Rhinolophus Research Articles

Expanded ACE2 dependencies of diverse SARS-like coronavirus receptor binding domains.

Viral spillover from animal reservoirs can trigger public health crises and cripple the world economy. Knowing which viruses are primed for zoonotic transmission can focus surveillance efforts and mitigation strategies for future pandemics. Successful engagement of receptor protein orthologs is necessary during cross-species transmission. The clade 1 sarbecoviruses including Severe Acute Respiratory Syndrome-related Coronavirus (SARS-CoV) and SARS-CoV-2 enter cells via engagement of angiotensin converting enzyme-2 (ACE2), while the receptor for clade 2 and clade 3 remains largely uncharacterized. We developed a mixed cell pseudotyped virus infection assay to determine whether various clades 2 and 3 sarbecovirus spike proteins can enter HEK 293T cells expressing human or Rhinolophus horseshoe bat ACE2 proteins. The receptor binding domains from BtKY72 and Khosta-2 used human ACE2 for entry, while BtKY72 and Khosta-1 exhibited widespread use of diverse rhinolophid ACE2s. A lysine at ACE2 position 31 appeared to be a major determinant of the inability of these RBDs to use a certain ACE2 sequence. The ACE2 protein from Rhinolophus alcyone engaged all known clade 3 and clade 1 receptor binding domains. We observed little use of Rhinolophus ACE2 orthologs by the clade 2 viruses, supporting the likely use of a separate, unknown receptor. Our results suggest that clade 3 sarbecoviruses from Africa and Europe use Rhinolophus ACE2 for entry, and their spike proteins appear primed to contribute to zoonosis under the right conditions.

Broader-species receptor binding and structural bases of Omicron SARS-CoV-2 to both mouse and palm-civet ACE2s

The Omicron variant of SARS-CoV-2 carries multiple unusual mutations, particularly in the receptor-binding domain (RBD) of the spike (S) protein. Moreover, host-adapting mutations, such as residues 493, 498, and 501, were also observed in the Omicron RBD, which indicates that it is necessary to evaluate the interspecies transmission risk of the Omicron variant. Herein, we evaluated the interspecies recognition of the Omicron BA.1 and Delta RBDs by 27 ACE2 orthologs, including humans. We found that Omicron BA.1 expanded its receptor binding spectra to palm-civet, rodents, more bats (least horseshoe bat and greater horseshoe bat) and lesser hedgehog tenrec. Additionally, we determined the cryo-electron microscopy (cryo-EM) structure of the Omicron BA.1 S protein complexed with mouse ACE2 (mACE2) and the crystal structure of Omicron RBD complexed with palm-civet ACE2 (cvACE2). Several key residues for the host range have been identified. These results suggest that surveillance should be enhanced on the Omicron variant for its broader-species receptor binding to prevent spillover and expansion of reservoir hosts for a prolonged pandemic.

A map of bat virus receptors derived from single-cell multiomics

Bats are considered reservoirs of many lethal zoonotic viruses and have been implicated in several outbreaks of emerging infectious diseases, such as SARS-CoV, MERS-CoV, and SARS-CoV-2. It is necessary to systematically derive the expression patterns of bat virus receptors and their regulatory features for future research into bat-borne viruses and the prediction and prevention of pandemics. Here, we performed single-nucleus RNA sequencing (snRNA-seq) and single-nucleus assay for transposase-accessible chromatin using sequencing (snATAC-seq) of major organ samples collected from Chinese horseshoe bats (Rhinolophus affinis) and systematically checked the expression pattern of bat-related virus receptors and chromatin accessibility across organs and cell types, providing a valuable dataset for studying the nature of infection among bat-borne viruses.

Variation in synonymous nucleotide composition among genomes of sarbecoviruses and consequences for the origin of COVID-19

