.

7.
Environ Res ; 212(Pt C): 113303, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1796871

ABSTRACT

Understanding the origin of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a highly debatable and unresolved issue for scientific communities all over the world. Understanding the mechanism of virus entry to the host cells is crucial to deciphering the susceptibility profiles of animal species to SARS-CoV-2. The interaction of SARS-CoV-2 ligands (receptor-binding domain on spike protein) with its host cell receptor, angiotensin-converting enzyme 2 (ACE2), is a critical determinant of host range and cross-species transmission. In this study, we developed and implemented a rigorous computational approach for predicting binding affinity between 299 ACE2 orthologs from diverse vertebrate species and the SARS-CoV-2 spike protein. The findings show that the SARS-CoV-2 spike protein can bind to a wide range of vertebrate species carrying evolutionary divergent ACE2, implying a broad host range at the virus entry level, which may contribute to cross-species transmission and further viral evolution. Furthermore, the current study facilitated the identification of genetic determinants that may differentiate susceptible from resistant host species based on the conservation of ACE2-spike protein interacting residues in vertebrate host species known to facilitate SARS-CoV-2 infection; however, these genetic determinants warrant in vivo experimental confirmation. The molecular interactions associated with varied binding affinity of distinct ACE2 isoforms in a specific bat species were identified using protein structure analysis, implying the existence of diversified bat species' susceptibility to SARS-CoV-2. The current study's findings highlight the importance of intensive surveillance programmes aimed at identifying susceptible hosts, especially those with the potential to transmit zoonotic pathogens, in order to prevent future outbreaks.


Subject(s)
COVID-19 , Spike Glycoprotein, Coronavirus , Angiotensin-Converting Enzyme 2 , Animals , Humans , Peptidyl-Dipeptidase A/chemistry , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Vertebrates/metabolism
8.
J Gen Virol ; 103(4)2022 04.
Article in English | MEDLINE | ID: covidwho-1774462

ABSTRACT

Following the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in PR China in late 2019 a number of variants have emerged, with two of these - alpha and delta - subsequently growing to global prevalence. One characteristic of these variants are changes within the spike protein, in particular the receptor-binding domain (RBD). From a public health perspective, these changes have important implications for increased transmissibility and immune escape; however, their presence could also modify the intrinsic host range of the virus. Using viral pseudotyping, we examined whether the variants of concern (VOCs) alpha, beta, gamma and delta have differing host angiotensin-converting enzyme 2 (ACE2) receptor usage patterns, focusing on a range of relevant mammalian ACE2 proteins. All four VOCs were able to overcome a previous restriction for mouse ACE2, with demonstrable differences also seen for individual VOCs with rat, ferret or civet ACE2 receptors, changes that we subsequently attributed to N501Y and E484K substitutions within the spike RBD.


Subject(s)
COVID-19 , SARS-CoV-2 , Angiotensin-Converting Enzyme 2/genetics , Animals , Ferrets , Host Specificity , Humans , Mice , Peptidyl-Dipeptidase A/chemistry , Rats , SARS-CoV-2/genetics
9.
Springer Protocol. Handb. ; : 3-19, 2022.
Article in English | EMBASE | ID: covidwho-1718502

ABSTRACT

Coronaviruses (CoVs) infect diverse animal species and cause respiratory, enteric, hepatic, renal, neurologic, and even systemic diseases. The majority of CoVs have a narrow host specificity, but a few CoVs have a broad range of host specificity. This chapter provides a brief review of animal CoVs, including SARS-CoV-2 of animals for their receptors, host tropism, and pathogenesis in target animals.

10.
Genome Biol Evol ; 14(2)2022 02 04.
Article in English | MEDLINE | ID: covidwho-1684680

ABSTRACT

The lack of an identifiable intermediate host species for the proximal animal ancestor of SARS-CoV-2, and the large geographical distance between Wuhan and where the closest evolutionary related coronaviruses circulating in horseshoe bats (members of the Sarbecovirus subgenus) have been identified, is fueling speculation on the natural origins of SARS-CoV-2. We performed a comprehensive phylogenetic study on SARS-CoV-2 and all the related bat and pangolin sarbecoviruses sampled so far. Determining the likely recombination events reveals a highly reticulate evolutionary history within this group of coronaviruses. Distribution of the inferred recombination events is nonrandom with evidence that Spike, the main target for humoral immunity, is beside a recombination hotspot likely driving antigenic shift events in the ancestry of bat sarbecoviruses. Coupled with the geographic ranges of their hosts and the sampling locations, across southern China, and into Southeast Asia, we confirm that horseshoe bats, Rhinolophus, are the likely reservoir species for the SARS-CoV-2 progenitor. By tracing the recombinant sequence patterns, we conclude that there has been relatively recent geographic movement and cocirculation of these viruses' ancestors, extending across their bat host ranges in China and Southeast Asia over the last 100 years. We confirm that a direct proximal ancestor to SARS-CoV-2 has not yet been sampled, since the closest known relatives collected in Yunnan shared a common ancestor with SARS-CoV-2 approximately 40 years ago. Our analysis highlights the need for dramatically more wildlife sampling to: 1) pinpoint the exact origins of SARS-CoV-2's animal progenitor, 2) the intermediate species that facilitated transmission from bats to humans (if there is one), and 3) survey the extent of the diversity in the related sarbecoviruses' phylogeny that present high risk for future spillovers.


