ACE2 partially dictates the host range and tropism of SARS-CoV-2.

COVID-19, which is caused by SARS-CoV-2, has been declared a global pandemic. Although effective strategies have been applied to treat the disease, much is still unknown about this novel virus. SARS-CoV-2 enters host cells through ACE2, which is a component of the angiotensin-regulating system. Binding of the SARS-CoV-2 S protein to ACE2 is a prerequisite for SARS-CoV-2 infection. Many studies have indicated a close relationship between ACE2 expression and SARS-CoV-2 infection. The structural basis of receptor recognition by SARS-CoV-2 has been analyzed in detail. The diversification of the ACE2 sequence due to ACE2 polymorphisms and alternative splicing has to a large extent affected the susceptibility of different species. Differential ACE2 expression makes specific populations more prone to be infected, and ACE2 also plays a role in the broad tropism of SARS-CoV-2 in human organs and tissues. In this review, we comprehensively summarize how the ACE2 expression profile affects the host range and tropism of SARS-CoV-2, which will provide mechanistic insights into the susceptibilities and outcomes of SARS-CoV-2 infection.

Evolution of Immune Evasion and Host Range Expansion by the SARS-CoV-2 B.1.1.529 (Omicron) Variant.

Recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant B.1.1.529 (Omicron) has rapidly become the dominant strain, with an unprecedented number of mutations within its spike gene. However, it remains unknown whether these variants have alterations in their entry efficiency, host tropism, and sensitivity to neutralizing antibodies and entry inhibitors. In this study, we found that Omicron spike has evolved to escape neutralization by three-dose inactivated-vaccine-elicited immunity but remains sensitive to an angiotensin-converting enzyme 2 (ACE2) decoy receptor. Moreover, Omicron spike could use human ACE2 with a slightly increased efficiency while gaining a significantly increased binding affinity for a mouse ACE2 ortholog, which exhibits limited binding with wild-type (WT) spike. Furthermore, Omicron could infect wild-type C57BL/6 mice and cause histopathological changes in the lungs. Collectively, our results reveal that evasion of neutralization by vaccine-elicited antibodies and enhanced human and mouse ACE2 receptor engagement may contribute to the expanded host range and rapid spread of the Omicron variant. IMPORTANCE The recently emerged SARS-CoV-2 Omicron variant with numerous mutations in the spike protein has rapidly become the dominant strain, thereby raising concerns about the effectiveness of vaccines. Here, we found that the Omicron variant exhibits a reduced sensitivity to serum neutralizing activity induced by a three-dose inactivated vaccine but remains sensitive to entry inhibitors or an ACE2-Ig decoy receptor. Compared with the ancestor strain isolated in early 2020, the spike protein of Omicron utilizes the human ACE2 receptor with enhanced efficiency while gaining the ability to utilize mouse ACE2 for cell entry. Moreover, Omicron could infect wild-type mice and cause pathological changes in the lungs. These results reveal that antibody evasion, enhanced human ACE2 utilization, and an expanded host range may contribute to its rapid spread.

Bioinformatics approaches for unveiling virus-host interactions.

The coronavirus disease-2019 (COVID-19) pandemic has elucidated major limitations in the capacity of medical and research institutions to appropriately manage emerging infectious diseases. We can improve our understanding of infectious diseases by unveiling virus-host interactions through host range prediction and protein-protein interaction prediction. Although many algorithms have been developed to predict virus-host interactions, numerous issues remain to be solved, and the entire network remains veiled. In this review, we comprehensively surveyed algorithms used to predict virus-host interactions. We also discuss the current challenges, such as dataset biases toward highly pathogenic viruses, and the potential solutions. The complete prediction of virus-host interactions remains difficult; however, bioinformatics can contribute to progress in research on infectious diseases and human health.

Key mutations on spike protein altering ACE2 receptor utilization and potentially expanding host range of emerging SARS-CoV-2 variants.

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.

The past, current and future epidemiological dynamic of SARS-CoV-2.

