Nanoparticle-based DNA vaccine protects against SARS-CoV-2 variants in female preclinical models.

A safe and effective vaccine with long-term protection against SARS-CoV-2 variants of concern (VOCs) is a global health priority. Here, we develop lipid nanoparticles (LNPs) to provide safe and effective delivery of plasmid DNA (pDNA) and show protection against VOCs in female small animal models. Using a library of LNPs encapsulating unique barcoded DNA (b-DNA), we screen for b-DNA delivery after intramuscular administration. The top-performing LNPs are further tested for their capacity of pDNA uptake in antigen-presenting cells in vitro. The lead LNP is used to encapsulate pDNA encoding the HexaPro version of SARS-CoV-2 spike (LNP-HPS) and immunogenicity and protection is tested in vivo. LNP-HPS elicit a robust protective effect against SARS-CoV-2 Gamma (P.1), correlating with reduced lethality, decreased viral load in the lungs and reduced lung damage. LNP-HPS induce potent humoral and T cell responses against P.1, and generate high levels of neutralizing antibodies against P.1 and Omicron (B.1.1.529). Our findings indicate that the protective efficacy and immunogenicity elicited by LNP-HPS are comparable to those achieved by the approved COVID-19 vaccine from Biontech/Pfizer in animal models. Together, these findings suggest that LNP-HPS hold great promise as a vaccine candidate against VOCs.

Clinical, immunological, and microbiological analysis of the association between periodontitis and COVID-19: a case-control study.

PURPOSE: Periodontitis and coronavirus disease (COVID-19) share risk factors and activate similar immunopathological pathways, intensifying systemic inflammation. This study investigated the clinical, immunological and microbiological parameters in individuals with COVID-19 and controls, exploring whether periodontitis-driven inflammation contributes to worsening COVID-19 endpoints. METHODS: Case (positive RT-PCR for SARS-CoV-2) and control (negative RT-PCR) individuals underwent clinical and periodontal assessments. Salivary levels of TNF-α, IL-6, IL-1ß, IL-10, OPG, RANKL, neutrophil extracellular traps, and subgingival biofilm were analyzed at two timepoints. Data on COVID-19-related outcomes and comorbidity information were evaluated from medical records. RESULTS: Ninety-nine cases of COVID-19 and 182 controls were included for analysis. Periodontitis was associated with more hospitalization (p = 0.009), more days in the intensive care unit (ICU) (p = 0.042), admission to the semi-ICU (p = 0.047), and greater need for oxygen therapy (p = 0.042). After adjustment for confounders, periodontitis resulted in a 1.13-fold increase in the chance of hospitalization. Salivary IL-6 levels (p = 0.010) were increased in individuals with COVID-19 and periodontitis. Periodontitis was associated with increased RANKL and IL-1ß after COVID-19. No significant changes were observed in the bacterial loads of the periodontopathogens Porphyromona gingivalis, Aggregatibacter actinomycetemcomitans, Tanerella forsythia, and Treponema denticola. CONCLUSIONS: Periodontitis was associated with worse COVID-19 outcomes, suggesting the relevance of periodontal care to reduce the burden of overall inflammation. Understanding the crosstalk between SARS-CoV-2 infection and chronic conditions such as periodontitis that can influence disease outcome is important to potentially prevent complications of COVID-19.

L protein characterization and in silico screening of putative broad range target molecules for pathogenic mammarenaviruses from South America.