Subject(s)
Chiroptera/virology , Coronavirus/genetics , Pangolins/virology , Phylogeny , Recombination, Genetic , Animals , Humans , Phylogeography
11.
Viruses ; 14(1)2021 12 24.
Article in English | MEDLINE | ID: covidwho-1580408

ABSTRACT

The emergence of new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern pose a major threat to public health, due to possible enhanced virulence, transmissibility and immune escape. These variants may also adapt to new hosts, in part through mutations in the spike protein. In this study, we evaluated the infectivity and pathogenicity of SARS-CoV-2 variants of concern in wild-type C57BL/6 mice. Six-week-old mice were inoculated intranasally with a representative virus from the original B.1 lineage, or the emerging B.1.1.7 and B.1.351 lineages. We also infected a group of mice with a mouse-adapted SARS-CoV-2 (MA10). Viral load and mRNA levels of multiple cytokines and chemokines were analyzed in the lung tissues on day 3 after infection. Our data show that unlike the B.1 virus, the B.1.1.7 and B.1.351 viruses are capable of infecting C57BL/6 mice and replicating at high concentrations in the lungs. The B.1.351 virus replicated to higher titers in the lungs compared with the B.1.1.7 and MA10 viruses. The levels of cytokines (IL-6, TNF-α, IL-1ß) and chemokine (CCL2) were upregulated in response to the B.1.1.7 and B.1.351 infection in the lungs. In addition, robust expression of viral nucleocapsid protein and histopathological changes were detected in the lungs of B.1.351-infected mice. Overall, these data indicate a greater potential for infectivity and adaptation to new hosts by emerging SARS-CoV-2 variants.


Subject(s)
COVID-19/virology , SARS-CoV-2/physiology , SARS-CoV-2/pathogenicity , Animals , COVID-19/immunology , COVID-19/pathology , Cytokines/immunology , Disease Models, Animal , Host Specificity , Inflammation , Lung/immunology , Lung/pathology , Lung/virology , Mice , Mice, Inbred C57BL , Viral Load , Virus Replication
12.
Front Public Health ; 9: 717941, 2021.
Article in English | MEDLINE | ID: covidwho-1477889

ABSTRACT

Coronaviruses cause respiratory and digestive diseases in vertebrates. The recent pandemic, caused by the novel severe acute respiratory syndrome (SARS) coronavirus 2, is taking a heavy toll on society and planetary health, and illustrates the threat emerging coronaviruses can pose to the well-being of humans and other animals. Coronaviruses are constantly evolving, crossing host species barriers, and expanding their host range. In the last few decades, several novel coronaviruses have emerged in humans and domestic animals. Novel coronaviruses have also been discovered in captive wildlife or wild populations, raising conservation concerns. The evolution and emergence of novel viruses is enabled by frequent cross-species transmission. It is thus crucial to determine emerging coronaviruses' potential for infecting different host species, and to identify the circumstances under which cross-species transmission occurs in order to mitigate the rate of disease emergence. Here, I review (broadly across several mammalian host species) up-to-date knowledge of host range and circumstances concerning reported cross-species transmission events of emerging coronaviruses in humans and common domestic mammals. All of these coronaviruses had similar host ranges, were closely related (indicative of rapid diversification and spread), and their emergence was likely associated with high-host-density environments facilitating multi-species interactions (e.g., shelters, farms, and markets) and the health or well-being of animals as end- and/or intermediate spillover hosts. Further research is needed to identify mechanisms of the cross-species transmission events that have ultimately led to a surge of emerging coronaviruses in multiple species in a relatively short period of time in a world undergoing rapid environmental change.


