Key mutations on spike protein altering ACE2 receptor utilization and potentially expanding host range of emerging SARS‐CoV‐2 variants

alexandrossfakianakis shared this article with you from Inoreader Key mutations on spike protein altering ACE2 receptor utilization and potentially expanding host range of emerging SARS‐CoV‐2 variants via Journal of Medical Virology Abstract Increasing evidence supports inter-species transmission of SARS-CoV-2 variants from human to domestic or wild animals during the ongoing COVID-19 pandemic, which is posing great challenges to epidemic control. Clarifying the host range of emerging SARS-CoV-2 variants will provide instructive information for the containment of viral spillover. The spike protein (S) of SARS-CoV-2 is the key determinant of receptor utilization, and therefore amino acid mutations on S will probably alter viral host range. Here, in order to evaluate the impact of S mutations, we constructed 20 Hela cell lines stably expressing ACE2 orthologs from different animals, and prepared 27 pseudotyped SARS-CoV-2 carrying different spike mutants, among which 20 bear single mutation and the other 7 were cloned from emerging SARS-CoV-2 variants, including D614G, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), Lambda (B.1.429) and Mu (B.1.621). Using pseudoviral reporter assa y, we identified that the substitutions of T478I and N501Y enabled the pseudovirus to utilize chicken ACE2, indicating potential infectivity to avian species. Furthermore, the S mutants of real SARS-CoV-2 variants comprising N501Y showed significantly acquired abilities to infect cells expressing mouse ACE2, indicating a critical role of N501Y in expanding SARS-CoV-2 host range. In addition, A262S and T478I significantly enhanced the utilization of various mammals ACE2. In summary, our results indicated that T478I and N501Y substitutions were two S mutations important for receptor adaption of SARS-CoV-2, potentially contributing to the spillover of the virus to many other animal hosts. Therefore, more attention should be paid to SARS-CoV-2 variants with these two mutations. This article is protected by copyright. All rights reserved. View on Web

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Should Linezolid Replace Clindamycin as the Adjunctive Antimicrobial of Choice in Group A Streptococcal Necrotizing Soft Tissue Infection and Toxic Shock Syndrome? A Focused Debate

alexandrossfakianakis shared this article with you from Inoreader Should Linezolid Replace Clindamycin as the Adjunctive Antimicrobial of Choice in Group A Streptococcal Necrotizing Soft Tissue Infection and Toxic Shock Syndrome? A Focused Debate via Clinical Infectious Diseases Advance Access Abstract Group A Streptococcus (GAS) necrotizing soft tissue infections and toxic shock syndrome remain high-mortality conditions. In vitro and animal model data, as well as multiple observational studies, suggest adjunctive clindamycin (i.e., given with a beta-lactam) reduces invasive GAS infection mortality by inhibiting exotoxin production. Unfortunately, clindamycin resistance in GAS has been rapidly increasing in the United States (US) since the mid-2010s, though the clinical significance of this remains unclear. Linezolid is a promising alternative adjunctive agent to which US GAS isolates remain near-universally susceptible, with a similar mechanism of action and similar in vitro evidence of GAS virulence factor attenuation. However, the clinical data supporting linezolid's value in severe GAS infections are far more limited. Here, the authors review the data and reasoning behind a general preference for clindamycin or linezolid in a focused, pro-con debate format. View on Web

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Estimating Waning of Vaccine Effectiveness: a Simulation Study

alexandrossfakianakis shared this article with you from Inoreader Estimating Waning of Vaccine Effectiveness: a Simulation Study via Clinical Infectious Diseases Advance Access Abstract Background Developing accurate and reliable methods to estimate vaccine protection is a key goal in immunology and public health. While several statistical methods have been proposed, their potential inaccuracy in capturing fast intra-seasonal waning of vaccine-induced protection needs to be rigorously investigated. Methods To compare statistical methods for vaccine effectiveness (VE) estimation, we generated simulated data using a multiscale agent-base d model of an epidemic with an acute viral infection and differing extents of VE waning. We apply a previously proposed framework for VE measures based on the observational data richness to assess changes of vaccine-induced protection over time. Results While VE measures based on hard-to-collect information (e.g. the exact timing of exposures) were accurate, usually VE studies rely on time-to-infection data and the Cox proportional hazard model. We found that its extension utilizing scaled Schoenfeld residuals, previously proposed for capturing VE waning, was unreliable in capturing both the degree of waning and its functional form and identified the mathematical factors contributing to this unreliability. We showed that partitioning time and including a time-vaccine interaction term in the Cox model significantly improved estimation of VE waning, even in the case of dramatic, rapid waning. We also proposed how to optimize the partitioning scheme. Conclusions While appropriate for rejecting the null hypothesis of no waning, scaled Schoenfeld residuals are unreliable for estimating the degree of waning. We propose a Cox-model-based method with a time-vaccine interaction term and further optimization of partitioning time. These findings may guide future analysis of VE waning data. View on Web

