Brazil currently has one of the fastest growing SARS-CoV-2 epidemics in the world. Owing to limited available data, assessments of the impact of non-pharmaceutical interventions (NPIs) on virus spread remain challenging. Using a mobility-driven transmission model, we show that NPIs reduced the reproduction number from >3 to 1–1.6 in São Paulo and Rio de Janeiro. Sequencing of 427 new genomes and analysis of a geographically representative genomic dataset identified >100 international virus introductions in Brazil. We estimate that most (76%) of the Brazilian strains fell in three clades that were introduced from Europe between 22 February11 March 2020. During the early epidemic phase, we found that SARS-CoV-2 spread mostly locally and within-state borders. After this period, despite sharp decreases in air travel, we estimated multiple exportations from large urban centers that coincided with a 25% increase in average travelled distances in national flights. This study sheds new light on the epidemic transmission and evolutionary trajectories of SARS-CoV-2 lineages in Brazil, and provide evidence that current interventions remain insufficient to keep virus transmission under control in the country.

Problem drug use and dependence are neurobehavioral disorders of complex origin. Although environmental factors contribute to drug abuse and addiction, genetic factors also play a significant role estimated at 40 -60% of the total risk. Nonetheless, the precise identities of human genes that confer vulnerability to problem drug use remain mostly unknown. Here, we describe a natural single nucleotide polymorphism in the human gene that encodes the principal endocannabinoid-inactivating enzyme, fatty acid amide hydrolase (FAAH), that in homozygous form is strongly associated with both street drug use and problem drug͞alcohol use. This single nucleotide polymorphism results in a missense mutation (385C3 A) that converts a conserved proline residue to threonine (Pro1293 Thr), producing a FAAH variant that displays normal catalytic properties but an enhanced sensitivity to proteolytic degradation. Collectively, these results suggest that genetic mutations in FAAH may constitute important risk factors for problem drug use and support a potential link between functional abnormalities in the endogenous cannabinoid system and drug abuse and dependence. D rug abuse and dependence are neurobehavioral disorders of complex origin in which both environmental and genetic factors are perceived to contribute to vulnerability (1). Genetic factors have been estimated to account for 40-60% of the risk in susceptible individuals (2). Although the primary molecular sites of action for many drugs of abuse are well characterized, efforts to identify genetic alterations in these neural signaling systems that are associated with problem drug use and addiction have, to date, been mostly unsuccessful (2). One neural signaling pathway generally implicated in drug abuse and addiction is the endogenous cannabinoid system (3). This system includes a G protein-coupled receptor CB1 that binds the principal psychoactive component of marijuana, ⌬-9-tetrahydrocannabinol, and the putative endogenous CB1 ligands, anandamide and 2-arachidonoylglycerol (4). Recent evidence suggests that the endogenous cannabinoid system may contribute not only to the development of dependence on marijuana (5) but also other drugs of abuse (6-8). Mice with a targeted disruption in the CB1 receptor exhibit reduced withdrawal responses to morphine (9), suggesting that significant crosstalk exists between endogenous opioid and cannabinoid systems in neural pathways that mediate addiction. Consistent with this notion, withdrawal from cannabinoids is significantly reduced in mice lacking preproenkephalin (10) or the -opioid receptor (11).Recently, a third central component of the endogenous cannabinoid system, the integral membrane enzyme fatty acid amide hydrolase (FAAH), has been identified (12-14). Several lines of evidence suggest that FAAH serves as a primary catabolic regulator of anandamide and related fatty acid amide-signaling molecules in vivo. Specifically, mice with a targeted disruption in the FAAH gene (FAAH Ϫ/Ϫ ) are severely impaired in their ability to degra...

Fatty acid amide hydrolase (FAAH) inactivates the endogenous cannabinoid (endocannabinoid) anandamide and related lipid transmitters in vivo. A single nucleotide polymorphism (SNP) in the human FAAH gene (385C to A) has recently been described that, in homozygous form, is over-represented in subjects with problem drug use. This SNP, which converts a conserved proline residue in FAAH to threonine (P129T), suggests a potential role for the FAAH-endocannabinoid system in regulating addictive behavior. Nonetheless, the impact of the 385A mutation on the biochemical and cellular function of FAAH remains unknown. Here, we report that T-lymphocytes isolated from patients homozygous for the P129T-FAAH variant express less than half of the FAAH protein and activity observed in wild-type (WT) lymphocytes. Transfected COS-7 cells also expressed significantly lower levels of P129T-FAAH compared with WT-FAAH, indicating that the aberrant expression of the former protein is not a cell type-specific phenomenon. A comparison of the transcription/translation efficiencies and cellular stabilities of WT- and P129T-FAAH proteins revealed that the reduced expression of the mutant enzyme is due to a post-translational mechanism that precedes productive folding. These findings indicate that the natural 385A SNP in the human FAAH gene produces a mutant enzyme with reduced cellular stability, thus fortifying a potential link between functional abnormalities in the endocannabinoid system and drug abuse and dependence.

Almost simultaneously, several studies reported the emergence of novel SARS-CoV-2 lineages characterized by their phylogenetic and genetic distinction (1), (2), (3), (4).…

In this study, we report the sequencing of 180 new viral genomes obtained from different municipalities of the state of Rio de Janeiro from April to December 2020. We identified a novel lineage of SARS-CoV-2, originated from B.1.1.28, distinguished by five single-nucleotide variants (SNVs): C100U, C28253U, G28628U, G28975U, and C29754U. The SNV G23012A (E484K), in the receptor-binding domain of Spike protein, was widely spread across the samples. This mutation was previously associated with escape from neutralizing antibodies against SARS-CoV-2. This novel lineage emerged in late July being first detected by us in late October and still mainly restricted to the capital of the state. However, as observed for other strains it can be rapidly spread in the state. The significant increase in the frequency of this lineage raises concerns about public health management and continuous need for genomic surveillance during the second wave of infections.Article Summary LineWe identified a novel circulating lineage of SARS-CoV-2 in the state of Rio de Janeiro Brazil originated from B.1.1.28 lineage.