Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.7 and B.1.351 variants were first identified in the United Kingdom and South Africa, respectively, and have since spread to many ...countries. These variants harboring diverse mutations in the gene encoding the spike protein raise important concerns about their immune evasion potential. Here, we isolated infectious B.1.1.7 and B.1.351 strains from acutely infected individuals. We examined sensitivity of the two variants to SARS-CoV-2 antibodies present in sera and nasal swabs from individuals infected with previously circulating strains or who were recently vaccinated, in comparison with a D614G reference virus. We utilized a new rapid neutralization assay, based on reporter cells that become positive for GFP after overnight infection. Sera from 58 convalescent individuals collected up to 9 months after symptoms, similarly neutralized B.1.1.7 and D614G. In contrast, after 9 months, convalescent sera had a mean sixfold reduction in neutralizing titers, and 40% of the samples lacked any activity against B.1.351. Sera from 19 individuals vaccinated twice with Pfizer Cominarty, longitudinally tested up to 6 weeks after vaccination, were similarly potent against B.1.1.7 but less efficacious against B.1.351, when compared to D614G. Neutralizing titers increased after the second vaccine dose, but remained 14-fold lower against B.1.351. In contrast, sera from convalescent or vaccinated individuals similarly bound the three spike proteins in a flow cytometry-based serological assay. Neutralizing antibodies were rarely detected in nasal swabs from vaccinees. Thus, faster-spreading SARS-CoV-2 variants acquired a partial resistance to neutralizing antibodies generated by natural infection or vaccination, which was most frequently detected in individuals with low antibody levels. Our results indicate that B1.351, but not B.1.1.7, may increase the risk of infection in immunized individuals.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19). It emerged from China in December 2019 and rapidly spread across the globe, ...causing a pandemic with unprecedented impacts on public health and economy. Therefore, there is an urgent need for the development of curative treatments and vaccines. In humans, COVID-19 pathogenesis shows a wide range of symptoms, from asymptomatic to severe pneumonia. Identifying animal models of SARS-CoV-2 infection that reflect the clinical symptoms of COVID-19 is of critical importance. Nonhuman primates (NHPss) correspond to relevant models to assess vaccine and antiviral effectiveness. This review discusses the use of NHPs as models for COVID-19 research, with focus on the pathogenesis of SARS-CoV-2 infection, drug discovery and pre-clinical evaluation of vaccine candidates.
Severe COVID‐19 is characterized by lung abnormalities, including the presence of syncytial pneumocytes. Syncytia form when SARS‐CoV‐2 spike protein expressed on the surface of infected cells ...interacts with the ACE2 receptor on neighboring cells. The syncytia forming potential of spike variant proteins remain poorly characterized. Here, we first assessed Alpha (B.1.1.7) and Beta (B.1.351) spread and fusion in cell cultures, compared with the ancestral D614G strain. Alpha and Beta replicated similarly to D614G strain in Vero, Caco‐2, Calu‐3, and primary airway cells. However, Alpha and Beta formed larger and more numerous syncytia. Variant spike proteins displayed higher ACE2 affinity compared with D614G. Alpha, Beta, and D614G fusion was similarly inhibited by interferon‐induced transmembrane proteins (IFITMs). Individual mutations present in Alpha and Beta spikes modified fusogenicity, binding to ACE2 or recognition by monoclonal antibodies. We further show that Delta spike also triggers faster fusion relative to D614G. Thus, SARS‐CoV‐2 emerging variants display enhanced syncytia formation.
SYNOPSIS
The spike protein of the novel SARS‐CoV‐2 variants are comparative more fusogenic than the earlier strains. The mutations in the variant spike protein modulate syncytia formation, ACE2 binding, and antibody escape.
The spike protein of Alpha, Beta and Delta, in the absence of other viral proteins, induce more syncytia than the ancestral D614G strain.
The ACE2 affinity of the variant spike proteins correlates to their fusogenicity.
Variant associated mutations P681H, D1118H, and D215G augment cell‐cell fusion, while antibody escape mutation E484K, K417N and Δ242‐244 hamper it.
Spike protein mutations expressed by emerging SARS‐CoV‐2 variants‐of‐concern differentially affect host cell‐to‐cell fusion, ACE2 receptor binding, and antibody escape.
Seafood is the world's most internationally traded food commodity. Approximately three out of every seven people globally rely on seafood as a primary source of animal protein (1). Revelations about ...slavery and labor rights abuses in fisheries have sparked outrage and shifted the conversation (2, 3), placing social issues at the forefront of a sector that has spent decades working to improve environmental sustainability. In response, businesses are seeking to reduce unethical practices and reputational risks in their supply chains. Governments are formulating policy responses, and nonprofit and philanthropic organizations are deploying resources and expertise to address critical social issues. Yet the scientific community has not kept pace with concerns for social issues in the sector. As the United Nations Ocean Conference convenes in New York (5 to 9 June), we propose a framework for social responsibility and identify key steps the scientific community must take to inform policy and practice for this global challenge.
This double-blind study investigated the effects of vitamin and mineral complex supplementation on the neuromuscular function of the knee-extensor muscles after a prolonged trail running race.
...Twenty-two well-trained endurance runners took either placebo (Pl group) or vitamins and minerals (Vm group) for 21 d before the race and for 2 d after the race. Maximal voluntary contractions (MVC) and surface EMG activity of the vastus lateralis (VL) muscle were recorded before (pre) and 1 h (post), 24 h (post 24) and 48 h (post 48) after the race. Central activation ratio (CAR), neural (M-wave), and contractile (muscular twitch) properties of the quadriceps muscles were analyzed using electrical stimulation techniques.
The knee-extensor MVC was significantly (P < 0.01) reduced after exercise for both groups (Vm: 36.5 +/- 3.0 %; Pl: 36.9 +/- 2.1%), but MVC recovery was greater for Vm than Pl after 48 h (11%, P < 0.05). The reduced MVC after exercise was associated with a significant reduction in maximal EMG normalized to the M-wave in VL muscle and in CAR for both groups. Characteristics of the muscular twitch were not significantly altered for either groups, whereas M-wave duration increased significantly (P < 0.05) after exercise.
The reduction of MVC immediately after the race appeared to result from peripheral mechanisms such as a failure in muscle membrane excitation and, to a lesser extent, from reduced central activation. The cause of the depressed MVC 24 h after the race seemed to be located within the muscle itself. A dietary supplementation of a vitamin and mineral complex does not attenuate the loss of contractile function immediately after the running exercise, and it may accelerate the recovery of maximal force capacity.
HHV-6 has been implicated in a number of neurological disorders. Recent evidence has suggested high incidence of HHV-6 infection in patients (46%) undergoing allogeneic bone marrow transplant (BMT).
...To investigate whether HHV-6 plays a role in the development of fatal encephalopathy in an allogeneic post-BMT patient using an unbiased approach.
Detection of HHV-6 viral DNA sequence and RNA expression were demonstrated in fresh frozen post-mortem autopsy material derived from the insular cortex using a multi-virus array platform. In addition, PCR analysis by real-time quantitative TaqMan demonstrated high viral burden in multiple brain regions tested. Sequencing analysis of PCR product confirmed the virus to be HHV-6 variant B.
Active infection as demonstrated by expression of viral RNA and high viral load in the CNS suggest a possible pathogenic role of HHV-6 in development neurologic complications post-BMT.
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