Simulations support the interaction of the SARS-CoV-2 spike protein with nicotinic acetylcholine receptors and suggest subtype specificity

Changeux et al. recently suggested that the SARS-CoV-2 spike (S) protein may interact with nicotinic acetylcholine receptors (nAChRs). Such interactions may be involved in pathology and infectivity. Here, we use molecular simulations of validated atomically detailed structures of nAChRs, and of the S protein, to investigate this nicotinic hypothesis. We examine the binding of the Y674-R685 loop of the S protein to three nAChRs, namely the human 4{beta}2 and 7 subtypes and the muscle-like {beta}{gamma}d receptor from Tetronarce californica. Our results indicate that Y674-R685 has affinity for nAChRs and the region responsible for binding contains the PRRA motif, a four-residue insertion not found in other SARS-like coronaviruses. In particular, R682 has a key role in the stabilisation of the complexes as it forms interactions with loops A, B and C in the receptors binding pocket. The conformational behaviour of the bound Y674-R685 region is highly dependent on the receptor subtype, adopting extended conformations in the 4{beta}2 and 7 complexes and more compact ones when bound to the muscle-like receptor. In the 4{beta}2 and {beta}{gamma}d complexes, the interaction of Y674-R685 with the receptors forces the loop C region to adopt an open conformation similar to other known nAChR antagonists. In contrast, in the 7 complex, Y674-R685 penetrates deeply into the binding pocket where it forms interactions with the residues lining the aromatic box, namely with TrpB, TyrC1 and TyrC2. Estimates of binding energy suggest that Y674-R685 forms stable complexes with all three nAChR subtypes. Analyses of the simulations of the full-length S protein show that the Y674-R685 region is accessible for binding, and suggest a potential binding orientation of the S protein with nAChRs.

Prevalence and incidence estimates for syphilis, chlamydia, gonorrhea, and congenital syphilis in Colombia, 1995-2016.

OBJECTIVES: To estimate adult (15-49 years old) prevalence and incidence of active syphilis, gonorrhea, and chlamydia, and incidence of congenital syphilis (CS) and adverse birth outcomes (ABOs) in Colombia, over 1995-2016. METHODS: The Spectrum-STI epidemiological model tool estimated gonorrhea and chlamydia prevalences as moving averages across prevalences observed in representative general population surveys. For adult syphilis, Spectrum-STI applied segmented polynomial regression through prevalence data from antenatal care (ANC) surveys, routine ANC-based screening, and general population surveys. CS cases and ABOs were estimated from Spectrum's maternal syphilis estimates and proportions of women screened and treated for syphilis, applying World Health Organization case definitions and risk probabilities. RESULTS: The Spectrum model estimated prevalences in 2016 of 0.70% (95% confidence interval (CI): 0.15%-1.9%) in women and 0.60% (0.1%-1.9%) in men for gonorrhea and of 9.2% (4.4%-15.4%) in women and 7.4% (3.5%-14.7%) in men for chlamydia, without evidence for trends over 1995-2016. The prevalence of active syphilis in 2016 was 1.25% (1.22-1.29%) in women and 1.25% (1.1%-1.4%) in men, decreasing from 2.6% (2.1%-3.2%) in women in 1995. Corresponding CS cases in 2016 (including cases without clinical symptoms) totaled 3 851, of which 2 245 were ABOs. Annual CS and ABO estimates decreased over 2008-2016, reflecting decreasing maternal prevalence and increasing cases averted through ANC-based screening and treatment. CONCLUSIONS: The available surveillance and monitoring data synthesized in Spectrum-STI- and the resulting first-ever national STI estimates for Colombia-highlighted Colombia's persistently high STI burden. Adult syphilis and congenital syphilis are estimated to be falling, reflecting improving screening efforts. Strengthened surveillance, including with periodic screening in low-risk populations and future refined Spectrum estimations, should support planning and implementation of STI prevention and control, including CS elimination.

Prevalence and incidence estimates for syphilis, chlamydia, gonorrhea, and congenital syphilis in Colombia, 1995-2016 / Estimaciones sobre la prevalencia y la incidencia de sífilis, clamidiasis, gonorrea y sífilis congénita en Colombia, 1995-2016 / Estimativas da incidência e prevalência de sífilis, clamídia, gonorreia e sífilis congênita na Colômbia, 1995-2016