The genus Mammarenavirus belonging to the family Arenaviridae encompasses pathogenic viral species capable of triggering severe diseases in humans, causing concern for the health system due to the high fatality rate associated with them. Currently, there is a dearth of specific therapies against pathogens of the genus. Natural products isolated from plants have impacted the development of drugs against several diseases. The Núcleo de Bioensaios, Biossíntese e Ecofisiologia de Produtos Naturais (NuBBE) database offers several natural compounds with antimicrobial activities that can be used in the development of new antiviral drugs. In this context, here we modeled the arenavirus L protein, multifunctional machinery essential for the viral replicative cycle, making this enzyme a potential candidate for targeting the development of antivirals against genus pathogens. Using the modeled L protein, a virtual screening was performed, which suggested eleven molecules from the NuBBE database that binds to the active site of the L protein, which was promising in the in silico predictions of absorption and toxicity analysis. The NuBBE 1642 molecule proved to be the best candidate for four of the five species evaluated, acting as a possible broad-spectrum molecule. Additionally, our results showed that the L protein is highly conserved among species of the genus, as well as presenting close phylogenetic relationships between many of the species studied, strengthening its candidacy as a therapeutic target. The data presented here demonstrate that some NuBBE molecules are potential ligands for the L protein of arenaviruses, which may help to contain possible outbreaks.Communicated by Ramaswamy H. Sarma.

Molecular detection and characterization of SARS-CoV-2 in cats and dogs of positive owners during the first COVID-19 wave in Brazil.

Despite previous reports of SARS-CoV-2 infection in dogs and cats worldwide, the type of swab sample used for its detection through RT-qPCR needs to be better compared and described. Accordingly, as part of a multicenter study in Brazil, the aim of the present study was to assess which rectal or oropharyngeal swabs would be more appropriate for detecting SARS-CoV-2 in cats and dogs, through viral load comparison. Pets of owners diagnosed with COVID-19 in the last 7 days were eligible. A total of 148 animals from four of the five Brazilian geographical regions were analyzed, among which 10/48 cats (20.83%) and 11/100 dogs (11.00%) were positive. The results suggested that oropharyngeal swabs should be considered for SARS-CoV-2 detection, particularly in cats, due to the higher cDNA viral load. Also, the genomic results showed similarities between SARS-CoV-2 animal variants and human variants that were circulating at the time of sampling, thus corroborating the existence of zooanthroponotic transmission. In conclusion, the present study highlighted the importance of SARS-CoV-2 monitoring among cats and dogs, as virus modification may indicate the possibility of mutations in animals and spillover back to owners. Thus, positive individuals should always self-isolate from their pets during COVID-19, to prevent trans-species transmission and mutation.

Molecular mimicry between Zika virus and central nervous system inflammatory demyelinating disorders: the role of NS5 Zika virus epitope and PLP autoantigens.

BACKGROUND: Evidence indicates a strong link between Zika virus (ZikV) and neurological complications. Acute myelitis, optic neuritis, polyneuropathy, and encephalomyelitis that mimic inflammatory idiopathic demyelination disorders (IIDD) after ZikV infection have been reported in Brazil. OBJECTIVE: The present study aims to investigate the possible occurrence of molecular mimicry between ZikV antigens and Multiple Sclerosis (MS) autoantigens, the most frequent IIDD of the central nervous system (CNS). METHODS: A retrospective cohort study with 305 patients admitted due to suspected arbovirus infection in Rio de Janeiro was performed, all subjects were submitted to neurological examination, and a biological sample was collected for serologic and molecular diagnostic. Bioinformatics tools were used to analyze the peptides shared between ZikV antigens and MS autoantigens. RESULTS: Of 305 patients, twenty-six were positive for ZikV and 4 presented IDD patterns found in MS cases. Sequence homology comparisons by bioinformatics approach between NS5 ZikV and PLP MS protein revealed a homology of 5/6 consecutive amino acids (CSSVPV/CSAVPV) with 83% identity, deducing a molecular mimicry. Analysis of the 3D structures revealed a similar conformation with alpha helix presentation. CONCLUSIONS: Molecular mimicry between NS5 Zika virus antigen and PLP MS autoantigens emerge as a possible mechanism for IDD spectrum in genetically susceptible individuals.

