Repurposing plant-derived substances as antivirals against sars-cov-2 / Redirecionando substâncias derivadas de plantas como antivirais contra Sars-cov-2

The urgent need for effective treatments for COVID-19 has developed, encouraging pharmaceutical companies to develop or redirect substances against SARS-CoV-2. Among them, substances used against worms, malaria, or bacteria were targeted to combat the virus. Such substances have been used in clinical trials and evaluated in vitro and in silico regarding the action on viral proteins, pharmacodynamics and toxicity of drugs. In this study, we conducted a systematic review of peer-reviewed articles involving molecules of plant origin with potential antiviral action on SARS-CoV-2. Reports containing the combinations of key words herbal, medicinal plants, natural products, and SARS-CoV-2 available from 01-01-2019 to 28-08-2020 in the Pubmed Central and World Wide Science sites were selected. A total of 677 items were retrieved. Of these, 170 were excluded because they were not complete, peer reviewed, freely, or related to vegetable products. Of the remaining, 345 were review articles, 23 were discussions, 4 were clinical trials, 14 showed in vitro experiments, and 121 were in silico studies. The proteins of SARS-CoV-2 considered as the therapeutic targets for the molecular docking were the structural spike glycoprotein (S protein), membrane protein Mpro, papain-like protease (PLpro), and RNA-dependent RNA polymerase (RdRp). Also, some studies have addressed the cell receptor ACE2 and natural products interaction. From in silico tests, therefore, 149 isolated plant molecules were identified with binding affinity to SARS-CoV-2 Mpro. Also, pharmacokinetic properties and bioavailability of some products were investigated highlighting the products nimbolide, withaferin-A, caffeic acid derivatives, rhamnetin, delta d-Viniferin, myri-citrin, chrysanthemin, myritilin, taiwanhomoflavone A, lactucopicrin 15-oxalate, nympholide A, afzelin, biorobin, herperidin and phyllaemblicin B, glycyrrhizic acid, and rutin. As reported, rutin may influence viral functional protein assembly and host inflammatory suppression. Its affinity for Mpro and toll like receptors (TLRs) besides in vivo results render rutin a potential novel therapeutic anti-coronavirus strategy. This study highlights the in silico diversity of plant metabolites with high potential of antiviral activity against SARS-CoV-2 as alternatives in the repurposing course against COVID-19 as well as other viral pandemics that may arise.The urgent need for effective treatments for COVID-19 has developed, encouraging pharmaceutical companies to develop or redirect substances against SARS-CoV-2. Among them, substances used against worms, malaria, or bacteria were targeted to combat the virus. Such substances have been used in clinical trials and evaluated in vitro and in silico regarding the action on viral proteins, pharmacodynamics and toxicity of drugs. In this study, we conducted a systematic review of peer-reviewed articles involving molecules of plant origin with potential antiviral action on SARS-CoV-2. Reports containing the combinations of key words herbal, medicinal plants, natural products, and SARS-CoV-2 available from 01-01-2019 to 28-08-2020 in the Pubmed Central and World Wide Science sites were selected. A total of 677 items were retrieved. Of these, 170 were excluded because they were not complete, peer reviewed, freely, or related to vegetable products. Of the remaining, 345 were review articles, 23 were discussions, 4 were clinical trials, 14 showed in vitro experiments, and 121 were in silico studies. The proteins of SARS-CoV-2 considered as the therapeutic targets for the molecular docking were the structural spike glycoprotein (S protein), membrane protein Mpro, papain-like protease (PLpro), and RNA-dependent RNA polymerase (RdRp). Also, some studies have addressed the cell receptor ACE2 and natural products interaction. From in silico tests, therefore, 149 isolated plant molecules were identified with binding affinity to SARS-CoV-2 Mpro. Also, pharmacokinetic properties and bioavailability of some products were investigated highlighting the products nimbolide, withaferin-A, caffeic acid derivatives, rhamnetin, delta d-Viniferin, myri-citrin, chrysanthemin, myritilin, taiwanhomoflavone A, lactucopicrin 15-oxalate, nympholide A, afzelin, biorobin, herperidin and phyllaemblicin B, glycyrrhizic acid, and rutin. As reported, rutin may influence viral functional protein assembly and host inflammatory suppression. Its affinity for Mpro and toll like receptors (TLRs) besides in vivo results render rutin a potential novel therapeutic anti-coronavirus strategy. This study highlights the in silico diversity of plant metabolites with high potential of antiviral activity against SARS-CoV-2 as alternatives in the repurposing course against COVID-19 as well as other viral pandemics that may arise

CLINICAL CHARACTERISTICS, OUTCOMES AND RISK FACTORS FOR DEATH AMONG CRITICALLY ILL PATIENTS WITH HIV-RELATED ACUTE KIDNEY INJURY

