45 research outputs found
Could Nanotheranostics be the Answer to the Coronavirus Crisis?
The COVID-19 pandemic is expanding worldwide. This pandemic associated with COVID-19 placed the spotlight on how bacterial (e.g., methicillin-resistant Staphylococcus aureus) co-infections may impact responses to coronavirus. In this review the ways in which nanoparticles can contain and rapidly diagnose COVID-19 under the umbrella of nanotheranostics (i.e., smart, single agents combining nanodiagnostics and nanotherapeutics) are elaborated. The present work provides new insights into the promising incorporation of antiviral nanotheranostics into nanostructured materials, including electrospun fibers with tailored pore sizes and hydrophobicity, namely "superhydrophobic self-disinfecting electrospun facemasks/fabrics (SSEF)." SSEFs are proposed as smart alternatives to address the drawbacks of N95 respirators. The challenges of coronavirus containment are underscored, literature is reviewed, and "top-five suggestions" for containing COVID-19 are offered, including: i) preventive appraisals-avoiding needless hospital admission and practicing frequent hand washing (from 20 to 60 s). ii) Diagnostics-highly recommending nanodiagnostics, detecting COVID-19 within 10 min. iii) Therapeutics-expanding nanotherapeutics to treat COVID-19 and bacterial co-infections after safety assessments and clinical trials. iv) Multipronged and multinational, including China, collaborative appraisals. v) Humanitarian compassion to traverse this pandemic in a united way.Peer reviewe
Escape of SARS-CoV-2 501Y.V2 from neutralization by convalescent plasma
SARS-CoV-2 variants of concern (VOC) have arisen independently at multiple locations [1, 2] and may reduce the efficacy of current vaccines targeting the spike glycoprotein [3]. Here, using a live virus neutralization assay (LVNA), we compared neutralization of a non-VOC variant versus the 501Y.V2 variant using plasma collected from adults hospitalized with COVID-19 from two South African infection waves, with the second wave dominated by 501Y.V2 infections. Sequencing demonstrated that infections in first wave plasma donors were with viruses harbouring none of the 501Y.V2-defining mutations, except for one with the E484K mutation in the receptor binding domain. 501Y.V2 virus was effectively neutralized by plasma from second wave infections and first wave virus was effectively neutralized by first wave plasma. In cross-neutralization, 501Y.V2 virus was poorly neutralized by first wave plasma, with a 15.1-fold drop relative to 501Y.V2 neutralization by second wave plasma across participants. In contrast, second wave plasma cross-neutralization of first wave virus was more effective, showing only a 2.3-fold decline relative to first wave plasma neutralization of first wave virus. While we only tested one plasma elicited by E484K alone, this potently neutralized both variants. The observed effective neutralization of first wave virus by 501Y.V2 infection elicited plasma provides preliminary evidence that vaccines based on VOC sequences could retain activity against other circulating SARS-CoV-2 lineages
SARS-CoV-2 prolonged infection during advanced HIV disease evolves extensive immune escape
Characterizing SARS-CoV-2 evolution in specific geographies may help predict properties of the variants that come from these regions. We mapped neutralization of a SARS-CoV-2 strain that evolved over 6Â months from ancestral virus in a person with advanced HIV disease in South Africa; this person was infected prior to emergence of the Beta and Delta variants. We longitudinally tracked the evolved virus and tested it against self-plasma and convalescent plasma from ancestral, Beta, and Delta infections. Early virus was similar to ancestral, but it evolved a multitude of mutations found in Omicron and other variants. It showed substantial but incomplete Pfizer BNT162b2 escape, weak neutralization by self-plasma, and despite pre-dating Delta, it also showed extensive escape of Delta infection-elicited neutralization. This example is consistent with the notion that SARS-CoV-2 evolving in individual immune-compromised hosts, including those with advanced HIV disease, may gain immune escape of vaccines and enhanced escape of Delta immunity, and this has implications for vaccine breakthrough and reinfections
Selection analysis identifies unusual clustered mutational changes in Omicron lineage BA.1 that likely impact Spike function.
Among the 30 non-synonymous nucleotide substitutions in the Omicron S-gene are 13 that have only rarely been seen in other SARS-CoV-2 sequences. These mutations cluster within three functionally important regions of the S-gene at sites that will likely impact (i) interactions between subunits of the Spike trimer and the predisposition of subunits to shift from down to up configurations, (ii) interactions of Spike with ACE2 receptors, and (iii) the priming of Spike for membrane fusion. We show here that, based on both the rarity of these 13 mutations in intrapatient sequencing reads and patterns of selection at the codon sites where the mutations occur in SARS-CoV-2 and related sarbecoviruses, prior to the emergence of Omicron the mutations would have been predicted to decrease the fitness of any genomes within which they occurred. We further propose that the mutations in each of the three clusters therefore cooperatively interact to both mitigate their individual fitness costs, and adaptively alter the function of Spike. Given the evident epidemic growth advantages of Omicron over all previously known SARS-CoV-2 lineages, it is crucial to determine both how such complex and highly adaptive mutation constellations were assembled within the Omicron S-gene, and why, despite unprecedented global genomic surveillance efforts, the early stages of this assembly process went completely undetected