ANTECEDENTES: Evidências indicam uma forte ligação entre o vírus Zika (ZikV) e complicações neurológicas. Mielite aguda, neurite óptica, polineuropatia e encefalomielite que mimetizam distúrbios inflamatórios de desmielinização idiopáticos (DDII) após infecção por ZikV têm sido relatadas no Brasil. OBEJTIVO: O presente estudo tem como objetivo investigar a possível ocorrência de mimetismo molecular entre antígenos do ZikV e autoantígenos da Esclerose Múltipla (EM), a DDII mais frequente do sistema nervoso central (SNC). MéTODOS: Foi realizado um estudo de coorte retrospectivo com 305 pacientes internados por suspeita de infecção por arbovírus no Rio de Janeiro, todos os indivíduos foram submetidos a exame neurológico e coleta de amostra biológica para diagnóstico sorológico e molecular. Ferramentas de bioinformática foram usadas para analisar os peptídeos compartilhados entre antígenos do ZikV e autoantígenos da EM. RESULTADOS: Dos 305 pacientes, vinte e seis foram positivos para ZikV e 4 apresentaram padrão IDD encontrado em casos de EM. As comparações de homologia de sequência por abordagem de bioinformática entre a proteína NS5 ZikV e PLP EM revelaram uma homologia de 5/6 aminoácidos consecutivos (CSSVPV/CSAVPV) com 83% de identidade, deduzindo um mimetismo molecular. A análise das estruturas 3D revelou uma conformação semelhante com apresentação em alfa-hélice. CONCLUSõES: O mimetismo molecular entre o antígeno NS5 do vírus Zika e o autoantígeno PLP da EM surge como um possível mecanismo para o espectro IDD em indivíduos geneticamente suscetíveis.

SARS-CoV-2 Omicron BA.1, BA.2, and XAG identification during routine surveillance on a university campus in Belo Horizonte, Brazil, 2022.

We report SARS-CoV-2 genomic surveillance results between Belo Horizonte, Brazil's third and fourth case waves. Samples were obtained through a routine university monitoring COVID-19 program from the 9th to the 22nd epidemiological weeks (March and June 2022). We identified ten samples from the BA.1 clade (BA.1, BA.1.1, and BA.1.14.1 lineages) and 45 samples from the BA.2 clade (BA.2, BA.2.56, BA.2.9, BA.2.62, BA.2.23, BA.2.81, and BA.2.10). We observed progressive replacement of the BA.1 by the BA.2 clade. Furthermore, two XAG recombinants were found in the 22nd week. Diversification of the omicron variant seems to have contributed to the resurgence of cases in Belo Horizonte, similarly to what has been reported in South Africa.

Negative correlation between ACE2 gene expression levels and loss of taste in a cohort of COVID-19 hospitalized patients: New clues to long-term cognitive disorders.

In early 2020, one of the most prevalent symptoms of SARS-CoV-2 infection was the loss of smell (anosmia), found in 60-70% of all cases. Anosmia used to occur early, concomitantly with other symptoms, and often persisted after recovery for an extended period, sometimes for months. In addition to smell disturbance, COVID-19 has also been associated with loss of taste (ageusia). The latest research suggests that SARS-CoV-2 could spread from the respiratory system to the brain through receptors in sustentacular cells localized to the olfactory epithelium. The virus invades human cells via the obligatory receptor, angiotensin-converting enzyme II (ACE2), and a priming protease, TMPRSS2, facilitating viral penetration. There is an abundant expression of both ACE2 and TMPRSS2 in sustentacular cells. In this study, we evaluated 102 COVID-19 hospitalized patients, of which 17.60% presented anosmia and 9.80% ageusia. ACE1, ACE2, and TMPRSS2 gene expression levels in nasopharyngeal tissue were obtained by RT-qPCR and measured using ΔCT analysis. ACE1 Alu287bp association was also evaluated. Logistic regression models were generated to estimate the effects of variables on ageusia and anosmia Association of ACE2 expression levels with ageusia. was observed (OR: 1.35; 95% CI: 1.098-1.775); however, no association was observed between TMPRSS2 and ACE1 expression levels and ageusia. No association was observed among the three genes and anosmia, and the Alu287bp polymorphism was not associated with any of the outcomes. Lastly, we discuss whetherthere is a bridge linking these initial symptoms, including molecular factors, to long-term COVID-19 health consequences such as cognitive dysfunctions.