SARS-CoV-2, the agent of the COVID-19 pandemic, emerged in late 2019 in China, and rapidly spread throughout the world to reach all continents. As the virus expanded in its novel human host, viral lineages diversified through the accumulation of around two mutations a month on average. Different viral lineages have replaced each other since the start of the pandemic, with the most successful Alpha, Delta and Omicron variants of concern (VoCs) sequentially sweeping through the world to reach high global prevalence. Neither Alpha nor Delta was characterized by strong immune escape, with their success coming mainly from their higher transmissibility. Omicron is far more prone to immune evasion and spread primarily due to its increased ability to (re-)infect hosts with prior immunity. As host immunity reaches high levels globally through vaccination and prior infection, the epidemic is expected to transition from a pandemic regime to an endemic one where seasonality and waning host immunization are anticipated to become the primary forces shaping future SARS-CoV-2 lineage dynamics. In this review, we consider a body of evidence on the origins, host tropism, epidemiology, genomic and immunogenetic evolution of SARS-CoV-2 including an assessment of other coronaviruses infecting humans. Considering what is known so far, we conclude by delineating scenarios for the future dynamic of SARS-CoV-2, ranging from the good-circulation of a fifth endemic 'common cold' coronavirus of potentially low virulence, the bad-a situation roughly comparable with seasonal flu, and the ugly-extensive diversification into serotypes with long-term high-level endemicity.

First serological evidence of SARS-CoV-2 natural infection in small ruminants : Brief report.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) emerged in late December 2019 and spread worldwide, quickly becoming a pandemic. This zoonotic coronavirus shows a broad host range, including wildlife and domestic animals. Small ruminants are shown to be susceptible to SARS-CoV-2 but, to date, no natural infection has been reported. Herein, we performed a survey for SARS-CoV-2 among sheep and goats in the Campania region of Italy using an indirect multispecies ELISA. Next, positive sera were submitted to virus serum neutralization for the quantification of specific neutralizing antibodies. Out of 612 sheep and goats, 23 were found ELISA positive (3.75%) and 1 of them showed 1:20 neutralizing antibodies titer. No significant difference was found between the two species, as well as between male and female, geographical location and age. Our findings demonstrate that natural infection can occur in flocks in a field situation. Moreover, low susceptibility to SARS-CoV-2 is reported for sheep and goats, nevertheless, the continuous mutations of this virus open new scenarios on viral host range and tropism, highlighting the importance of investigating animal species that could represent ongoing or future possible hosts.

Animal Coronaviruses: A Brief Introduction

Coronaviruses (CoVs) are single-stranded positive-sense enveloped RNA viruses. Among RNA viruses, CoVs have the largest genome. CoVs infect diverse animal species including domestic and wild animals. In this chapter, we provide a brief review on animal CoVs by discussing their receptor, host specificity, reverse genetics, and emerging and re-emerging porcine CoVs. Copyright © Springer Science+Business Media New York 2016.

Variation in the ACE2 receptor has limited utility for SARS-CoV-2 host prediction.

Transmission of SARS-CoV-2 from humans to other species threatens wildlife conservation and may create novel sources of viral diversity for future zoonotic transmission. A variety of computational heuristics have been developed to pre-emptively identify susceptible host species based on variation in the angiotensin-converting enzyme 2 (ACE2) receptor used for viral entry. However, the predictive performance of these heuristics remains unknown. Using a newly compiled database of 96 species, we show that, while variation in ACE2 can be used by machine learning models to accurately predict animal susceptibility to sarbecoviruses (accuracy = 80.2%, binomial confidence interval [CI]: 70.8-87.6%), the sites informing predictions have no known involvement in virus binding and instead recapitulate host phylogeny. Models trained on host phylogeny alone performed equally well (accuracy = 84.4%, CI: 75.5-91.0%) and at a level equivalent to retrospective assessments of accuracy for previously published models. These results suggest that the predictive power of ACE2-based models derives from strong correlations with host phylogeny rather than processes which can be mechanistically linked to infection biology. Further, biased availability of ACE2 sequences misleads projections of the number and geographic distribution of at-risk species. Models based on host phylogeny reduce this bias, but identify a very large number of susceptible species, implying that model predictions must be combined with local knowledge of exposure risk to practically guide surveillance. Identifying barriers to viral infection or onward transmission beyond receptor binding and incorporating data which are independent of host phylogeny will be necessary to manage the ongoing risk of establishment of novel animal reservoirs of SARS-CoV-2.

