RESUMO
SARS-CoV-2, the causative virus for COVID-19 has now super-mutated into the Omicron (Om) variant. On its spike (S) glycoprotein alone, more than 30 substitutions have been characterized with 15 within the receptor binding domain (RBD); It therefore calls to question the transmissibility and antibody escapability of Omicron. This study was setup to investigate the Omicron RBD's interaction with ACE2 (host receptor) and a SARS-CoV-2 neutralizing monoclonal antibody (mAb). In-silico mutagenesis was used to generate the Om-RBD in complex with ACE2 or mAb from the wildtype. HDOCK server was used to redock and score the mAbs in Om-RBD bound state relative to the wildtype. Stability of interaction between all complexes were investigated using all-atom molecular dynamics (MD). Analyses of trajectories showed that Om-RBD has evolved into an efficient ACE2 binder, via pi-pi (Om-RBD-Y501/ACE2-Y41) and salt-bridge (Om-RBD-K493/ACE2-Y41) interactions. Conversely, in binding mAb, it has become less efficient (Center of mass distance of RBD from mAb complex, wildtype ≈ 30 Å, Omicron ≈ 41 Å). Disruption of Om-RBD/mAb complex resulted from loose interaction between Om-RBD and the light chain complementarity-determining region residues. Omicron is expected to be better transmissible and less efficiently interacting with neutralizing convalescent mAbs with consequences on transmissibility provided other mutations within the S protein similarly promote cell fusion and viral entry.
Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , Anticorpos Monoclonais , COVID-19 , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/metabolismo , COVID-19/virologia , Humanos , Simulação de Dinâmica Molecular , Ligação ProteicaRESUMO
BACKGROUND: Despite an increased risk of fire in disadvantaged households, smoke alarm ownership is considerably lower than in the general population. The government currently recommends that local authorities install battery-operated smoke alarms in all public sector properties regardless of tenure. However, the extent to which local authorities comply is currently not known. We conducted a survey of local authorities to establish the extent of their smoke alarm provision to public sector households. METHODS: A telephone survey of all 405 local authorities within England and Wales was carried out. RESULTS: We obtained responses from 390 (97 per cent) local authorities, 266 of which had responsibility for housing. Over half of all public-sector households are offered smoke alarms by the local authorities. The majority of local authorities offer ionization and/or optical sensor alarm types (78 per cent), with many local authorities providing battery-operated alarms alone (17 per cent) or in combination with hardwired alarms (31 per cent). CONCLUSIONS: Many local authorities offer smoke alarm provision to their public-sector households. Whether this represents an effective and cost-effective use of resources requires further investigation.