ABSTRACT Objectives To estimate adult (15-49 years old) prevalence and incidence of active syphilis, gonorrhea, and chlamydia, and incidence of congenital syphilis (CS) and adverse birth outcomes (ABOs) in Colombia, over 1995-2016. Methods The Spectrum-STI epidemiological model tool estimated gonorrhea and chlamydia prevalences as moving averages across prevalences observed in representative general population surveys. For adult syphilis, Spectrum-STI applied segmented polynomial regression through prevalence data from antenatal care (ANC) surveys, routine ANC-based screening, and general population surveys. CS cases and ABOs were estimated from Spectrum's maternal syphilis estimates and proportions of women screened and treated for syphilis, applying World Health Organization case definitions and risk probabilities. Results The Spectrum model estimated prevalences in 2016 of 0.70% (95% confidence interval (CI): 0.15%-1.9%) in women and 0.60% (0.1%-1.9%) in men for gonorrhea and of 9.2% (4.4%-15.4%) in women and 7.4% (3.5%-14.7%) in men for chlamydia, without evidence for trends over 1995-2016. The prevalence of active syphilis in 2016 was 1.25% (1.22-1.29%) in women and 1.25% (1.1%-1.4%) in men, decreasing from 2.6% (2.1%-3.2%) in women in 1995. Corresponding CS cases in 2016 (including cases without clinical symptoms) totaled 3 851, of which 2 245 were ABOs. Annual CS and ABO estimates decreased over 2008-2016, reflecting decreasing maternal prevalence and increasing cases averted through ANC-based screening and treatment. Conclusions The available surveillance and monitoring data synthesized in Spectrum-STI— and the resulting first-ever national STI estimates for Colombia—highlighted Colombia's persistently high STI burden. Adult syphilis and congenital syphilis are estimated to be falling, reflecting improving screening efforts. Strengthened surveillance, including with periodic screening in low-risk populations and future refined Spectrum estimations, should support planning and implementation of STI prevention and control, including CS elimination.

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RESUMO Objetivos Estimar a incidência e a prevalência na população adulta (com idade de 15-49 anos) de sífilis ativa, gonorreia e clamídia e a incidência de sífilis congênita (SC) e desfechos adversos congênitos na Colômbia no período de 1995 a 2016. Métodos O modelo epidemiológico Spectrum-STI foi o instrumento usado para estimar a prevalência de gonorreia e clamídia como médias móveis nas prevalências observadas em pesquisas representativas da população geral. A sífilis em adultos foi estimada com a regressão polinomial segmentada aplicada ao modelo Spectrum-STI com dados de prevalência obtidos de pesquisas da atenção pré-natal, exames pré-natais de rotina de detecção precoce e pesquisas da população geral. Casos de SC e desfechos adversos congênitos foram estimados a partir das estimativas de sífilis materna do modelo Spectrum e percentuais de mulheres que fizeram testes de detecção e foram tratadas para sífilis, segundo as definições de casos da Organização Mundial da Saúde (OMS) e probabilidades de risco. Resultados O modelo Spectrum estimou, para 2016, uma prevalência de gonorreia de 0,70% (intervalo de confiança de 95% [IC 95%] 0,15%-1,9%) no sexo feminino e 0,60% (0,1%-1,9%) no sexo masculino e uma prevalência de clamídia de 9,2% (4,4%-15,4%) no sexo feminino e 7,4% (3,5%-14.7%) no sexo masculino, sem evidência de tendências no período 1995-2016. A prevalência de sífilis ativa em 2016 foi de 1,25% (1,22-1,29%) no sexo feminino e 1,25% (1,1%-1,4%) no sexo masculino, demonstrando um declínio da prevalência de 2,6% (2,1%-3,2%) observada em 1995 para o sexo feminino. Houve, ao todo, 3.851 casos correspondentes de SC em 2016 (incluindo casos assintomáticos), dos quais 2.245 foram desfechos adversos congênitos. Observou-se uma redução nas estimativas anuais de SC e desfechos adversos congênitos em 2008-2016, refletindo a diminuição da prevalência materna e o número crescente de casos evitados com exames pré-natais de detecção e tratamento. Conclusões Os dados disponíveis de vigilância e monitoramento condensados no modelo Spectrum-STI, e as resultantes estimativas nacionais de infeções sexualmente transmissíveis (IST) obtidas pela primeira vez na Colômbia, evidenciam a alta carga persistente de IST no país. Estima-se que a ocorrência de sífilis do adulto e sífilis congênita esteja diminuindo em decorrência da melhoria nos esforços de detecção precoce. A vigilância reforçada, consistindo também de exames periódicos de detecção precoce nas populações de baixo risco e estimavas futuras aprimoradas do instrumento Spectrum, deve sustentar o planejamento e a implementação de controle e prevenção de IST e a eliminação da SC.

Parvimonas micra chest wall abscess following transthoracic lung needle biopsy

No abstract available.