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WHOLE GENOME SEQUENCING OF SARS‐CoV‐2: COMPARISON OF TARGET CAPTURE AND AMPLICON SINGLE MOLECULAR REAL TIME SEQUENCING PROTOCOLS

alexandrossfakianakis shared this article with you from Inoreader WHOLE GENOME SEQUENCING OF SARS‐CoV‐2: COMPARISON OF TARGET CAPTURE AND AMPLICON SINGLE MOLECULAR REAL TIME SEQUENCING PROTOCOLS via Journal of Medical Virology ABSTRACT Fast, accurate sequencing methods are needed to identify new variants and genetic mutations of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome. Single Molecular Real Time (SMRT) Pacific Biosciences (PacBio) provides long, highly accurate sequences by circular consensus reads. This study compares the performance of a target capture SMRT Pacbio protocol for whole genome sequencing (WGS) of SARS-CoV-2 to that of an amplicon Pacbio SMRT sequencing protocol. The median genome coverage was higher (p<0.05) with the target capture protocol (99.3% [IQR: 96.3-99.5]) than with the amplicon protocol (99.3% [IQR :69.9-99.3]). The clades of 65 samples determined with both protocols were 100% concordant. After adjusting for Ct values, S gene coverage was higher with the target capture protocol than with the amplicon protocol. After stratification on Ct values, higher S gene coverage with the target capture protocol was observed only for samples w ith Ct>17 (p<0.01). Pacbio SMRT sequencing protocols appears to be suitable for WGS, genotyping and detecting mutations of SARS-CoV-2. This article is protected by copyright. All rights reserved. View on Web

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Translucency, color stability, and biaxial flexural strength of advanced lithium disilicate ceramic after coffee thermocycling

alexandrossfakianakis shared this article with you from Inoreader Translucency, color stability, and biaxial flexural strength of advanced lithium disilicate ceramic after coffee thermocycling via Journal of Esthetic and Restorative Dentistry Abstract Objective To compare the color stability, translucency, and biaxial flexural strength (BFS) of differently glazed advanced lithium disilicate (ALDS) with those of lithium disilicate (LDS) and zirconia-reinforced lithium silicate (ZLS) after coffee thermocycling. Materials and methods Forty disk-shaped specimens were prepared from three lithium silicate based materials (CEREC Tessera, ALDS; IPS e.max CAD, LDS; Vita Suprinity, ZLS). ALDS specimens were divided into two subgroups according to glazing procedures (reduced glaze duration, ALDS-S and normal glaze duration, ALDS-N), while LDS and ZLS specimens were crystallized and glazed. Color coordinate measurements were performed before and after coffee thermocycling. Color differences (ΔE 00) and relative translucency parameters (RTP) were calculated. Specimens were then subjected to BFS test. Statistical analysis was performed by using 1- (ΔE 00 and BFS) and 2-way (RTP) ANOVA tests (α = 0.05). Results ΔE 00 values of tested materials were similar (df = 3, F = 0.150, p = 0.929). Two-way ANOVA showed the significant effect of material type, coffee thermocycling, and the interaction between these parameters on RTP values (p < 0.001). Both before and after thermocycling, LDS had the highest (p ≤ 0.001) and ZLS had the lowest (p < 0.001) RTP values, while ALDS-N had higher RTP than ALDS-S (p ≤ 0.001). Among tested materials, only LDS had similar RTP values before and after thermocycling (p = 0.865) as the other materials had lower RTP values after thermocycling (p < 0.001). ALDS-N had higher BFS values than ALDS-S (p = 0.005), while LDS had similar values to ALDS specimens (p ≥ 0.201). ZLS had the highest BFS (p ≤ 0.007). Conclusions ALDS had comparable values to those of other materials. However, reduced glazing duration resulted in decreased translucency and BFS of ALDS. Clinical significance ALDS may be an appropriate restorative material for those patients with increased coffee consumption considering its color stability and ability to maintain translucency, particularly when glazed by using a conventional porcelain furnace. View on Web

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