Subject(s)
COVID-19 , Severe Acute Respiratory Syndrome , Animals , Humans , Mammals , Pandemics , SARS-CoV-2 , Severe Acute Respiratory Syndrome/epidemiology
13.
3 Biotech ; 10(11): 483, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-1384661

ABSTRACT

SARS-CoV-2, which causes severe pneumonia epidemics, probably originated from Chinese horseshoe bats, but the intermediate and host range is still unknown. ACE2 is the entry receptor for SARS-CoV-2. The binding capacity of SARS-CoV-2 spike protein to ACE2 is the critical determinant of viral host range and cross-species infection. Here, we used an in silico approach to predict the potential animals range with high susceptibility to SARS-CoV-2 by modelling and studying the Spike-ACE2 interaction of 22 domestic and wild animals. Our results showed that all studied animals are potentially susceptible to SARS-CoV-2 infection with a slight difference in the binding affinity and stability of their ACE2-RBD complexes. Furthermore, we identified a specific substitution of tyrosine to histidine at position 41 in ACE2 that likely reduces the affinity to SARS-CoV-2 in horses and greater horseshoe bats. These results may help to provide important insights into SARS-CoV-2 host range which will make it possible to control the spread of the virus and identify animal models that could be used for screening antiviral drugs or vaccine candidates against SARS-CoV-2.

14.
Virus Evol ; 6(2): veaa078, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-1383237

ABSTRACT

To better understand the genetic diversity, host associations and evolution of coronaviruses (CoVs) in China we analyzed a total of 696 rodents encompassing 16 different species sampled from Zhejiang and Yunnan provinces. Based on reverse transcriptase PCR-based CoV screening of fecal samples and subsequent sequence analysis of the RNA-dependent RNA polymerase gene, we identified CoVs in diverse rodent species, comprising Apodemus agrarius, Apodemus chevrieri, Apodemus latronum, Bandicota indica, Eothenomys cachinus, Eothenomys miletus, Rattus andamanensis, Rattus norvegicus, and Rattus tanezumi. CoVs were particularly commonplace in A. chevrieri, with a detection rate of 12.44 per cent (24/193). Genetic and phylogenetic analysis revealed the presence of three groups of CoVs carried by a range of rodents that were closely related to the Lucheng Rn rat CoV (LRNV), China Rattus CoV HKU24 (ChRCoV_HKU24), and Longquan Rl rat CoV (LRLV) identified previously. One newly identified A. chevrieri-associated virus closely related to LRNV lacked an NS2 gene. This virus had a similar genetic organization to AcCoV-JC34, recently discovered in the same rodent species in Yunnan, suggesting that it represents a new viral subtype. Notably, additional variants of LRNV were identified that contained putative non-structural (NS)2b genes located downstream of the NS2 gene that were likely derived from the host genome. Recombination events were also identified in the open reading frame (ORF) 1a gene of Lijiang-71. In sum, these data reveal the substantial genetic diversity and genomic complexity of rodent-borne CoVs, and extend our knowledge of these major wildlife virus reservoirs.

15.
Vet Q ; 41(1): 181-201, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1202174

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, previously 2019-nCoV) is suspected of having originated in 2019 in China from a coronavirus infected bat of the genus Rhinolophus. Following the initial emergence, possibly facilitated by a mammalian bridge host, SARS-CoV-2 is currently transmitted across the globe via efficient human-to-human transmission. Results obtained from experimental studies indicate that animal species such as cats, ferrets, raccoon dogs, cynomolgus macaques, rhesus macaques, white-tailed deer, rabbits, Egyptian fruit bats, and Syrian hamsters are susceptible to SARS-CoV-2 infection, and that cat-to-cat and ferret-to-ferret transmission can take place via contact and air. However, natural infections of SARS-CoV-2 have been reported only in pet dogs and cats, tigers, lions, snow leopards, pumas, and gorillas at zoos, and farmed mink and ferrets. Even though human-to-animal spillover has been reported at several instances, SARS-CoV-2 transmission from animals-to-humans has only been reported from mink-to-humans in mink farms. Following the rapid transmission of SARS-CoV-2 within the mink population, a new mink-associated SARS-CoV-2 variant emerged that was identified in both humans and mink. The increasing reports of SARS-CoV-2 in carnivores indicate the higher susceptibility of animal species belonging to this order. The sporadic reports of SARS-CoV-2 infection in domestic and wild animal species require further investigation to determine if SARS-CoV-2 or related Betacoronaviruses can get established in kept, feral or wild animal populations, which may eventually act as viral reservoirs. This review analyzes the current evidence of SARS-CoV-2 natural infection in domestic and wild animal species and their possible implications on public health.