The subgenus Sarbecovirus includes two human viruses, SARS-CoV and SARS-CoV-2, respectively responsible for the SARS epidemic and COVID-19 pandemic, as well as many bat viruses and two pangolin viruses.Here, the synonymous nucleotide composition (SNC) of Sarbecovirus genomes was analysed by examining third codon-positions, dinucleotides, and degenerate codons. The results show evidence for the eight following groups: (i) SARS-CoV related coronaviruses (SCoVrC including many bat viruses from China), (ii) SARS-CoV-2 related coronaviruses (SCoV2rC; including five bat viruses from Cambodia, Thailand and Yunnan), (iii) pangolin sarbecoviruses, (iv) three bat sarbecoviruses showing evidence of recombination between SCoVrC and SCoV2rC genomes, (v) two highly divergent bat sarbecoviruses from Yunnan, (vi) the bat sarbecovirus from Japan, (vii) the bat sarbecovirus from Bulgaria, and (viii) the bat sarbecovirus from Kenya. All these groups can be diagnosed by specific nucleotide compositional features except the one concerned by recombination between SCoVrC and SCoV2rC. In particular, SCoV2rC genomes have less cytosines and more uracils at third codon-positions than other sarbecoviruses, whereas the genomes of pangolin sarbecoviruses show more adenines at third codon-positions. I suggest that taxonomic differences in the imbalanced nucleotide pools available in host cells during viral replication can explain the eight groups of SNC here detected among Sarbecovirus genomes. A related effect due to hibernating bats and their latitudinal distribution is also discussed. I conclude that the two independent host switches from Rhinolophus bats to pangolins resulted in convergent mutational constraints and that SARS-CoV-2 emerged directly from a horseshoe bat sarbecovirus.

A Look inside the Replication Dynamics of SARS-CoV-2 in Blyth's Horseshoe Bat (Rhinolophus lepidus) Kidney Cells.

ABSTRACTBats are considered the natural reservoir of numerous emerging viruses such as severe acute respiratory syndrome coronaviruses (SARS-CoVs). There is a need for immortalized bat cell lines to culture and investigate the pathogenicity, replication kinetics, and evolution of emerging coronaviruses. We illustrate the susceptibility and permissiveness of a spontaneously immortalized kidney cell line (Rhileki) from Blyth’s horseshoe bat (R. lepidus) to SARS-CoV-2 virus, including clinical isolates, suggesting a possible virus-host relationship. We were able to observe limited SARS-CoV-2 replication in Rhileki cells compared with simian VeroE6 cells. Slower viral replication in Rhileki cells was indicated by higher ct values (RT-PCR) at later time points of the viral culture and smaller foci (foci forming assay) compared with those of VeroE6 cells. With this study we demonstrate that SARS-CoV-2 replication is not restricted to R. sinicus and could include more Rhinolophus species. The establishment of a continuous Rhinolophus lepidus kidney cell line allows further characterization of SARS-CoV-2 replication in Rhinolophus bat cells, as well as isolation attempts of other bat-borne viruses.IMPORTANCE The current COVID-19 pandemic demonstrates the significance of bats as reservoirs for severe viral diseases. However, as bats are difficult to establish as animal models, bat cell lines can be an important proxy for the investigation of bat-virus interactions and the isolation of bat-borne viruses. This study demonstrates the susceptibility and permissiveness of a continuous kidney bat cell line to SARS-CoV-2. This does not implicate the bat species Rhinolophus lepidus, where these cells originate from, as a potential reservoir, but emphasizes the usefulness of this cell line for further characterization of SARS-CoV-2. This can lead to a better understanding of emerging viruses that could cause significant disease in humans and domestic animals.

Genomic determinants of Furin cleavage in diverse European SARS-related bat coronaviruses

The furin cleavage site (FCS) in SARS-CoV-2 is unique within the Severe acute respiratory syndrome–related coronavirus (SrC) species. We re-assessed diverse SrC from European horseshoe bats and analyzed the spike-encoding genomic region harboring the FCS in SARS-CoV-2. We reveal molecular features in SrC such as purine richness and RNA secondary structures that resemble those required for FCS acquisition in avian influenza viruses. We discuss the potential acquisition of FCS through molecular mechanisms such as nucleotide substitution, insertion, or recombination, and show that a single nucleotide exchange in two European bat-associated SrC may suffice to enable furin cleavage. Furthermore, we show that FCS occurrence is variable in bat- and rodent-borne counterparts of human coronaviruses. Our results suggest that furin cleavage sites can be acquired in SrC via conserved molecular mechanisms known in other reservoir-bound RNA viruses and thus support a natural origin of SARS-CoV-2.

Rediscovery of the critically endangered Hill's horseshoe bat (Rhinolophushilli) and other new records of bat species in Rwanda.

