Flavonoid as possible therapeutic targets against COVID-19: a scoping review of in silico studies.

OBJECTIVES: This scoping review aims to present flavonoid compounds' promising effects and possible mechanisms of action on potential therapeutic targets in the SARS-CoV-2 infection process. METHODS: A search of electronic databases such as PubMed and Scopus was carried out to evaluate the performance of substances from the flavonoid class at different stages of SARS-CoV-2 infection. RESULTS: The search strategy yielded 382 articles after the exclusion of duplicates. During the screening process, 265 records were deemed as irrelevant. At the end of the full-text appraisal, 37 studies were considered eligible for data extraction and qualitative synthesis. All the studies used virtual molecular docking models to verify the affinity of compounds from the flavonoid class with crucial proteins in the replication cycle of the SARS-CoV-2 virus (Spike protein, PLpro, 3CLpro/ MPro, RdRP, and inhibition of the host's ACE II receptor). The flavonoids with more targets and lowest binding energies were: orientin, quercetin, epigallocatechin, narcissoside, silymarin, neohesperidin, delphinidin-3,5-diglucoside, and delphinidin-3-sambubioside-5-glucoside. CONCLUSION: These studies allow us to provide a basis for in vitro and in vivo assays to assist in developing drugs for the treatment and prevention of COVID-19.

Cost of Illness in Patients With COVID-19 Admitted in Three Brazilian Public Hospitals.

OBJECTIVES: The severity and transmissibility of COVID-19 justifies the need to identify the factors associated with its cost of illness (CoI). This study aimed to identify CoI, cost predictors, and cost drivers in the management of patients with COVID-19 from hospital and Brazil's Public Health System (SUS) perspectives. METHODS: This is a multicenter study that evaluated the CoI in patients diagnosed of COVID-19 who reached hospital discharge or died before being discharged between March and September 2020. Sociodemographic, clinical, and hospitalization data were collected to characterize and identify predictors of costs per patients and cost drivers per admission. RESULTS: A total of 1084 patients were included in the study. For hospital perspective, being overweight or obese, being between 65 and 74 years old, or being male showed an increased cost of 58.4%, 42.9%, and 42.5%, respectively. From SUS perspective, the same predictors of cost per patient increase were identified. The median cost per admission was estimated at US$359.78 and US$1385.80 for the SUS and hospital perspectives, respectively. In addition, patients who stayed between 1 and 4 days in the intensive care unit (ICU) had 60.9% higher costs than non-ICU patients; these costs significantly increased with the length of stay (LoS). The main cost driver was the ICU-LoS and COVID-19 ICU daily for hospital and SUS perspectives, respectively. CONCLUSIONS: The predictors of increased cost per patient at admission identified were overweight or obesity, advanced age, and male sex, and the main cost driver identified was the ICU-LoS. Time-driven activity-based costing studies, considering outpatient, inpatient, and long COVID-19, are needed to optimize our understanding about cost of COVID-19.

Bioactive compounds as potential angiotensin-converting enzyme II inhibitors against COVID-19: a scoping review.

OBJECTIVE AND DESIGN: The current study aimed to summarize the evidence of compounds contained in plant species with the ability to block the angiotensin-converting enzyme 2 (ACE-II), through a scoping review. METHODS: PubMed and Scopus electronic databases were used for the systematic search and a manual search was performed RESULTS: Studies included were characterized as in silico. Among the 200 studies retrieved, 139 studies listed after the exclusion of duplicates and 74 were included for the full read. Among them, 32 studies were considered eligible for the qualitative synthesis. The most evaluated class of secondary metabolites was flavonoids with quercetin and curcumin as most actives substances and terpenes (isothymol, limonin, curcumenol, anabsinthin, and artemisinin). Other classes that were also evaluated were alkaloid, saponin, quinone, substances found in essential oils, and primary metabolites as the aminoacid L-tyrosine and the lipidic compound 2-monolinolenin. CONCLUSION: This review suggests the most active substance from each class of metabolites, which presented the strongest affinity to the ACE-II receptor, what contributes as a basis for choosing compounds and directing the further experimental and clinical investigation on the applications these compounds in biotechnological and health processes as in COVID-19 pandemic.

The naturally-derived alkaloids as a potential treatment for COVID-19: A scoping review.

Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which has a high mortality rate and transmissibility. In this context, medicinal plants have attracted attention due to the wide availability and variety of therapeutic compounds, such as alkaloids, a vast class with several proven pharmacological effects, like the antiviral and anti-inflammatory activities. Therefore, this scoping review aimed to summarize the current knowledge of the potential applicability of alkaloids for treating COVID-19. A systematic search was performed on PubMed and Scopus, from database inception to August 2021. Among the 63 eligible studies, 65.07% were in silico model, 20.63% in vitro and 14.28% clinical trials and observational studies. According to the in silico assessments, the alkaloids 10-hydroxyusambarensine, cryptospirolepine, crambescidin 826, deoxynortryptoquivaline, ergotamine, michellamine B, nigellidine, norboldine and quinadoline B showed higher binding energy with more than two target proteins. The remaining studies showed potential use of berberine, cephaeline, emetine, homoharringtonine, lycorine, narciclasine, quinine, papaverine and colchicine. The possible ability of alkaloids to inhibit protein targets and to reduce inflammatory markers show the potential for development of new treatment strategies against COVID-19. However, more high quality analyses/reviews in this field are necessary to firmly establish the effectiveness/safety of the alkaloids here described.