The COVID-19 pandemic affects humans, but also many of the animals we interact with. So far, humans have transmitted the SARS-CoV-2 virus to pet dogs and cats, a wide range of zoo animals, and even wildlife. Transmission of SARS-CoV-2 from humans to animals can lead to outbreaks amongst certain species, which can endanger animal populations and create new sources of human infections. Thus, careful monitoring of animal infections may help protect both animals and humans. Identifying which animals are susceptible to SARS-CoV-2 would help scientists monitor these species for outbreaks and viral circulation. Unfortunately, testing whether SARS-CoV-2 can infect different species in the laboratory is both time-consuming and expensive. To overcome this obstacle, researchers have used computational methods and existing data about the structure and genetic sequences of ACE2 receptors ­ the proteins on the cell surface that SARS-CoV-2 uses to enter the cell ­ to predict SARS-COV-2 susceptibility in different species. However, it remained unclear how accurate this approach was at predicting susceptibility in different animals, or whether their correct predictions indicated causal links between ACE2 variability and SARS-CoV-2 susceptibility. To assess the usefulness of this approach, Mollentze et al. started by using data on the ACE2 receptors from 96 different species and building a machine learning model to predict how susceptible those species might be to SARS-CoV-2. The susceptibility of these species had either been observed in natural infections ­ in zoos, for example ­ or had been assessed in the laboratory, so Mollentze et al. were able to use this information to determine how good both their model and previous approaches based on the sequence of ACE2 receptors were. The results showed that while the model was quite accurate (it correctly predicted susceptibility to SARS-CoV-2 about 80% of the time), its predictions were based on regions of the ACE2 receptors that were not known to interact with the virus. Instead, the regions that the machine learning model relied on were ones that tend to vary more the more distantly related two species are. This indicates that existing computational approaches are likely not relying on information about how ACE2 receptors interact with SARS-CoV-2 to predict susceptibility. Instead, they are simply using information on how closely related the different animal species are, which is much easier to source than data about ACE2 receptors. Indeed, the sequences of the ACE2 receptors in many species are unknown and the species for which this information is available come only from a few geographic areas. Mollentze et al. also showed that limiting the predictions about susceptibility to these species could mislead scientists when deciding which species and geographic areas to surveil for possible viral circulation. Instead, it may be more effective and cost-efficient to use animal relatedness to predict susceptibility to SARS-CoV-2. This makes it possible to make predictions for nearly all mammals, while being just as accurate as models based on ACE2 receptor data. However, Mollentze et al. point out that this approach would still fail to narrow down the number of animals that need to be monitored enough for it to be practical. Considering additional factors like how often the animals interact with humans or how prone they are to transmit the virus among themselves may help narrow it down more. Further research is therefore needed to identify the best multifactor approaches to identifying which animal populations should be monitored.

Aligning conservation and public health goals to tackle unsustainable trade of mammals

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.

A Trait-Based Approach to Predicting Viral Host-Range Evolvability.

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.

Complete genome sequence and phylogenetic analysis of avian infectious bronchitis virus isolated in India

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.

Inherent virus characteristics and host range drive the zoonotic and emerging potential of viruses.

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.

Chirohepevirus from Bats: Insights into Hepatitis E Virus Diversity and Evolution

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.

A novel structure-based approach for identification of vertebrate susceptibility to SARS-CoV-2: Implications for future surveillance programmes.

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.

SARS-CoV-2 variants of concern alpha, beta, gamma and delta have extended ACE2 receptor host ranges.

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.

Animal Coronaviruses

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.

Exploring the Natural Origins of SARS-CoV-2 in the Light of Recombination.

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.

SARS-CoV-2 Variants of Concern Infect the Respiratory Tract and Induce Inflammatory Response in Wild-Type Laboratory Mice.

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.

Cross-Species Transmission of Coronaviruses in Humans and Domestic Mammals, What Are the Ecological Mechanisms Driving Transmission, Spillover, and Disease Emergence?

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.

In silico analysis of ACE2 orthologues to predict animal host range with high susceptibility to SARS-CoV-2.

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.