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Cross-species transmission of viruses from wildlife animal reservoirs poses a marked threat to human and animal health 1 . Bats have been recognized as one of the most important reservoirs for emerging viruses and the transmission of a coronavirus that originated in bats to humans via intermediate hosts was responsible for the high-impact emerging zoonosis, severe acute respiratory syndrome (SARS) 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 – 10 . Here we provide virological, epidemiological, evolutionary and experimental evidence that a novel HKU2-related bat coronavirus, swine acute diarrhoea syndrome coronavirus (SADS-CoV), is the aetiological agent that was responsible for a large-scale outbreak of fatal disease in pigs in China that has caused the death of 24,693 piglets across four farms. Notably, the outbreak began in Guangdong province in the vicinity of the origin of the SARS pandemic. Furthermore, we identified SADS-related CoVs with 96–98% sequence identity in 9.8% (58 out of 591) of anal swabs collected from bats in Guangdong province during 2013–2016, predominantly in horseshoe bats ( Rhinolophus spp.) that are known reservoirs of SARS-related CoVs. We found that there were striking similarities between the SADS and SARS outbreaks in geographical, temporal, ecological and aetiological settings. This study highlights the importance of identifying coronavirus diversity and distribution in bats to mitigate future outbreaks that could threaten livestock, public health and economic growth. Analysis of viral samples from deceased piglets shows that a bat coronavirus was responsible for an outbreak of fatal disease in China and highlights the importance of the identification of coronavirus diversity and distribution in bats in order to mitigate future outbreaks of disease.

Zoonotic coronaviruses represent an ongoing threat, yet the myriads of circulating animal viruses complicate the identification of higher-risk isolates that threaten human health. Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a newly discovered, highly pathogenic virus that likely evolved from closely related HKU2 bat coronaviruses, circulating in Rhinolophus spp. bats in China and elsewhere. As coronaviruses cause severe economic losses in the pork industry and swine are key intermediate hosts of human disease outbreaks, we synthetically resurrected a recombinant virus (rSADS-CoV) as well as a derivative encoding tomato red fluorescent protein (tRFP) in place of ORF3. rSADS-CoV replicated efficiently in a variety of continuous animal and primate cell lines, including human liver and rectal carcinoma cell lines. Of concern, rSADS-CoV also replicated efficiently in several different primary human lung cell types, as well as primary human intestinal cells. rSADS-CoV did not use human coronavirus ACE-2, DPP4, or CD13 receptors for docking and entry. Contemporary human donor sera neutralized the group I human coronavirus NL63, but not rSADS-CoV, suggesting limited human group I coronavirus cross protective herd immunity. Importantly, remdesivir, a broad-spectrum nucleoside analog that is effective against other group 1 and 2 coronaviruses, efficiently blocked rSADS-CoV replication in vitro. rSADS-CoV demonstrated little, if any, replicative capacity in either immune-competent or immunodeficient mice, indicating a critical need for improved animal models. Efficient growth in primary human lung and intestinal cells implicate SADS-CoV as a potential higher-risk emerging coronavirus pathogen that could negatively impact the global economy and human health.

Wild mammalian species, including bats, constitute the natural reservoir of betacoronavirus (including SARS, MERS, and the deadly SARS-CoV-2). Different hosts or host tissues provide different cellular environments, especially different antiviral and RNA modification activities that can alter RNA modification signatures observed in the viral RNA genome. The zinc finger antiviral protein (ZAP) binds specifically to CpG dinucleotides and recruits other proteins to degrade a variety of viral RNA genomes. Many mammalian RNA viruses have evolved CpG deficiency. Increasing CpG dinucleotides in these low-CpG viral genomes in the presence of ZAP consistently leads to decreased viral replication and virulence. Because ZAP exhibits tissue-specific expression, viruses infecting different tissues are expected to have different CpG signatures, suggesting a means to identify viral tissue-switching events. The author shows that SARS-CoV-2 has the most extreme CpG deficiency in all known betacoronavirus genomes. This suggests that SARS-CoV-2 may have evolved in a new host (or new host tissue) with high ZAP expression. A survey of CpG deficiency in viral genomes identified a virulent canine coronavirus (alphacoronavirus) as possessing the most extreme CpG deficiency, comparable with that observed in SARS-CoV-2. This suggests that the canine tissue infected by the canine coronavirus may provide a cellular environment strongly selecting against CpG. Thus, viral surveys focused on decreasing CpG in viral RNA genomes may provide important clues about the selective environments and viral defenses in the original hosts.

