A novel insight on SARS-CoV-2 S-derived fragments in the control of the host immunity (preprint)

Despite all efforts to combat the pandemic of COVID-19, we are still living with high numbers of infected persons, an overburdened health care system, and the lack of an effective and definitive treatment. Understanding the pathophysiology of the disease is crucial for the development of new technologies and therapies for the best clinical management of patients. Since the manipulation of the whole virus requires a structure with an adequate level of biosafety, the development of alternative technologies, such as the synthesis of peptides from viral proteins, is a possible solution to circumvent this problem. In addition, the use and validation of animal models is of extreme importance to screen new drugs and to compress the organism's response to the disease. Peptides derived from recombinant S protein from SARS-CoV-2 were synthesized and validated by in silico, in vitro and in vivo methodologies. Macrophages and neutrophils were challenged with the peptides and the production of inflammatory mediators and activation profile were evaluated. These peptides were also inoculated into the swim bladder of transgenic zebrafish larvae at 6 days post fertilization to mimic the inflammatory process triggered by the virus, which was evaluated by confocal microscopy. In addition, toxicity and oxidative stress assays were also developed. In silico and molecular dynamics assays revealed that the peptides bind to the ACE2 receptor stably and interact with receptors and adhesion molecules, such as MHC and TCR, from humans and zebrafish. Macrophages stimulated with one of the peptides showed increased production of NO, TNF-α and CXCL2. Inoculation of the peptides in zebrafish larvae triggered an inflammatory process marked by macrophage recruitment and increased mortality, as well as histopathological changes, similarly to what is observed in individuals with COVID-19. The use of peptides is a valuable alternative for the study of host immune response in the context of COVID-19. The use of zebrafish as an animal model also proved to be appropriate and effective in evaluating the inflammatory process, comparable to humans.

Immunization with SARS-CoV-2 nucleocapsid protein triggers a pulmonary immune response in rats (preprint)

ABSTRACT The SARS-CoV-2 pandemic have been affecting millions of people worldwide, since the beginning of 2020. COVID-19 can cause a wide range of clinical symptoms, which varies from asymptomatic presentation to severe respiratory insufficiency, exacerbation of immune response, disseminated microthrombosis and multiple organ failure, which may lead to dead. Due to the rapid spread of SARS-CoV-2, the development of vaccines to minimize COVID-19 severity in the world population is imperious. One of the employed techniques to produce vaccines against emerging viruses is the synthesis of recombinant proteins, which can be used as immunizing agents. Based on the exposed, the aim of the present study was to verify the systemic and immunological effects of IM administration of recombinant Nucleocapsid protein (NP), derived from SARS-CoV-2 and produced by this research group, in 2 different strains of rats ( Rattus norvegicus ); Wistar and Lewis. For this purpose, experimental animals received 4 injections of NP, once a week, and were submitted to biochemical and histological analysis. Our results showed that NP inoculations were safe for the animals, which presented no clinical symptoms of worrying side effects, nor laboratorial alterations in the main biochemical and histological parameters, suggesting the absence of toxicity induced by NP. Moreover, NP injections successfully triggered the production of specific anti-SARS-CoV-2 IgG antibodies by both Wistar and Lewis rats, showing the sensitization to have been well sufficient for the immunization of these strains of rats. Additionally, we observed the local lung activation of the Bronchus-Associated Lymphoid Tissue (BALT) of rats in the NP groups, suggesting that NP elicits specific lung immune response. Although pre-clinical and clinical studies are still required, our data support the recombinant NP produced by this research group as a potential immunizing agent for massive vaccination, and may represent advantages upon other recombinant proteins, since it seems to induce specific pulmonary protection.

Remote home-based resistance exercise acutely improves mood profile in older individuals under social isolation during the COVID-19 pandemic (preprint)

Purpose To assess the effect of a remote home-based resistance exercise session on mood profile in older individuals under social isolation during coronavirus 19 disease (COVID-19) pandemic.Methods 32 older individuals (20 women; age = 67.7 ± 6.4 y) who interrupted their regular physical activity routine during the COVID-19 pandemic participated in a remote home-based exercise session via video call. The Brunel Mood Scale (BRUMS) questionnaire was applied one day before and immediately after a body weight exercise session (three sets of 15 to 30 reps in six exercises) to evaluate participants’ mood state.Results Significant post-exercise reductions (P < 0.05) were found in tension (41.2 ± 8.1), depression (61.7 ± 41.8 %), anger (81.2 ± 66.2 %) and mental confusion (42,9 ± 33.1 %), while a significant post-exercise increase (P = 0.023) was found in vigor (18.5 ± 5.1 %). No significant difference between pre- and post-exercise was found in fatigue. The pos-exercise changes on mood state factors resulted in significant reduction (P = 0.032) on total mood disorder score (20.2 ± 11.1 %) after exercise.Conclusion A remote home-based resistance exercise session was effective to improve mood profile in older individuals under social isolation during COVID-19 pandemic.