For forty years, there has been growing uncertainty about whether Hill's horseshoe bat (Rhinolophushilli) still persists in Nyungwe National Park, Rwanda. Only known from one small area within the National Park, R.hilli is listed as Critically Endangered by the International Union for the Conservation of Nature (IUCN), based on its extremely small geographic range and presumed low number of mature individuals. Here, we present and describe bat species occurrence data contributed to the Global Biodiversity Information Facility (GBIF) that we collected as part of a long-term collaborative project to rediscover this lost species. This data paper describes the survey methods and findings resulting from cave roost surveys, capture surveys, and acoustic sampling of bat echolocation activity in Nyungwe National Park and surrounding areas in south-western Rwanda from 2013-2020 and their conservation relevance. We report the discovery of an extant population of Hill's horseshoe bat (Rhinolophushilli) in Nyungwe National Park, Rwanda, 40 years since the last reported observation of the species in 1981. We also report the first record of Lander's horseshoe bat (Rhinolophuslanderi) in Nyungwe National Park and the first record of the Damara woolly bat (Kerivoulaargentata) in Rwanda. The dataset contributed to GBIF and described in this paper includes 278 occurrence records from 10 bat species of five families detected at 71 locations in or near Nyungwe National Park, Rwanda. We include a description of the morphological descriptions of R.hilli and present the first acoustic echolocation signatures and phylogenetic information for this species.

COVID-19 Vaccines and the Efficacy of Currently Available Vaccines Against COVID-19 Variants.

Severe acute respiratory syndrome coronavirus 2 is the seventh member of the Coronaviridiae family of viruses, which are thought to be transmitted by Chinese horseshoe bats. The virus undergoes mutations leading to variants such as B.1.1.7 (alpha), B.1.351 (beta), P.1 (gamma), and B.1.617 (delta), as well as the recent variant B.1.1.529 (omicron), which has around 30 deletions, making it a severely mutated form that lowers vaccination-induced protection. Vaccine efficacy is usually expressed as relative risk reduction, which is based on the ratio of attack rates with and without a vaccine, whereas absolute risk reduction is based on the entire population. Rather than two doses, recent research suggests that a third dose/booster dose may aid in protection against future variants. The constant influx of mutant variations is putting a strain on vaccine production. Despite the challenges, we are optimistic that the epidemic will be eradicated by achieving mass immunity and by ensuring that everyone receives vaccines at a faster rate.

Impacts of seasonality on gene expression in the Chinese horseshoe bat.

Seasonality can cause changes in many environmental factors which potentially affects gene expression. Here, we used a bat species (Rhinolophus sinicus) from eastern China as a model to explore the molecular mechanisms of seasonal effects, in particular during phenological shifts in the spring and autumn. Based on the analysis of 45 RNA‐seq samples, we found strong seasonal effects on gene expression, with a large number of genes identified as either specific or biased to each season. Weighted gene co‐expression network analysis also identified multiple modules significantly associated with each season. These seasonal genes were further enriched into different functional categories. Consistent with effects of phenological shifts on bats, we found that genes related to promoting food intake were highly expressed in both autumn and spring. In addition, immunity genes were also highly expressed in both seasons although this seasonal immune response had tissue specificity in different seasons. In female bats, genes related to the delay of ovulation (e.g., NPPC, natriuretic peptide precursor type C) were highly expressed in October, while genes associated with the promotion of reproduction (e.g., DIO2, iodothyronine deiodinase 2) were biasedly expressed in April. Lastly, we found multiple known core clock genes in both October‐biased and April‐biased expressed genes, which may be involved in regulating the start and end of hibernation, respectively. Overall, together with studies in other land and aquatic animals, our work supports that seasonal gene expression variations may be a general evolutionary response to environmental changes in wild animals.

Resting Frequency of Echolocation Calls within a Lesser Horseshoe Bat Population (Southern Poland) and its Relation to Body Size, Condition and Mass

The echolocation calls emitted by stationary bats are characterised by their resting frequency (RF). The ecological role of RF has been widely discussed across the literature concerning the Rhinolophidae family, where it has been found that the RF may vary depending on many factors, although its role in shaping the variability of different populations remains unclear, and the data for many species – includingRhinolophus hipposideros– is scarce. In this study, we aimed to determine how sex, age and biometric parameters (body mass, forearm length and the body condition index) affected the RF in aR. hipposiderospopulation and to investigate the individual variability in this parameter. Bats were captured in front of two Carpathian caves in Southern Poland during the mating season. The echolocation calls of the hand-held bats were recorded, and later their peak frequency was measured with computer software. The analyses showed higher RF values for females than for males, but (in contrast to previous reports) no differences between the age classes were identified. RF did not correlate with any biometric parameters in the studied population, which rules out the possibility of quality characteristic signalling through this parameter. However, we observed significant individual differences in RF within the sex-age groups, which might reflect some communication potential. The discrepancies among the research results available for this topic indicate the need for further studies aimed at investigating the variability of RF and its role across species distribution ranges and their phenology.