Biosafety in Dental Health Care During the COVID-19 Pandemic: A Longitudinal Study.

Background: The coronavirus disease 2019 (COVID-19) pandemic had quite an impact on dental health care. Concerns about the risk of SARS-CoV-2 transmission through contaminant fluids and droplet formation during several dental procedures highly impacted dental health care, drastically reducing the number of dental practices worldwide. To monitor SARS-CoV-2 contamination in dental clinics, a longitudinal study was carried out during the return of dental practice at university. Methods: Dental health care professionals [(DHCPs); teachers, undergraduate dental students, and dental assistants] and patients were screened for SARS-CoV-2 RNA in a dental school clinic environment from 11th January to 12th March 2021 (9 weeks). Serological testing was performed on DHCPs in two-time points. Additionally, samples with low Ct values were sequenced to identify the circulating SARS-CoV-2 variant and possible transmission clusters. Results: We found a low number of dental staff (5.8%), patients (0.9%), and environment sites (0.8%) positive for SARS-CoV-2. Most positive cases had asymptomatic to mild symptoms, and two asymptomatic DHCPs presented prolonged infection. In the first week after previous exposure to COVID-19, 16.2% of DHCPs had IgM or IgG antibodies against SARS-CoV-2, and 1/3 of them had undetected antibodies in the last weeks. The variant zeta (P.2) could be detected. No cross-infection was observed between participants. Conclusion: Our study suggests that dental practice can be safely executed when adequate control measures and biosafety protocols are applied. DHCP and patient testing, patient telemonitoring, proper use of personal protection equipment, and sanitization of surfaces are essential to avoid SARS-CoV-2 cross-infection in dental practice.

IFITM3, FURIN, ACE1, and TNF-α Genetic Association With COVID-19 Outcomes: Systematic Review and Meta-Analysis.

Human polymorphisms may contribute to SARS-CoV-2 infection susceptibility and COVID-19 outcomes (asymptomatic presentation, severe COVID-19, death). We aimed to evaluate the association of IFITM3, FURIN, ACE1, and TNF-α genetic variants with both phenotypes using meta-analysis. The bibliographic search was conducted on the PubMed and Scielo databases covering reports published until February 8, 2022. Two independent researchers examined the study quality using the Q-Genie tool. Using the Mantel-Haenszel weighted means method, odds ratios were combined under both fixed- and random-effect models. Twenty-seven studies were included in the systematic review (five with IFITM3, two with Furin, three with TNF-α, and 17 with ACE1) and 22 in the meta-analysis (IFITM3 n = 3, TNF-α, and ACE1 n = 16). Meta-analysis indicated no association of 1) ACE1 rs4646994 and susceptibility, 2) ACE1 rs4646994 and asymptomatic COVID-19, 3) IFITM3 rs12252 and ICU hospitalization, and 4) TNF-α rs1800629 and death. On the other hand, significant results were found for ACE1 rs4646994 association with COVID-19 severity (11 studies, 692 severe cases, and 1,433 nonsevere controls). The ACE1 rs4646994 deletion allele showed increased odds for severe manifestation (OR: 1.45; 95% CI: 1.26-1.66). The homozygous deletion was a risk factor (OR: 1.49, 95% CI: 1.22-1.83), while homozygous insertion presented a protective effect (OR: 0.57, 95% CI: 0.45-0.74). Further reports are needed to verify this effect on populations with different ethnic backgrounds. Systematic Review Registration: https://www.crd.york.ac.uk/prosperodisplay_record.php?ID=CRD42021268578, identifier CRD42021268578.

Seroprevalence, Prevalence, and Genomic Surveillance: Monitoring the Initial Phases of the SARS-CoV-2 Pandemic in Betim, Brazil.

