RESUMEN
In this study, the grain growth behaviour of ZnO-V2O5-based ceramics with 0.25-0.75 mol% additions of PrMnO3 was systematically investigated during sintering from 850 °C to 925 °C. with the aim to control the ZnO grain size for their application as varistors. It was found that with the increased addition of PrMnO3, in addition to the decrease in the average grain size, the grain size distribution also narrowed and eventually changed from a bimodal to unimodal distribution after a 0.75 mol% PrMnO3 addition. The grain growth control was achieved by a pinning effect of the secondary ZnCr2O4 and PrVO4 phases at the ZnO grain boundaries. The apparent activation energy of the ZnO grain growth in these ceramics was found to increase with increased additions of PrVO4, hence the observed reduction in the ZnO grain sizes.
RESUMEN
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the host cell after the receptor binding domain (RBD) of the virus spike (S) glycoprotein binds to the human angiotensin-converting enzyme 2 (hACE2). This binding requires the RBD to undergo a conformational change from a closed to an open state. In the present study, a key pair of salt bridges formed by the side chains of K537 and E619, residues at the interfaces of SD1 and SD2, respectively, was identified to promote the opening of the RBD. Mutations of K537Q and E619D reduced their side chain lengths and eliminated this pair of salt bridges; as a result, the opening of the RBD was not observed in the MD simulations. Thus, blocking the formation of this pair of salt bridges is a promising approach for treating novel coronavirus disease 2019 (COVID-19). FDA approved drug molecules were screened by their capabilities of blocking the formation of the key pair of salt bridges, achieved by their positional stabilities in the cavity containing the side chains of K537 and E619 formed in the interface between SD1 and SD2. Simeprevir, imatinib, and naldemedine were identified to possess the desired capability with the most favorable interaction energies.
Asunto(s)
Antivirales/farmacología , Diseño de Fármacos , SARS-CoV-2/efectos de los fármacos , Glicoproteína de la Espiga del Coronavirus/antagonistas & inhibidores , Antivirales/química , Evaluación Preclínica de Medicamentos , Humanos , Mesilato de Imatinib/química , Mesilato de Imatinib/farmacología , Simulación del Acoplamiento Molecular , Naltrexona/análogos & derivados , Naltrexona/química , Naltrexona/farmacología , Dominios Proteicos/efectos de los fármacos , SARS-CoV-2/química , Simeprevir/química , Simeprevir/farmacología , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/metabolismoRESUMEN
Correction for 'Antiviral drug design based on the opening mechanism of spike glycoprotein in SARS-CoV-2' by Ruichao Mao et al., Phys. Chem. Chem. Phys., 2021, DOI: 10.1039/d1cp01045j.