Epidemiology and Genomic Characterization of Two Novel SARS-Related Coronaviruses in Horseshoe Bats from Guangdong, China.

ABSTRACTSevere acute respiratory syndrome (SARS) coronavirus (SARS-CoV) and SARS-CoV-2, the causative agents of SARS, which broke out in 2003, and coronavirus disease 2019 (COVID-2019), which broke out in 2019, probably originated in Rhinolophus sinicus and R. affinis, respectively. Rhinolophus bats are important hosts for coronaviruses. Many SARS-related coronaviruses (SARSr-CoVs) have been detected in bats from different areas of China; however, the diversity of bat SARSr-CoVs is increasing, and their transmission mechanisms have attracted much attention. Here, we report the findings of SARSr-CoVs in R. sinicus and R. affinis from South China from 2008 to 2021. The full-length genome sequences of the two novel SARSr-CoVs obtained from Guangdong shared 83 to 88% and 71 to 72% nucleotide identities with human SARS-CoV and SARS-CoV-2, respectively, while sharing high similarity with human SARS-CoV in hypervariable open reading frame 8 (ORF8). Significant recombination occurred between the two novel SARSr-CoVs. Phylogenetic analysis showed that the two novel bat SARSr-CoVs from Guangdong were more distant than the bat SARSr-CoVs from Yunnan to human SARS-CoV. We found that transmission in bats contributes more to virus diversity than time. Although our results of the sequence analysis of the receptor-binding motif (RBM) and the expression pattern of angiotensin-converting enzyme 2 (ACE2) inferred that these viruses could not directly infect humans, risks still exist after some unpredictable mutations. Thus, this study increased our understanding of the genetic diversity and transmission of SARSr-CoVs carried by bats in the field.

Social networks of the greater horseshoe bat during the hibernation season: a landscape-scale case study

Bats are highly social animals, and the interactions between individuals are likely to be important to their ecology and conservation. Social structures are affected by the physical environment (spatial factors), as well as varying over time and seasons (temporal factors). Compared with many other taxa, individual bats are capable of moving large distances, so experience a range of spatial locations. They have long life spans, providing opportunities to interact with others over a long period, and are often highly gregarious. Using a long-term data set, we examined the social behaviour, along with spatial and temporal influences, of greater horseshoe bats, Rhinolophus ferrumequinum , during hibernation using social network approaches. Across 17 years, 2808 individuals were monitored, yielding a total of 5952 records at 21 roost locations. We investigated how individuals’ life history traits (sex, age and breeding status of females) and the frequency of observation affected social associations and identified factors that influenced the movement of individuals between locations. Older and male animals were significantly more central in the social network, and adult males may act as a link between socially separate individuals within the society. The social network had high nonrandom dyadic structuring, with assortment by age stronger in females than males, and this was likely to be influenced by spatiotemporal factors. In general, higher weighted betweenness scores were recorded in a noncore hibernaculum, suggesting that these sites, despite low numbers of bats being present, may act as locations to connect less-connected individuals, as well as communities. Finally, movements between hibernacula were only associated with the frequency of observation rather than any life history trait. These results illustrate the interconnectivity across sites, stressing the need for appropriate cross-jurisdiction species management plans to be created for species that utilize and move between multiple sites within the landscape. • Older and male bats are more central in social networks during hibernation. • Assortment by age is stronger in female bats compared to males. • Assortment is likely to be influenced by spatiotemporal factors. • Movement between hibernation sites was only affected by frequency of observation.

Bats (Mammalia, Chiroptera) from a cave area in NW Italy

Caves play an important role in bat ecology, offering natural roosting and wintering sites. In the reproductive period, bats need to find an effective foraging environment away from the cave entrance, but only few studies have considered the use of foraging habitats in the immediate proximity of the caves. We provide a list of 18 bat species and 5 bat acoustic groups observed in a system of 81 caves in NW Italy. Winter censuses carried out during 17 years showed an increase of the Greater Horseshoe bat, a species of conservation concern. In the summer period this rare species was also observed foraging in nearby areas. Recording of bat calls in the summer period was performed both at cave entrances and in three foraging habitats present in the area surrounding the cave (woods, agricultural mosaic with artificial light, dark mosaic). Light mosaics and woods showed the highest foraging activity (160.3 and 72.0 pass/hour), while woods and cave entrances were accessed by the largest number of bat species. Our survey improves the inventory of bat species in a poorly sampled area, and we recommend a reduced tourism access, thereby promoting preservation of bats.