An insight into neurotoxic and toxicity of spike fragments SARS-CoV-2 by exposure environment: A threat to aquatic health? (preprint)

The Spike protein (S protein) is a critical component in the infection of the new coronavirus (SARS-CoV-2). The objective of this work was to evaluate whether peptides from S protein could cause negative impact in the aquatic animals. The aquatic toxicity of SARS-CoV-2 spike protein peptides derivatives has been evaluated in tadpoles (n = 50 tadpoles / 5 replicates of 10 animals) from species Physalaemus cuvieri (Leptodactylidae). After synthesis, purification, and characterization of peptides (PSDP2001, PSDP2002, PSDP2003) an aquatic contamination has been simulatedwith these peptides during 24 hours of exposure in two concentrations (100 and 500 ng/mL). The control group ("C") was composed of tadpoles kept in polyethylene containers containing de-chlorinated water. Oxidative stress, antioxidant biomarkers and neurotoxicity activity were assessed. In both concentrations, PSPD2002 and PSPD2003 increased catalase and superoxide dismutase antioxidants enzymes activities, as well as oxidative stress (nitrite levels, hydrogen peroxide and reactive oxygen species). All three peptides also increased acetylcholinesterase activity in the highest concentration. These peptides showed molecular interactions in silico with acetylcholinesterase and antioxidant enzymes. Aquatic particle contamination of SARS-CoV-2 has neurotoxics effects in P. cuvieri tadpoles. These findings indicate that the COVID-19 can constitute environmental impact or biological damage potential. HIGHLIGHTSO_LISARS-CoV-2 spike protein peptides (PSDP) were synthesized, purified, and characterized by solid phase peptide synthesis. C_LIO_LIPSDP peptides promoted REDOX imbalance and acute neurotoxicity in tadpoles (Physalaemus cuvieri) C_LIO_LIIn silico studies have shown interactionsbetween peptides and acetylcholinesterase and antioxidant enzymes C_LIO_LIAquatic particle contamination of SARS-CoV-2 can constitute additional environmental damage C_LI GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=106 SRC="FIGDIR/small/425914v1_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@1b99c31org.highwire.dtl.DTLVardef@bd6d71org.highwire.dtl.DTLVardef@5c37f2org.highwire.dtl.DTLVardef@5d027d_HPS_FORMAT_FIGEXP M_FIG C_FIG

Home confinement during COVID-19 pandemic reduced physical activity but not health-related quality of life in previously active older women (preprint)

Background: To investigate the effect of COVID-19 home confinement on levels of physical activity, sedentary behavior and health-related quality of life (HRQL) in older women previously participating in exercise and educational programs. Methods: 64 older women (age = 72{+/-}5 ys) who participated in a physical exercise/educational program and adhered to government home confinement recommendations have their levels of physical activity, sedentary behavior and HRQL assessed before and during (11 to 13 weeks after introduction of government recommendations to reduce virus transmission) COVID-19 pandemic. Results: There were significant reductions in total physical activity (-259 METs/week, P = 0.02), as a result of a ~17.0 % reduction in walking (-30.8 min/week, P = 0.004) and ~41.8 % reduction in vigorous-intensity activity (-29.6 min/week, P < 0.001). Sedentary behavior also increased (2.24 h/week, P < 0.001; 1.07 h/week days, P < 0.001; and 1.54 h/weekend days, P < 0.001). However, no significant change occurred in moderate-intensity physical activity, and HRQL domains and facets, except for an improvement in environment domain. Conclusion: Home confinement due to COVID-19 pandemic decreased levels of physical activity and increased levels of sedentary behavior in previously active older women who participated in an educational program. However, there were no significant changes in HRQL. These results suggest that educational programs promoting healthy behaviors may attenuate the impact of home confinement in older women.