The Coronavirus Disease 2019 (COVID-19) is a new viral infection caused by the severe acute respiratory coronavirus 2 (SARS-CoV-2). Genomic analyses have revealed that SARS-CoV-2 is related to Pangolin and Bat coronaviruses. In this report, a structural comparison between the Sars-CoV-2 Envelope and Membrane proteins from different human isolates with homologous proteins from closely related viruses is described. The analyses here reported show the high structural similarity of Envelope and Membrane proteins to the counterparts from Pangolin and Bat coronavirus isolates. However, the comparisons have also highlighted structural differences specific of Sars-CoV-2 proteins which may be correlated to the cross-species transmission and/or to the properties of the virus. Structural modelling has been applied to map the variant sites onto the predicted three-dimensional structure of the Envelope and Membrane proteins.

Bats are flying mammals distributed worldwide known to host several types of Coronavirus (CoV). Since they were reported as the probable source of spillover of highly pathogenic CoV into the human population, investigating the circulation of this virus in bats around the world became of great importance. We analyzed samples from 103 bats from two distinct regions in Brazil. Coronavirus from the Alphacoronavirus genus was detected in 12 animals, 11 from São José do Rio Preto—SP region and 1 from Barreiras—BA region, resulting in a prevalence of 17.18% and 2.56% respectively. The virus was detected not only in intestines but also in lungs and liver. Phylogenetic analysis based on nsP12 genomic region suggests that the sequences group according to host family and sampling location. Studies on the circulation of these viruses in bats remain important to understand the ecology and evolutionary relationship of these pathogens.

Background Members of the species Alphacoronavirus suis/Alphacoronavirus-1 ( αCoV-1 ) are important viral pathogens of canids/felids that exhibit complex evolutionary patterns and have been associated with interspecies transmission events including zoonoses. Mongooses (family Herpestidae , order Carnivora ) are scavengers that pose a risk as potential carrier of viral pathogens. To date, there are no reports on the genetic make-up/diversity of CoVs circulating in mongoose populations. Methods Fecal samples obtained from 53 small Indian mongooses ( Urva auropunctata ) on the Caribbean island of St. Kitts were screened for CoVs using a pan -CoV RT-semi-nested PCR assay and canine αCoV-specific RT-PCR assays. The partial RNA-dependent RNA polymerase (RdRp) and membrane protein (M) coding sequences (CDS) and the nearly full-length spike (S) protein CDS were determined from the mongoose CoVs and analyzed in the present study. Results We report here high detection rates of αCoVs (30.18%, 16/53 samples) in small Indian mongooses on St. Kitts, indicating that αCoVs might be widely circulating in the island mongoose population. Analysis of the CoV RdRp-, M- and S- CDS revealed significant genetic diversity among the mongoose CoVs, and between mongoose CoVs and other αCoVs, including evidence for at least 2 recombination events (involving S gene), one of which involved the putative receptor binding domain (RBD). Phylogenetically, the mongoose CoVs formed distinct cluster/s within the canine CoV-2 (CCoV-2) lineage and appeared to be more related to CCoV-2b than other αCoVs. Despite differences in the S CDS including those in the RBD, the mongoose CoVs preserved certain features that are characteristic of CCoV-2 (lack of furin cleavage motif at S1/S2 site and presence of cleavage motif at S2’ site) and retained the crucial amino acid residues essential for αCoV binding to the host aminopeptidase N receptor. Conclusions The present study is the first to report high detection rates and genetic makeup/diversity of CoVs in mongooses, expanding our knowledge on the host range and complex evolutionary patterns of αCoVs. Considering our findings, the proximity of mongoose to other canids/felids and humans, and cross-species transmission potential of CoVs, large-scale studies on prevalence and genetic diversity of CoVs that might be circulating in different mongoose species/populations, and in-depth investigation of mongoose CoV RBD-host receptor interactions are of utmost importance.