The COVID-19 pandemic has created an unprecedented need for epidemiological monitoring using diverse strategies. We conducted a project combining prevalence, seroprevalence, and genomic surveillance approaches to describe the initial pandemic stages in Betim City, Brazil. We collected 3239 subjects in a population-based age-, sex- and neighborhood-stratified, household, prospective; cross-sectional study divided into three surveys 21 days apart sampling the same geographical area. In the first survey, overall prevalence (participants positive in serological or molecular tests) reached 0.46% (90% CI 0.12-0.80%), followed by 2.69% (90% CI 1.88-3.49%) in the second survey and 6.67% (90% CI 5.42-7.92%) in the third. The underreporting reached 11, 19.6, and 20.4 times in each survey. We observed increased odds to test positive in females compared to males (OR 1.88 95% CI 1.25-2.82), while the single best predictor for positivity was ageusia/anosmia (OR 8.12, 95% CI 4.72-13.98). Thirty-five SARS-CoV-2 genomes were sequenced, of which 18 were classified as lineage B.1.1.28, while 17 were B.1.1.33. Multiple independent viral introductions were observed. Integration of multiple epidemiological strategies was able to adequately describe COVID-19 dispersion in the city. Presented results have helped local government authorities to guide pandemic management.

Clinical and magnetic resonance imaging patterns of extensive Chikungunya virus-associated myelitis.

Chikungunya fever is an arbovirus infection transmitted by the same mosquito vector of dengue and Zika virus. Besides high fever, common clinical symptoms include articular pain and general malaise. Neurological involvement is unusual, but some patients may develop peripheral and central nervous system involvement, including meningoencephalitis, myelitis, Guillain-Barré syndrome, and acute disseminated encephalomyelitis. We present three cases of Chikungunya fever complicated with extensive myelitis. The spinal cord magnetic resonance imaging (MRI) pattern is characterized by multiple dotted-like and longitudinal hyperintense lesions, with contrast enhancement, mostly distributed in the peripheral regions of the spinal cord. It seems that these lesions are mostly located in the perivascular spaces (PVS), related or not to virus attack. Involvement of brain PVS can also be demonstrated, as shown in two of the cases described. Considering the MRI pattern, extensive spinal cord lesion should include Chikungunya as a differential diagnosis, especially during an outbreak.

Common Dysregulation of Innate Immunity Pathways in Human Primary Astrocytes Infected With Chikungunya, Mayaro, Oropouche, and Zika Viruses.

Arboviruses pose a major threat throughout the world and represent a great burden in tropical countries of South America. Although generally associated with moderate febrile illness, in more severe cases they can lead to neurological outcomes, such as encephalitis, Guillain-Barré syndrome, and Congenital Syndromes. In this context astrocytes play a central role in production of inflammatory cytokines, regulation of extracellular matrix, and control of glutamate driven neurotoxicity in the central nervous system. Here, we presented a comprehensive genome-wide transcriptome analysis of human primary astrocytes infected with Chikungunya, Mayaro, Oropouche, or Zika viruses. Analyses of differentially expressed genes (DEGs), pathway enrichment, and interactomes have shown that Alphaviruses up-regulated genes related to elastic fiber formation and N-glycosylation of glycoproteins, with down-regulation of cell cycle and DNA stability and chromosome maintenance genes. In contrast, Oropouche virus up-regulated cell cycle and DNA maintenance and condensation pathways while down-regulated extracellular matrix, collagen metabolism, glutamate and ion transporters pathways. Zika virus infection only up-regulated eukaryotic translation machinery while down-regulated interferon pathways. Reactome and integration analysis revealed a common signature in down-regulation of innate immune response, antiviral response, and inflammatory cytokines associated to interferon pathway for all arboviruses tested. Validation of interferon stimulated genes by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) corroborated our transcriptome findings. Altogether, our results showed a co-evolution in the mechanisms involved in the escape of arboviruses to antiviral immune response mediated by the interferon (IFN) pathway.