SUMMARY Background: The aim of this study is to describe clinical characteristics, outcomes and risk factors for death among patients with HIV-related acute kidney injury (AKI) admitted to an intensive care unit (ICU). Methods: A retrospective study was conducted with HIV-infected AKI patients admitted to the ICU of an infectious diseases hospital in Fortaleza, Brazil. All the patients with confirmed diagnosis of HIV and AKI admitted from January 2004 to December 2011 were included. A comparison between survivors and non-survivors was performed. Risk factors for death were investigated. Results: Among 256 AKI patients admitted to the ICU in the study period, 73 were identified as HIV-infected, with a predominance of male patients (83.6%), and the mean age was 41.2 ± 10.4 years. Non-survivor patients presented higher APACHE II scores (61.4 ± 19 vs. 38.6 ± 18, p = 0.004), used more vasoconstrictors (70.9 vs. 37.5%, p = 0.02) and needed more mechanical ventilation - MV (81.1 vs. 35.3%, p = 0.001). There were 55 deaths (75.3%), most of them (53.4%) due to septic shock. Independent risk factors for mortality were septic shock (OR = 14.2, 95% CI = 2.0-96.9, p = 0.007) and respiratory insufficiency with need of MV (OR = 27.6, 95% CI = 5.0-153.0, p < 0.001). Conclusion: Non-survivor HIV-infected patients with AKI admitted to the ICU presented higher severity APACHE II scores, more respiratory damage and hemodynamic impairment than survivors. Septic shock and respiratory insufficiency were independently associated to death

CLINICAL CHARACTERISTICS, OUTCOMES AND RISK FACTORS FOR DEATH AMONG CRITICALLY ILL PATIENTS WITH HIV-RELATED ACUTE KIDNEY INJURY

SUMMARY Background: The aim of this study is to describe clinical characteristics, outcomes and risk factors for death among patients with HIV-related acute kidney injury (AKI) admitted to an intensive care unit (ICU). Methods: A retrospective study was conducted with HIV-infected AKI patients admitted to the ICU of an infectious diseases hospital in Fortaleza, Brazil. All the patients with confirmed diagnosis of HIV and AKI admitted from January 2004 to December 2011 were included. A comparison between survivors and non-survivors was performed. Risk factors for death were investigated. Results: Among 256 AKI patients admitted to the ICU in the study period, 73 were identified as HIV-infected, with a predominance of male patients (83.6%), and the mean age was 41.2 ± 10.4 years. Non-survivor patients presented higher APACHE II scores (61.4 ± 19 vs. 38.6 ± 18, p = 0.004), used more vasoconstrictors (70.9 vs. 37.5%, p = 0.02) and needed more mechanical ventilation - MV (81.1 vs. 35.3%, p = 0.001). There were 55 deaths (75.3%), most of them (53.4%) due to septic shock. Independent risk factors for mortality were septic shock (OR = 14.2, 95% CI = 2.0-96.9, p = 0.007) and respiratory insufficiency with need of MV (OR = 27.6, 95% CI = 5.0-153.0, p < 0.001). Conclusion: Non-survivor HIV-infected patients with AKI admitted to the ICU presented higher severity APACHE II scores, more respiratory damage and hemodynamic impairment than survivors. Septic shock and respiratory insufficiency were independently associated to death

Influence of the ventilatory mode on acute adverse effects and facial thermography after noninvasive ventilation

ABSTRACT Objective: To compare the incidence and intensity of acute adverse effects and the variation in the temperature of facial skin by thermography after the use of noninvasive ventilation (NIV). Methods: We included 20 healthy volunteers receiving NIV via oronasal mask for 1 h. The volunteers were randomly divided into two groups according to the ventilatory mode: bilevel positive airway pressure (BiPAP) or continuous positive airway pressure (CPAP). Facial thermography was performed in order to determine the temperature of the face where it was in contact with the mask and of the nasal dorsum at various time points. After removal of the mask, the volunteers completed a questionnaire about adverse effects of NIV. Results: The incidence and intensity of acute adverse effects were higher in the individuals receiving BiPAP than in those receiving CPAP (16.1% vs. 5.6%). Thermographic analysis showed a significant cooling of the facial skin in the two regions of interest immediately after removal of the mask. The more intense acute adverse effects occurred predominantly among the participants in whom the decrease in the mean temperature of the nasal dorsum was lower (14.4% vs. 7.2%). The thermographic visual analysis of the zones of cooling and heating on the face identified areas of hypoperfusion or reactive hyperemia. Conclusions: The use of BiPAP mode was associated with a higher incidence and intensity of NIV-related acute adverse effects. There was an association between acute adverse effects and less cooling of the nasal dorsum immediately after removal of the mask. Cutaneous thermography can be an additional tool to detect adverse effects that the use of NIV has on facial skin