Bats are the reservoir or ancestral hosts of important emerging coronaviruses affecting people (e.g., SARS-CoV and SARS-CoV-2) and livestock (e.g., PEDV, SADS-CoV). Here, we analyzed 523 genetic sequences of SADS-CoV that caused large-scale die-offs of pigs in China, which is known to be able to infect human cells and related HKU2-CoVs. We used this information to identify the horseshoe bat Rhinolophus affinis as the likely spillover host for the outbreak in pigs, and identified the bat species within which these viruses evolved. We then modeled the distribution of these host species and their overlap with dense human and pig populations to identify the regions where surveillance programs can help identify spillover events and prevent future outbreaks.

Swine acute diarrhoea syndrome coronavirus (SADS-CoV; Coronaviridae, Rhinacovirus) was detected in 2017 in Guangdong Province (China), where it caused high mortality rates in piglets. According to previous studies, SADS-CoV evolved from horseshoe bat reservoirs. Here, we report the first five Rhinacovirus genomes sequenced in horseshoe bats from Vietnam and their comparisons with data published in China. Our phylogenetic analyses provided evidence for four groups: rhinacoviruses from Rhinolphus pusillus bats, including one from Vietnam; bat rhinacoviruses from Hainan; bat rhinacoviruses from Yunnan showing a divergent synonymous nucleotide composition; and SADS-CoV and related bat viruses, including four rhinacoviruses from Vietnam sampled in Rhinolophus affinis and Rhinolophus thomasi. Our phylogeographic analyses showed that bat rhinacoviruses from Dien Bien (Vietnam) share more affinities with those from Yunnan (China) and that the ancestor of SADS-CoVs arose in Rhinolophus affinis circulating in Guangdong. We detected sequencing errors and artificial chimeric genomes in published data. The two SADS-CoV genomes previously identified as recombinant could also be problematic. The reliable data currently available, therefore, suggests that all SADS-CoV strains originate from a single bat source and that the virus has been spreading in pig farms in several provinces of China for at least seven years since the first outbreak in August 2016.

Bats are presumed reservoirs of diverse coronaviruses (CoVs) including progenitors of Severe Acute Respiratory Syndrome (SARS)-CoV and SARS-CoV-2, the causative agent of COVID-19. However, the evolution and diversification of these coronaviruses remains poorly understood. Here we use a Bayesian statistical framework and a large sequence data set from bat-CoVs (including 589 novel CoV sequences) in China to study their macroevolution, cross-species transmission and dispersal. We find that host-switching occurs more frequently and across more distantly related host taxa in alpha- than beta-CoVs, and is more highly constrained by phylogenetic distance for beta-CoVs. We show that inter-family and -genus switching is most common in Rhinolophidae and the genus Rhinolophus . Our analyses identify the host taxa and geographic regions that define hotspots of CoV evolutionary diversity in China that could help target bat-CoV discovery for proactive zoonotic disease surveillance. Finally, we present a phylogenetic analysis suggesting a likely origin for SARS-CoV-2 in Rhinolophus spp. bats. Bats are a likely reservoir of zoonotic coronaviruses (CoVs). Here, analyzing bat CoV sequences in China, the authors find that alpha-CoVs have switched hosts more frequently than betaCoVs, identify a bat family and genus that are highly involved in host-switching, and define hotspots of CoV evolutionary diversity.

Bats are associated with some of the most significant and virulent emerging zoonoses globally, yet research and surveillance of bat pathogens remains limited across parts of the world. We surveyed the prevalence and genetic diversity of coronaviruses from bats in Taita Hills, southeastern Kenya, as part of ongoing surveillance efforts in this remote part of eastern Africa. We collected fecal and intestinal samples in May 2018 and March 2019 from 16 bat species. We detected one genus of coronavirus (alphacoronavirus), with an overall RNA prevalence of 6.5% (30/463). The prevalence of coronavirus RNA was 3.8% (9/235) and 11.6% (21/181) for the two most captured free-tailed bat species, Mops condylurus and M. pumilus respectively, with no detections from other bat species (0/90). Phylogenetic analyses based on the partial RNA-dependent RNA polymerase gene and whole genome sequences revealed that the sequences clustered together and were closely related to alphacoronavirus detected in free tailed bats in Eswatini, Nigeria and Rhinolophus simulator bats in South Africa. The sequences were more distantly related to alphacoronavirus isolated from Chaerophon plicatus bat species in Yunnan province, China and Ozimops species from southwestern Australia. These findings highlight coronavirus transmission among bats that share habitats with humans and livestock, posing a potential risk of exposure. Future research should investigate whether coronaviruses detected in these bats have the potential to spillover to other hosts.