While emergence of new SAS-COV-2 variants is posing grave challenge to efforts to deal with the COVID-19 pandemic, the structural and molecular basis of their fitness remain poorly understood. We performed in silico analysis of structures of two most frequent SARS-COV-2 mutations, namely, N501Y and E484K, to identify plausible basis of their fitness over the original strain. The analysis suggested that the N501Y mutation is associated with strengthening of intra- as well as intermolecular H-bond in the hACE2 receptor-spike protein complex, which could result in increased affinity and, therefore, higher infectivity. While E484K mutation did not seem to directly affect the binding with hACE2 receptor, it disrupted H-bonding and salt-bridge interaction associated with binding with neutralizing antibody, which could affect chance of re-infection, disease outcome. Survey of several other mutations showing reduction in antibody-mediated neutralization also revealed that similar disruption of H-bonding or salt-bridge or Van der Waals interaction might explain their phenotype. Analysis of GESS database indicated that N501Y, EK484 as well as these other mutations existed since March-April, 2020, might have evolved independently across the world and may keep accumulating, which could affect efficacy of vaccination and antibody-based therapies. Our analysis also indicated that these may spread in spite of current travel restrictions focused on few countries and evolve indigenously warranting intensification of surveillance for emerging mutations among all travellers as well as people in their dwelling zones. Meta-analysis of existing literature showed that repeat testing of travellers, contacts and others under scrutiny 7-11 days after the initial RT-PCR test may significantly help to contain the spread of emerging variants by catching false negative results. In addition, existing evidence calls for development of strain-specific tests, escalated sequencing and broadening the scope of surveillance including in hospitals and animal farms to contain the threat of emerging variants.
Use of face mask has become an integral part of public life in the post-pandemic era. However, the understanding of the effect of wearing mask on physiology remains incomplete and is required for informing public health policies. Earlier studies indicated changes in breath and blood gas composition upon wearing FFP2 mask. For the first time, we report analysis of the effect of wearing FFP2 mask on metabolic composition of saliva, a proximal matrix to breath. Un-induced saliva was collected from healthy volunteers (n =10) before and after wearing FFP2 mask for 30 minutes and analyzed. Results showed that such short-term mask use did not cause any significant change in heart rate, pulse rate and SpO2. The individuality of overall salivary metabotype was found to be robust and unaffected by mask use. There were marginal increases in relative abundances of L-fucose, 5-aminovaleric acid, putrescine, phloretic acid and benzenepropionic acid. Results indicated that while there were no adverse changes in physiological parameters and salivary metabotype, mask use was associated with changes in microbial metabolic activity. Consequences of such changes remain to be examined. However, these might explain change in odour perception that was reported to be associated with mask use.
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