Facial muscle modification associated with chiropteran noseleaf development: Insights into the developmental basis of a movable rostral appendage in mammals.

Mammal evolution has generated diverse craniofacial morphologies, including remarkable movable rostral appendages. However, the muscular and skeletal architecture providing the mobility of these appendages remains largely unexplored. Here, we focus on chiropteran noseleaves and compare the three-dimensional internal morphology of late-stage embryos between the greater horseshoe bat Rhinolophus ferrumequinum, which possesses a noseleaf, and the Asian bent-winged bat Miniopterus fuliginosus and Egyptian fruit bat Rousettus aegyptiacus, which do not. We also assess earlier stage cell proliferation within the rostrum to elucidate cellular mechanisms underlying noseleaf-associated morphological modifications. The musculus maxillolabialis inserted into proximal vibrissae follicles in M fuliginosus and R aegyptiacus embryos but instead inserted into the horseshoe plate in R ferrumequinum. This modification suggests that the M maxillolabialis has adapted to controlling the noseleaf rather than vibrissae in rhinolophid bats. Our cellular analysis showed higher cell proliferation within the maxillary and frontonasal processes of St. 14 embryos in R ferrumequinum compared to M fuliginosus and R aegyptiacus, suggesting that the spatial alteration of noseleaf-associated muscle is derived from changes in facial morphogenesis that occur by St. 14. This is the first study clarifying the morphological and cellular bases underlying the development of mammalian rostral appendages.

Thus spoke peptides: SARS-CoV-2 spike gene evolved in humans and then shortly in rats while the rest of its genome in horseshoe bats and then in treeshrews

ABSTRACT SARS-CoV-2 is suspected to be the product of a natural or artificial recombination of two viruses – one adapted to the horseshoe bat and the other, donor of the spike protein gene, adapted to an unknown species. Here we used a new method to search for the original host of the ancestor of the SARS-CoV-2 virus and for the donor of its gene for the spike protein, the molecule responsible for binding to and entering human cells. We computed immunological T-distances (the number of different peptides that are present in the viral proteins but absent in proteins of the host) between 11 species of coronaviruses and 38 representatives of the main mammal clades. Analyses of pentapeptides, the presumed principal targets of T-cell non-self recognition, showed the smallest T-distance of the spike protein of SARS-CoV-2 to humans, while the rest of SARS-CoV-2 proteome to the horseshoe bat. This suggests that the ancestor of SARS-CoV-2 was adapted to bats, but the spike gene donor was adapted to humans. Further analyses suggest that the ancestral coronavirus adapted to bats was shortly passaged in treeshrews, while the donor of the spike gene was shortly passaged in rats before the recombination event.

Paramyxovirus Diversity within One Population of Miniopterus fuliginosus Bats in Sri Lanka.

Bats are known as typical reservoirs for a number of viruses, including viruses of the family Paramyxoviridae. Representatives of the subfamily Orthoparamyxovirinae are distributed worldwide and can cause mild to fatal diseases when infecting humans. The research on Paramyxoviruses (PMVs) from different bat hosts all over the world aims to understand the diversity, evolution and distribution of these viruses and to assess their zoonotic potential. A high number of yet unclassified PMVs from bats are recorded. In our study, we investigated bat species from the families Rhinolophidae, Hipposiderae, Pteropodidae and Miniopteridae that are roosting sympatrically in the Wavul Galge cave (Koslanda, Sri Lanka). The sampling at three time points (March and July 2018; January 2019) and screening for PMVs with a generic PCR show the presence of different novel PMVs in 10 urine samples collected from Miniopterus fuliginosus. Sequence analysis revealed a high similarity of the novel strains among each other and to other unclassified PMVs collected from Miniopterus bats. In this study, we present the first detection of PMVs in Sri Lanka and the presence of PMVs in the bat species M. fuliginosus for the first time.

