We identified seven distinct coronaviruses (CoVs) in bats from Brazil, classified into 229E-related (Alpha-CoV), Nobecovirus, Sarbecovirus, and Merbecovirus (Beta-CoV), including one closely related to MERS-like CoV with 82.8% genome coverage. To accomplish this, we screened 423 oral and rectal swabs from 16 different bat species using molecular assays, RNA sequencing, and evolutionary analysis. Notably, gaps in the spike-encoding gene led us to design new primers and perform Sanger sequencing, which revealed high similarities to MERS-related (MERSr) CoV strains found in humans and camels. Additionally, we identified key residues in the receptor-binding domain (RBD) of the spike protein, suggesting potential interactions with DPP4, the receptor for MERSr-CoV. Our analyses also revealed evidence of recombination involving our laboratory-produced sequences. These findings highlight the extensive genetic diversity of CoVs, the presence of novel viral lineages, and the occurrence of recombination events among bat CoVs circulating in Brazil, underscoring the critical role bats play as reservoirs for emerging viruses and emphasizing the necessity of ongoing surveillance to monitor the public health risks associated with CoV spillover events.
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http://dx.doi.org/10.1002/jmv.70173 | DOI Listing |
J Med Virol
January 2025
Department of Morphology and Genetics, Federal University of São Paulo, São Paulo-SP, Brazil.
We identified seven distinct coronaviruses (CoVs) in bats from Brazil, classified into 229E-related (Alpha-CoV), Nobecovirus, Sarbecovirus, and Merbecovirus (Beta-CoV), including one closely related to MERS-like CoV with 82.8% genome coverage. To accomplish this, we screened 423 oral and rectal swabs from 16 different bat species using molecular assays, RNA sequencing, and evolutionary analysis.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
The emergence of SARS-CoV-2 variants of concern (VOCs) has greatly diminished the neutralizing activity of previously FDA-approved monoclonal antibodies (mAbs), including that of antibody cocktails and of first-generation broadly neutralizing antibodies such as S309 (Sotrovimab). In contrast, antibodies targeting cryptic conformational epitopes of the receptor binding domain (RBD) have demonstrated broad activity against emerging variants, but exert only moderate neutralizing activity, which has so far hindered clinical development. Here, we utilize in vitro display technology to identify and affinity-mature antibodies targeting the cryptic class 6 epitope, accessible only in the "up" conformation of the SARS-CoV-2 spike trimer.
View Article and Find Full Text PDFVirol J
December 2024
Department of Molecular and Translational Medicine, Section of Microbiology, University of Brescia, Piazzale Spedali Civili, 1, Brescia, 25123, Italy.
Background: Since the beginning of the pandemic, contact tracing has been one of the most relevant issues to understand SARS-CoV-2 transmission dynamics and, in this context, the analysis of quasispecies may turn out to be a useful tool for outbreak investigations. Analysis of the intra-host single nucleotide variants (iSNVs) found in the nsp2, ORF3, and ORF7 genes of SARS-CoV-2 was conducted in order to correctly identify virus transmission chain among patients hospitalized in Brescia Civic Hospital.
Methods: During the period between August and October 2023, 13 nasopharyngeal specimens, collected from patients admitted to Brescia Civic Hospital, were tested for SARS-CoV-2 positivity and molecularly characterized.
Nat Commun
December 2024
Engineering Biology Research Center, Kobe University, Kobe, Japan.
Inducible promoters are essential for precise control of target gene expression in synthetic biological systems. However, engineering eukaryotic promoters is often more challenging than engineering prokaryotic promoters due to their greater mechanistic complexity. In this study, we describe a simple and reliable approach for constructing strongly inducible synthetic promoters with minimum leakiness in yeasts.
View Article and Find Full Text PDFCurr Biol
December 2024
Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, USA; Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, MD 20815, USA. Electronic address:
Coronaviruses exhibit many mechanisms of genetic innovation, including the acquisition of accessory genes that originate by capture of cellular genes or through duplication of existing viral genes. Accessory genes influence viral host range and cellular tropism, but little is known about how selection acts on these variable regions of virus genomes. We used experimental evolution of mouse hepatitis virus (MHV) encoding a cellular AKAP7 phosphodiesterase and an inactive native phosphodiesterase, NS2, to model the evolutionary fate of accessory genes.
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