Genomic Evidence of SARS-CoV-2 Reinfection Involving E484K Spike Mutation, Brazil.

Uncertainty remains about how long the protective immune responses against severe acute respiratory syndrome coronavirus 2 persists, and suspected reinfection in recovered patients has been reported. We describe a case of reinfection from distinct virus lineages in Brazil harboring the E484K mutation, a variant associated with escape from neutralizing antibodies.

Chikungunya fever: How accurate is the clinical-epidemiological diagnosis compared to the gold standard of molecular and serological laboratory diagnosis?

OBJECTIVE: To evaluate the accuracy of the current World Health Organization' (WHO) Chikungunya fever (CHIKF) clinical-epidemiological case definition against the gold standard of laboratory diagnosis. METHODS: This was a prospective study of patients seeking medical care at an Emergency Department in the metropolitan area of Rio de Janeiro, Brazil, from January to June 2018. Clinical features were recorded. Screening for CHIKF was performed using the RT-qPCR and ELISA-IgM antibody assay. Clinical features of CHIKF RT-qPCR/IgM positive cases were compared with those with other febrile illnesses. RESULTS: 27,900 ED visits were recorded, of which 172 (0.61 %) patients were screened for arboviral illness. The prevalence of laboratory-confirmed CHIKF (Lab-CHIKF) was 110/172 [64 %]. Chikungunya virus RNA was detected in 92/172 (53.5 %) patients, while in 18/80 (10.5 %), only IgM was positive. Compared to CHIKV-negative subjects, patients with CHIKF presented much earlier after the onset of symptoms (2 [1-4] vs. 3.5 [2.5-5], p = 0.007), and more frequently reported arthritis (61.8 % vs. 33.9 %, p < 0.0001), arthralgia (96.4 % vs. 79 %, p < 0.0001), and conjunctivitis (35.5 % vs. 16.1 %, p = 0.007). After adjustments for other clinical predictors, arthritis/arthralgia [aOR: 6 (95 % CI 1.8-19.7)] and the presence of conjunctivitis [aOR: 2.85 (95 % CI 1.30-6.24] were positively associated with lab-CHIKF. The sensitivity, specificity, positive predictive value, and negative predictive value of the WHO CHIKF clinical case definition was 96.3 %, 20.9 %, 68.3 % and 76.4 %, respectively, and accuracy was 0.69 [AUC: 0.69 (95 % CI 0.61-0.75)]. CONCLUSION: The WHO case definition needs to be improved for better accuracy, especially in areas in epidemics in areas with co-circulation of arboviruses.

Association between MBL2 haplotypes and dengue severity in children from Rio de Janeiro, Brazil.

BACKGROUND: Dengue is an arthropod-borne viral disease with a majority of asymptomatic individuals and clinical manifestations varying from mild fever to severe and potentially lethal forms. An increasing number of genetic studies have outlined the association between host genetic variations and dengue severity. Genes associated to viral recognition and entry, as well as those encoding mediators of the immune response against infection are strong candidates for association studies. OBJECTIVES: The aim of this study was to investigate the association between MBL2, CLEC5A, ITGB3 and CCR5 genes and dengue severity in children. METHODS: A matched case-control study was conducted and 19 single nucleotide polymorphisms (SNPs) were investigated. FINDINGS: No associations were observed in single SNP analysis. However, when MBL2 SNPs were combined in haplotypes, the allele rs7095891G/rs1800450C/ rs1800451C/rs4935047A/rs930509G/rs2120131G/rs2099902C was significantly associated to risk of severe dengue under α = 0.05 (aOR = 4.02; p = 0.02). A second haplotype carrying rs4935047G and rs7095891G alleles was also associated to risk (aOR = 1.91; p = 0.04). MAIN CONCLUSIONS: This is the first study to demonstrate the association between MBL2 haplotypes and dengue severity in Brazilians including adjustment for genetic ancestry. These results reinforce the role of mannose binding lectin in immune response to DENV.