Horseshoe bats use not changes in echo delay but Doppler shift to perceive approaching objects

Echolocating bats use echo delay for target ranging and Doppler shift information for relative velocity recognition. However, how they perceive moving objects remains unclear. To investigate this question, we played back echolocation pulses in real-time as virtual echoes to Japanese horseshoe bats (Rhinolophus ferrumequinum nippon) on a perch in a flight room. Since echoes coming back from an approaching object are theoretically characterized by both changes in echo delay and the presence of Doppler shift, we reproduced an artificial approaching object by encoding these two acoustic parameters in the virtual echoes. As a result, only Doppler shift evoked bats flight reaction, showing that they use only Doppler shift and not change in echo delay to perceive approaching objects. Also, we played back only constant frequency (CF) component and confirmed that they use the CF component to detect Doppler shift. Furthermore, as a response to the Doppler shift in the perceived echo, bats increased the bandwidth of the terminal component of their pulse. Surprisingly, this response occurred in the very first pulse after Doppler shift, which indicates bats can adapt their echolocation pulse characteristics to changing situations within a pulse. [This work was supported by JSPS KAKENHI Grant Nos. 18H03786 and 16H06542.]

How to Accurately Delineate Morphologically Conserved Taxa and Diagnose Their Phenotypic Disparities: Species Delimitation in Cryptic Rhinolophidae (Chiroptera)

Systematics and taxonomy are the backbone of all components of biology and ecology, yet cryptic species present a major challenge for accurate species identification. This is especially problematic as they represent a substantial portion of undiscovered biodiversity, and have implications for not only species conservation, but even assaying potential risk of zoonotic spillover. Here, we use integrative approaches to delineate potential cryptic species in horseshoe bats (Rhinolophidae), evaluate the phenotypic disparities between cryptic species, and identify key traits for their identification. We tested the use of multispecies coalescent models (MSC) using Bayesian Phylogenetic and Phylogeography (BPP) and found that BPP was useful in delineating potential cryptic species, and consistent with acoustic traits. Our results show that around 40% of Asian rhinolophid species are potentially cryptic and have not been formally described. In order to avoid potential misidentification and allow species to be accurately identified, we identified quantitative noseleaf sella and acoustic characters as the most informative traits in delineating between potential cryptic species in Rhinolophidae. This highlights the physical differences between cryptic species that are apparent in noseleaf traits which often only qualitatively described but rarely measured. Each part of the noseleaf including the sella, lateral lappets, and lancet furrows, play roles in focusing acoustic beams and thus, provide useful characteristics to identify cryptic Rhinolophus species. Finally, species delimitation for cryptic species cannot rely on genetic data alone, but such data should be complemented by other evidence, including phenotypic, acoustic data, and geographic distributions to ensure accurate species identification and delineation.

Systematic Tracing of Susceptible Animals to SARS-CoV-2 by a Bioinformatics Framework.

Since the outbreak of SARS-CoV-2 in 2019, the Chinese horseshoe bats were considered as a potential original host of SARS-CoV-2. In addition, cats, tigers, lions, mints, and ferrets were naturally or experimentally infected with SARS-CoV-2. For the surveillance and control of this highly infectious disease, it is critical to trace susceptible animals and predict the consequence of potential mutations at the binding region of viral spike protein and host ACE2 protein. This study proposed a novel bioinformatics framework to systematically trace susceptible animals to SARS-CoV-2 and predict the binding affinity between susceptible animals’ mutated/un-mutated ACE2 receptors. As a result, we identified a few animals posing a potential risk of infection with SARS-CoV-2 using the docking analysis of ACE2 protein and viral spike protein. The binding affinity of some of these species is weaker than that of humans but more potent than that of Chinese horseshoe bats. We also found that a few point mutations in human ACE2 protein or viral spike protein could significantly enhance their binding affinity, posing an enormous potential threat to public health. The ancestors of the Omicron may evolve rapidly through the accumulation of mutations in infecting the host and jumped into human beings. These findings indicate that if the epidemic expands, there may be a human-animal-human transmission route, which will increase the difficulty of disease prevention and control.

COVID19, ENVIRONMENT, CLINICOPATHOLOGIC FEATURES, LABORATORY FINDINGS AND DIAGNOSIS, TREATMENT, VACCINES, ANIMALS, AND CANCER

SARS-CoV-2 (COVID-19) belongs to the same coronavirus group (Beta-coronavirus) as SARS and MERS viruses that caused two of the more severe epidemics in recent years. Horseshoe bats (genus Rhinolophus) have been identified as the natural reservoirs of SARS-related coronaviruses (CoVs) and the likely origin of SARS-CoV-2. The intermediate host is thought to be the pangolin. … Continued