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1.
Biologicals ; 2022 Sep 02.
Article in English | MEDLINE | ID: covidwho-2007466

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in Wuhan, China, is the causative agent of the coronavirus disease 2019 (COVID-19). Since its first notification in São Paulo state (SP) on 26th February 2020, more than 22,300,000 cases and 619,000 deaths were reported in Brazil. In early pandemic, SARS-CoV-2 spread locally, however, over time, this virus was disseminated to other regions of the country. Herein, we performed genomic sequencing and phylogenetic analysis of SARS-CoV-2 using 20 clinical samples of COVID-19 confirmed cases from 9 cities of Minas Gerais state (MG), in order to evaluate the molecular properties of circulating viral strains in this locality from March to May 2020. Our analyses demonstrated the circulation of B.1 lineage isolates in the investigated locations and nucleotide substitutions were observed into the genomic regions related to important viral structures. Additionally, sequences generated in this study clustered with isolates from SP, suggesting a dissemination route between these two states. Alternatively, monophyletic groups of sequences from MG and other states or country were observed, indicating independent events of virus introduction. These results reinforce the need of genomic surveillance for understand the ongoing spread of emerging viral pathogens.

2.
Virulence ; 13(1): 1031-1048, 2022 12.
Article in English | MEDLINE | ID: covidwho-1900978

ABSTRACT

The ongoing COVID-19 pandemic caused a significant loss of human lives and a worldwide decline in quality of life. Treatment of COVID-19 patients is challenging, and specific treatments to reduce COVID-19 aggravation and mortality are still necessary. Here, we describe the discovery of a novel class of epiandrosterone steroidal compounds with cationic amphiphilic properties that present antiviral activity against SARS-CoV-2 in the low micromolar range. Compounds were identified in screening campaigns using a cytopathic effect-based assay in Vero CCL81 cells, followed by hit compound validation and characterization. Compounds LNB167 and LNB169 were selected due to their ability to reduce the levels of infectious viral progeny and viral RNA levels in Vero CCL81, HEK293, and HuH7.5 cell lines. Mechanistic studies in Vero CCL81 cells indicated that LNB167 and LNB169 inhibited the initial phase of viral replication through mechanisms involving modulation of membrane lipids and cholesterol in host cells. Selection of viral variants resistant to steroidal compound treatment revealed single mutations on transmembrane, lipid membrane-interacting Spike and Envelope proteins. Finally, in vivo testing using the hACE2 transgenic mouse model indicated that SARS-CoV-2 infection could not be ameliorated by LNB167 treatment. We conclude that anti-SARS-CoV-2 activities of steroidal compounds LNB167 and LNB169 are likely host-targeted, consistent with the properties of cationic amphiphilic compounds that modulate host cell lipid biology. Although effective in vitro, protective effects were cell-type specific and did not translate to protection in vivo, indicating that subversion of lipid membrane physiology is an important, yet complex mechanism involved in SARS-CoV-2 replication and pathogenesis.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Antiviral Agents/pharmacology , COVID-19/drug therapy , Chlorocebus aethiops , HEK293 Cells , Humans , Lipids , Mice , Pandemics , Quality of Life , Vero Cells , Virus Replication
3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-315929

ABSTRACT

Background: The Gamma variant has been considered the predominant SARS-CoV-2 lineage in Brazil during the first half of 2021. We aimed to characterise the clinical presentation of COVID-19 caused by the Gamma variant in comparison with strains that are not variants of concern (non-VoC).Method: We performed a prospective cohort study including symptomatic COVID-19 cases among healthcare workers from January 22 to May 15, 2021. Positive samples for SARS-CoV-2 RT-PCR underwent whole genome sequencing. COVID-19 symptoms, caused by the Gamma variant or non-VoC, and risk factors for Gamma variant infection were evaluated using multiple logistic regression analyses.Findings: We included 423 COVID-19 cases, of which 415 (98%) with mild disease. One hundred and seventy-five (41%) patients had been fully immunised, of which 173/175 (99%) had received CoronaVac. There were 313 (74%) Gamma variant cases and 110 (26%) non-VoC cases. Hyposmia/anosmia and dysgeusia were present in 129 (30%) and 108 (26%) of cases, respectively. Lower frequencies of hyposmia/anosmia (OR=0.304, p <0.001) and dysgeusia (OR=0.385, p =0.011) were the only symptoms significantly associated with Gamma variant infection. COVID-19 immunisation, previous COVID-19 and age were not associated with Gamma variant infection.Interpretation: The increase in Gamma variant cases should raise the awareness that COVID-19 may present more often with cold-like symptoms because of a decreased frequency of hyposmia/anosmia and dysgeusia.Funding: Supported by the Itau Unibanco “Todos pela saúde” program”.Declaration of Interest: None to declare. Ethical Approval: This study was approved by the Hospital’s Ethics Committee (CAAE: 42708721.0.0000.0068).

4.
Emerg Infect Dis ; 27(3): 970-972, 2021 03.
Article in English | MEDLINE | ID: covidwho-1048946

ABSTRACT

In December 2020, research surveillance detected the B.1.1.7 lineage of severe acute respiratory syndrome coronavirus 2 in São Paulo, Brazil. Rapid genomic sequencing and phylogenetic analysis revealed 2 distinct introductions of the lineage. One patient reported no international travel. There may be more infections with this lineage in Brazil than reported.


Subject(s)
COVID-19 , Phylogeny , SARS-CoV-2/isolation & purification , Travel , Adult , Brazil , COVID-19/epidemiology , COVID-19/virology , Female , Genome, Viral , Humans , Male , Young Adult
5.
Rev Inst Med Trop Sao Paulo ; 62: e30, 2020.
Article in English | MEDLINE | ID: covidwho-246727

ABSTRACT

We conducted the genome sequencing and analysis of the first confirmed COVID-19 infections in Brazil. Rapid sequencing coupled with phylogenetic analyses in the context of travel history corroborate multiple independent importations from Italy and local spread during the initial stage of COVID-19 transmission in Brazil.


Subject(s)
Betacoronavirus/genetics , Communicable Diseases, Imported/transmission , Coronavirus Infections/transmission , Pandemics , Pneumonia, Viral/transmission , Aged , Brazil/epidemiology , COVID-19 , Communicable Diseases, Imported/epidemiology , Communicable Diseases, Imported/virology , Coronavirus Infections/epidemiology , Humans , Middle Aged , Phylogeny , Pneumonia, Viral/epidemiology , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2
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