Subject(s)
Animals, Domestic , Animals, Wild , COVID-19/veterinary , Disease Reservoirs/veterinary , Public Health , SARS-CoV-2 , Animals , Animals, Zoo , COVID-19/epidemiology , COVID-19/transmission , Humans
16.
mBio ; 12(2)2021 03 16.
Article in English | MEDLINE | ID: covidwho-1138305

ABSTRACT

The angiotensin-converting enzyme 2 (ACE2) receptor is a major severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) host range determinant, and understanding SARS-CoV-2-ACE2 interactions will provide important insights into COVID-19 pathogenesis and animal model development. SARS-CoV-2 cannot infect mice due to incompatibility between its receptor binding domain and the murine ACE2 receptor. Through molecular modeling and empirical in vitro validation, we identified 5 key amino acid differences between murine and human ACE2 that mediate SARS-CoV-2 infection, generating a chimeric humanized murine ACE2. Additionally, we examined the ability of the humanized murine ACE2 receptor to permit infection by an additional preemergent group 2B coronavirus, WIV-1, providing evidence for the potential pan-virus capabilities of this chimeric receptor. Finally, we predicted the ability of these determinants to inform host range identification of preemergent coronaviruses by evaluating hot spot contacts between SARS-CoV-2 and additional potential host receptors. Our results identify residue determinants that mediate coronavirus receptor usage and host range for application in SARS-CoV-2 and emerging coronavirus animal model development.IMPORTANCE SARS-CoV-2 (the causative agent of COVID-19) is a major public health threat and one of two related coronaviruses that have caused epidemics in modern history. A method of screening potential infectible hosts for preemergent and future emergent coronaviruses would aid in mounting rapid response and intervention strategies during future emergence events. Here, we evaluated determinants of SARS-CoV-2 receptor interactions, identifying key changes that enable or prevent infection. The analysis detailed in this study will aid in the development of model systems to screen emergent coronaviruses as well as treatments to counteract infections.


Subject(s)
Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme 2/metabolism , Betacoronavirus/physiology , Virus Replication , Amino Acid Sequence , Angiotensin-Converting Enzyme 2/genetics , Animals , Betacoronavirus/metabolism , Binding Sites , COVID-19/virology , Cell Line , Coronavirus Infections/virology , Host Specificity , Humans , Mice , Models, Molecular , Mutation , Protein Binding , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , SARS-CoV-2/metabolism , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism
17.
Proc Natl Acad Sci U S A ; 118(12)2021 03 23.
Article in English | MEDLINE | ID: covidwho-1117490

ABSTRACT

The pandemic of COVID-19, caused by SARS-CoV-2, is a major global health threat. Epidemiological studies suggest that bats (Rhinolophus affinis) are the natural zoonotic reservoir for SARS-CoV-2. However, the host range of SARS-CoV-2 and intermediate hosts that facilitate its transmission to humans remain unknown. The interaction of coronavirus with its host receptor is a key genetic determinant of host range and cross-species transmission. SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) as the receptor to enter host cells in a species-dependent manner. In this study, we characterized the ability of ACE2 from diverse species to support viral entry. By analyzing the conservation of five residues in two virus-binding hotspots of ACE2 (hotspot 31Lys and hotspot 353Lys), we predicted 80 ACE2 proteins from mammals that could potentially mediate SARS-CoV-2 entry. We chose 48 ACE2 orthologs among them for functional analysis, and showed that 44 of these orthologs-including domestic animals, pets, livestock, and animals commonly found in zoos and aquaria-could bind the SARS-CoV-2 spike protein and support viral entry. In contrast, New World monkey ACE2 orthologs could not bind the SARS-CoV-2 spike protein and support viral entry. We further identified the genetic determinant of New World monkey ACE2 that restricts viral entry using genetic and functional analyses. These findings highlight a potentially broad host tropism of SARS-CoV-2 and suggest that SARS-CoV-2 might be distributed much more widely than previously recognized, underscoring the necessity to monitor susceptible hosts to prevent future outbreaks.