Association between MBL2 haplotypes and dengue severity in children from Rio de Janeiro, Brazil

BACKGROUND Dengue is an arthropod-borne viral disease with a majority of asymptomatic individuals and clinical manifestations varying from mild fever to severe and potentially lethal forms. An increasing number of genetic studies have outlined the association between host genetic variations and dengue severity. Genes associated to viral recognition and entry, as well as those encoding mediators of the immune response against infection are strong candidates for association studies. OBJECTIVES The aim of this study was to investigate the association between MBL2, CLEC5A, ITGB3 and CCR5 genes and dengue severity in children. METHODS A matched case-control study was conducted and 19 single nucleotide polymorphisms (SNPs) were investigated. FINDINGS No associations were observed in single SNP analysis. However, when MBL2 SNPs were combined in haplotypes, the allele rs7095891G/rs1800450C/ rs1800451C/rs4935047A/rs930509G/rs2120131G/rs2099902C was significantly associated to risk of severe dengue under α = 0.05 (aOR = 4.02; p = 0.02). A second haplotype carrying rs4935047G and rs7095891G alleles was also associated to risk (aOR = 1.91; p = 0.04). MAIN CONCLUSIONS This is the first study to demonstrate the association between MBL2 haplotypes and dengue severity in Brazilians including adjustment for genetic ancestry. These results reinforce the role of mannose binding lectin in immune response to DENV.

Chloroquine, an Endocytosis Blocking Agent, Inhibits Zika Virus Infection in Different Cell Models.

Zika virus (ZIKV) infection in utero might lead to microcephaly and other congenital defects. Since no specific therapy is available thus far, there is an urgent need for the discovery of agents capable of inhibiting its viral replication and deleterious effects. Chloroquine is widely used as an antimalarial drug, anti-inflammatory agent, and it also shows antiviral activity against several viruses. Here we show that chloroquine exhibits antiviral activity against ZIKV in Vero cells, human brain microvascular endothelial cells, human neural stem cells, and mouse neurospheres. We demonstrate that chloroquine reduces the number of ZIKV-infected cells in vitro, and inhibits virus production and cell death promoted by ZIKV infection without cytotoxic effects. In addition, chloroquine treatment partially reveres morphological changes induced by ZIKV infection in mouse neurospheres.

Natural Plant Alkaloid (Emetine) Inhibits HIV-1 Replication by Interfering with Reverse Transcriptase Activity.

Ipecac alkaloids are secondary metabolites produced in the medicinal plant Psychotria ipecacuanha. Emetine is the main alkaloid of ipecac and one of the active compounds in syrup of Ipecac with emetic property. Here we evaluated emetine's potential as an antiviral agent against Human Immunodeficiency Virus. We performed in vitro Reverse Transcriptase (RT) Assay and Natural Endogenous Reverse Transcriptase Activity Assay (NERT) to evaluate HIV RT inhibition. Emetine molecular docking on HIV-1 RT was also analyzed. Phenotypic assays were performed in non-lymphocytic and in Peripheral Blood Mononuclear Cells (PBMC) with HIV-1 wild-type and HIV-harboring RT-resistant mutation to Nucleoside Reverse Transcriptase Inhibitors (M184V). Our results showed that HIV-1 RT was blocked in the presence of emetine in both models: in vitro reactions with isolated HIV-1 RT and intravirion, measured by NERT. Emetine revealed a strong potential of inhibiting HIV-1 replication in both cellular models, reaching 80% of reduction in HIV-1 infection, with low cytotoxic effect. Emetine also blocked HIV-1 infection of RT M184V mutant. These results suggest that emetine is able to penetrate in intact HIV particles, and bind and block reverse transcription reaction, suggesting that it can be used as anti-HIV microbicide. Taken together, our findings provide additional pharmacological information on the potential therapeutic effects of emetine.