The effect of the rapid accumulation of nonsynonymous mutations on the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not yet known. The 3a protein is unique to SARS-CoV and is essential for disease pathogenesis. Our study aimed at determining the nonsynonymous mutations in the 3a protein in SARS-CoV-2 and determining and characterizing the protein's structure and spatial orientation in comparison to those of 3a in SARS-CoV. A total of 51 different nonsynonymous amino acid substitutions were detected in the 3a proteins among 2,782 SARS-CoV-2 strains. We observed microclonality within the ORF3a gene tree defined by nonsynonymous mutations separating the isolates into distinct subpopulations. We detected and identified six functional domains (I to VI) in the SARS-CoV-2 3a protein. The functional domains were linked to virulence, infectivity, ion channel formation, and virus release. Our study showed the importance of conserved functional domains across the species barrier and revealed the possible role of the 3a protein in the viral life cycle. Observations reported in this study merit experimental confirmation.IMPORTANCE At the surge of the coronavirus disease 2019 (COVID-19) pandemic, we detected and identified six functional domains (I to VI) in the SARS-CoV-2 3a protein. Our analysis showed that the functional domains were linked to virulence, infectivity, ion channel formation, and virus release in SARS-CoV-2 3a. Our study also revealed the functional importance of conserved domains across the species barrier. Observations reported in this study merit experimental confirmation.

Streptococcus intermedius is a β-hemolytic Gram-positive member of the Streptococcus anginosus group (SAG). Despite being a part of the normal microbiota, it is one of the most common pathogens associated with brain and liver abscesses and thoracic empyema, increasing as a result the morbidity and mortality rates in affected patients. Though there are numerous published case reports on S. intermedius infections, it is still understudied compared to other SAG members. Our knowledge of the genomic factors contributing to its dissemination to the brain and abscess development is also limited to few characterized genes. In this review, we summarize our current knowledge on S. intermedius identification methods, virulence factors, and insight provided by the whole-genome and correlate patients' metadata, symptoms, and disease outcome with S. intermedius infections in 101 recent case reports obtained from PubMed. This combined information highlights the gaps in our understanding of S. intermedius pathogenesis, suggesting future research directions to unveil the factors contributing to abscess development.

The COVID-19 pandemic created a worldwide debilitating health crisis with the entire humanity suffering from the deleterious effects associated with the high infectivity and mortality rates. While significant evidence is currently available online and targets various aspects of the disease, both inflammatory and noninflammatory kidney manifestations secondary to COVID-19 infection are still largely underrepresented. In this review, we summarized current knowledge about COVID-19-related kidney manifestations, their pathologic mechanisms as well as various pharmacotherapies used to treat patients with COVID-19. We also shed light on the effect of these medications on kidney functions that can further enhance renal damage secondary to the illness.

AbstractThe effect of the rapid accumulation of non-synonymous mutations on the pathogenesis of SARS-CoV-2 is not yet known. To predict the impact of non-synonymous mutations and polyproline regions identified in ORF3a on the formation of B-cell epitopes and their role in evading the immune response, nucleotide and protein sequences of 537 available SARS-CoV-2 genomes were analyzed for the presence of non-synonymous mutations and polyproline regions. Mutations were correlated with changes in epitope formation. A total of 19 different non-synonymous amino acids substitutions were detected in ORF3a among 537 SARS-CoV-2 strains. G251V was the most common and identified in 9.9% (n=53) of the strains and was predicted to lead to the loss of a B-cell like epitope in ORF3a. Polyproline regions were detected in two strains (EPI_ISL_410486, France and EPI_ISL_407079, Finland) and affected epitopes formation. The accumulation of non-synonymous mutations and detected polyproline regions in ORF3a of SARS-CoV-2 could be driving the evasion of the host immune response thus favoring viral spread. Rapid mutations accumulating in ORF3a should be closely monitored throughout the COVID-19 pandemic.ImportanceAt the surge of the COVID-19 pandemic and after three months of the identification of SARS-CoV-2 as the disease-causing pathogen, nucleic acid changes due to host-pathogen interactions are insightful into the evolution of this virus. In this paper, we have identified a set of non-synonymous mutations in ORF3a and predicted their impact on B-cell like epitope formation. The accumulation of non-synonymous mutations in ORF3a could be driving protein changes that mediate immune evasion and favoring viral spread.

Streptococcus intermedius (SI) is associated with prolonged hospitalization and low survival rates. The genetic mechanisms involved in brain abscess development and genome evolution in comparison to other members of the Streptococcus anginosus group are understudied. We performed a whole-genome comparative analysis of an SI isolate, LAU_SINT, associated with brain abscess following sinusitis with all SI genomes in addition to S. constellatus and S. anginosus. Selective pressure on virulence factors, phages, pan-genome evolution and single-nucleotide polymorphism analysis were assessed. The structural details of the type seven secretion system (T7SS) was elucidated and compared with different organisms. ily and nanA were both abundant and conserved. Nisin resistance determinants were found in 47% of the isolates. Pan-genome and SNPs-based analysis didn’t reveal significant geo-patterns. Our results showed that two SC isolates were misidentified as SI. We propose the presence of four T7SS modules (I–IV) located on various genomic islands. We detected a variety of factors linked to metal ions binding on the GIs carrying T7SS. This is the first detailed report characterizing the T7SS and its link to nisin resistance and metal ions binding in SI. These and yet uncharacterized T7SS transmembrane proteins merit further studies and could represent potential therapeutic targets.