Subject(s)
Angiotensin-Converting Enzyme 2/genetics , COVID-19/veterinary , Receptors, Virus/genetics , SARS-CoV-2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Animals , COVID-19/genetics , COVID-19/metabolism , COVID-19/virology , Host Specificity , Humans , Pandemics/prevention & control , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Phylogeny , Protein Binding , Receptors, Virus/metabolism , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Viral Tropism , Viral Zoonoses/genetics , Viral Zoonoses/prevention & control , Viral Zoonoses/virology , Virus Attachment , Virus Internalization
18.
Onderstepoort J Vet Res ; 88(1): e1-e8, 2021 Feb 10.
Article in English | MEDLINE | ID: covidwho-1077469

ABSTRACT

Human coronaviruses are known respiratory pathogens associated with a range of respiratory illnesses, and there are considerable morbidity and hospitalisation amongst immune-compromised individuals of all age groups. The emergence of a highly pathogenic human coronavirus in China in 2019 has confirmed the long-held opinion that these viruses are important emerging and re-emerging pathogens. In this review article, we trace the discovery and emergence of coronaviruses (CoVs) over time since they were first reported. The review article will enrich our understanding on the host range, diversity and evolution, transmission of human CoVs and the threat posed by these viruses circulating in animal populations but overtime have spilled over to humans because of the increased proximity between humans and animals.


Subject(s)
Communicable Diseases, Emerging/virology , Coronavirus Infections/virology , Coronavirus/classification , Animals , Coronavirus/genetics , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Disease Outbreaks , Host Specificity , Humans
19.
Vaccines (Basel) ; 8(4)2020 Oct 06.
Article in English | MEDLINE | ID: covidwho-969471

ABSTRACT

Among the four genera of influenza viruses (IVs) and the four genera of coronaviruses (CoVs), zoonotic αIV and ßCoV have occasionally caused airborne epidemic outbreaks in humans, who are immunologically naïve, and the outbreaks have resulted in high fatality rates as well as social and economic disruption and losses. The most devasting influenza A virus (IAV) in αIV, pandemic H1N1 in 1918, which caused at least 40 million deaths from about 500 million cases of infection, was the first recorded emergence of IAVs in humans. Usually, a novel human-adapted virus replaces the preexisting human-adapted virus. Interestingly, two IAV subtypes, A/H3N2/1968 and A/H1N1/2009 variants, and two lineages of influenza B viruses (IBV) in ßIV, B/Yamagata and B/Victoria lineage-like viruses, remain seasonally detectable in humans. Both influenza C viruses (ICVs) in γIV and four human CoVs, HCoV-229E and HCoV-NL63 in αCoV and HCoV-OC43 and HCoV-HKU1 in ßCoV, usually cause mild respiratory infections. Much attention has been given to CoVs since the global epidemic outbreaks of ßSARS-CoV in 2002-2004 and ßMERS-CoV from 2012 to present. ßSARS-CoV-2, which is causing the ongoing COVID-19 pandemic that has resulted in 890,392 deaths from about 27 million cases of infection as of 8 September 2020, has provoked worldwide investigations of CoVs. With the aim of developing efficient strategies for controlling virus outbreaks and recurrences of seasonal virus variants, here we overview the structures, diversities, host ranges and host receptors of all IVs and CoVs and critically review current knowledge of receptor binding specificity of spike glycoproteins, which mediates infection, of IVs and of zoonotic, pandemic and seasonal CoVs.

20.
Infect Genet Evol ; 87: 104670, 2021 01.
Article in English | MEDLINE | ID: covidwho-959997

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causing agent of Coronavirus Disease-2019 (COVID-19), is likely to be originated from bat and transmitted through intermediate hosts. However, the immediate source species of SARS-CoV-2 have not yet been confirmed. Here, we used diversity analysis of the angiotensin I converting enzyme 2 (ACE2) that serves as cellular receptor for SARS-CoV-2 and transmembrane protease serine 2 (TMPRSS2), which has been proved to be utilized by SARS-CoV-2 for spike protein priming. We also simulated the structure of receptor-binding domain of SARS-CoV-2 spike protein (SARS-CoV-2S RBD) with the ACE2s to investigate their binding affinity to determine the potential intermediate animal hosts that could spread the SARS-CoV-2 to humans in South Asia. We identified cow, buffalo, goat and sheep, which are predominant species in the household farming system in South Asia that can potentially be infected by SARS-CoV-2. All the bird species studied along with rat and mouse were considered less potential to interact with SARS-CoV-2. The interaction interfaces of SARS-CoV-2S RBD and ACE2 protein complex suggests pangolin as a potential intermediate host in SARS-CoV-2. Our results provide a valuable resource for the identification of potential hosts for SARS-CoV-2 in South Asia and henceforth reduce the opportunity for a future outbreak of COVID-19.


Subject(s)
COVID-19/transmission , Disease Vectors/classification , Angiotensin-Converting Enzyme 2/genetics , Animals , Asia/epidemiology , COVID-19/epidemiology , COVID-19/virology , Humans , Phylogeny , SARS-CoV-2/isolation & purification , Serine Endopeptidases/genetics , Species Specificity
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