18 research outputs found

    SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses

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    On 24th November 2021, the sequence of a new SARS-CoV-2 viral isolate Omicron-B.1.1.529 was announced, containing far more mutations in Spike (S) than previously reported variants. Neutralization titers of Omicron by sera from vaccinees and convalescent subjects infected with early pandemic Alpha, Beta, Gamma, or Delta are substantially reduced, or the sera failed to neutralize. Titers against Omicron are boosted by third vaccine doses and are high in both vaccinated individuals and those infected by Delta. Mutations in Omicron knock out or substantially reduce neutralization by most of the large panel of potent monoclonal antibodies and antibodies under commercial development. Omicron S has structural changes from earlier viruses and uses mutations that confer tight binding to ACE2 to unleash evolution driven by immune escape. This leads to a large number of mutations in the ACE2 binding site and rebalances receptor affinity to that of earlier pandemic viruses

    Identification of Primary Drug Resistance to Rifampin in Mycobacterium leprae Strains from Leprosy Patients in Amazonas State, Brazil

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    The aim of this study was to identify polymorphisms in the folp1, gyrA, and rpoB genes in leprosy patients treated in Amazonas State, Brazil. Among 197 slit-skin smear samples from untreated or relapsed patients, we found three cases of primary resistance to rifampin and one confirmed case of multidrug resistance

    In silico analysis of non-structural protein 12 sequences from SARS-COV-2 found in Manaus, Amazonas, Brazil, reveals mutations linked to higher transmissibility

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    Abstract The disease coronavirus COVID-19 has been the cause of millions of deaths worldwide. Among the proteins of SARS-CoV-2, non-structural protein 12 (NSP12) plays a key role during COVID infection and is part of the RNA-dependent RNA polymerase complex. The monitoring of NSP12 polymorphisms is extremely important for the design of new antiviral drugs and monitoring of viral evolution. This study analyzed the NSP12 mutations detected in circulating SARS-CoV-2 during the years 2020 to 2022 in the population of the city of Manaus, Amazonas, Brazil. The most frequent mutations found were P323L and G671S. Reports in the literature indicate that these mutations are related to transmissibility efficiency, which may have contributed to the extremely high numbers of cases in this location. In addition, two mutations described here (E796D and R914K) are close and have RMSD that is similar to the mutations M794V and N911K, which have been described in the literature as influential on the performance of the NSP12 enzyme. These data demonstrate the need to monitor the emergence of new mutations in NSP12 in order to better understand their consequences for the treatments currently used and in the design of new drugs

    Genomic and epidemiological surveillance of Zika virus in the Amazon region

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    Zika virus (ZIKV) has caused an explosive epidemic linked to severe clinical outcomes in the Americas. Until June 2018, 4,929 ZIKV suspected infections and 46 congenital syndrome cases were reported in Manaus city, Amazonas State, Brazil. Although Manaus is a key demographic hub in the Amazon region, little is known about the ZIKV epidemic there, both in terms of transmission and viral genetic diversity. Using portable virus genome sequencing we generated 59 ZIKV genomes in Manaus. Phylogenetic analyses indicated multiple introductions of ZIKV from northeast Brazil to Manaus. Spatial genomic analysis of virus movement among 6 areas in Manaus suggested that populous northern neighborhoods acted as sources of virus transmission to other neighborhoods. Our study revealed how the ZIKV epidemic was ignited and maintained within the largest urban metropolis in the Amazon. Those results might contribute to improve public health response to outbreaks in Brazil
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