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Paula Andrea Velásquez,1,2 Juan C Hernandez,1,2 Elkin Galeano,3 Jaime Hincapié-García,4 María Teresa Rugeles,2 Wildeman Zapata-Builes1,2 1Grupo Infettare, Facultad de Medicina, Universidad Cooperativa de Colombia, Medellín, Colombia; 2Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Medellín, Colombia; 3Grupo Productos Naturales Marinos, Departamento de Farmacia, Facultad de Ciencias Farmacéuticas y Alimentarias, Universidad de Antioquia UdeA, Medellín, Colombia; 4Grupo de investigación, Promoción y prevención farmacéutica, Facultad de Ciencias Farmacéuticas y Alimentarias, Universidad de Antioquia UdeA, Medellín, ColombiaCorrespondence: Wildeman Zapata-Builes, Grupo Infettare, Facultad de Medicina Universidad Cooperativa de Colombia, Calle 50 # 40-74, Medellín, Colombia, Tel +57-4 4446065, Ext 4252, Email wildeman.zapatab@campusucc.edu.coAbstract: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a betacoronavirus responsible for the COVID-19 pandemic, causing respiratory disorders, and even death in some individuals, if not appropriately treated in time. To face the pandemic, preventive measures have been taken against contagions and the application of vaccines to prevent severe disease and death cases. For the COVID-19 treatment, antiviral, antiparasitic, anticoagulant and other drugs have been reused due to limited specific medicaments for the disease. Drug repurposing is an emerging strategy with therapies that have already tested safe in humans. One promising alternative for systematic experimental screening of a vast pool of compounds is computational drug repurposing (in silico assay). Using these tools, new uses for approved drugs such as chloroquine, hydroxychloroquine, ivermectin, zidovudine, ribavirin, lamivudine, remdesivir, lopinavir and tenofovir/emtricitabine have been conducted, showing effectiveness in vitro and in silico against SARS-CoV-2 and some of these, also in clinical trials. Additionally, therapeutic options have been sought in natural products (terpenoids, alkaloids, saponins and phenolics) with promising in vitro and in silico results for use in COVID-19 disease. Among these, the most studied are resveratrol, quercetin, hesperidin, curcumin, myricetin and betulinic acid, which were proposed as SARS-CoV-2 inhibitors. Among the drugs reused to control the SARS-CoV2, better results have been observed for remdesivir in hospitalized patients and outpatients. Regarding natural products, resveratrol, curcumin, and quercetin have demonstrated in vitro antiviral activity against SARS-CoV-2 and in vivo, a nebulized formulation has demonstrated to alleviate the respiratory symptoms of COVID-19. This review shows the evidence of drug repurposing efficacy and the potential use of natural products as a treatment for COVID-19. For this, a search was carried out in PubMed, SciELO and ScienceDirect databases for articles about drugs approved or under study and natural compounds recognized for their antiviral activity against SARS-CoV-2.Keywords: COVID-19, pandemic, coronavirus, medicinal plants

This article evaluated the in vitro antiviral effect of atorvastatin (ATV) against SARS-CoV-2 and identified the interaction affinity between this compound and two SARS-CoV-2 proteins. The antiviral activity of atorvastatin against this virus was evaluated by three different treatment strategies [(i) pre-post treatment, (ii) pre-infection treatment, and (iii) post-infection treatment] using Vero E6 and Caco-2 cells. The interaction of atorvastatin with RdRp (RNA-dependent RNA polymerase) and 3CL protease (3-chymotrypsin-like protease) was evaluated by molecular docking. The CC50s (half-maximal cytotoxic concentrations) obtained for ATV were 50.3 and 64.5 μM in Vero E6 and Caco-2, respectively. This compound showed antiviral activity against SARS-CoV-2 D614G strain in Vero E6 with median effective concentrations (EC50s) of 15.4, 12.1, and 11.1 μM by pre-post, pre-infection, and post-infection treatments, respectively. ATV also inhibited Delta and Mu variants by pre-post treatment (EC50s of 16.8 and 21.1 μM, respectively). In addition, ATV showed an antiviral effect against the D614G strain independent of the cell line (EC50 of 7.4 μM in Caco-2). The interaction of atorvastatin with SARS-CoV-2 RdRp and 3CL protease yielded a binding affinity of -6.7 kcal/mol and -7.5 kcal/mol, respectively. Our study demonstrated the in vitro antiviral activity of atorvastatin against the ancestral SARS-CoV-2 D614G strain and two emerging variants (Delta and Mu), with an independent effect of the cell line. A favorable binding affinity between ATV and viral proteins by bioinformatics methods was found. Due to the extensive clinical experience of atorvastatin use, it could prove valuable in the treatment of COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zapata-Cardona, Flórez-Álvarez, Zapata-Builes, Guerra-Sandoval, Guerra-Almonacid, Hincapié-García, Rugeles and Hernandez.)

Objective: We assessed maternal and perinatal outcomes in pregnant women with type 1 diabetes, treated with continuous subcutaneous insulin infusion and real time continuous glucose monitoring., Methods: This is a retrospective study, analyzing the basal characteristics, glycemic control, maternal and perinatal outcomes of pregnant women with type 1 diabetes, who were on an insulin pump with continuous glucose monitoring between 2011 and 2015., Results: Fourteen patients were included. The median age was 33 and disease duration 12 years. Indications for therapy were mainly poor glycemic control and severe hypoglycemia. The median A1c decrease was 1.02% between the first and third trimester. Pregnancies were associated with complications: 7.1% of the patients had diabetic ketoacidosis, 7.1% had an abortion, 28.5% gestational hypertension and 12.2% preeclampsia. The median gestational age at birth was 37 weeks and four days; the frequency of preterm birth was 7.1% and macrosomia 21.4%. There were no congenital malformations or perinatal death., Conclusions: Baseline characteristics and results of patients in this study were similar to those reported in the previous literature. Continuous subcutaneous insulin infusion with continuous glucose monitoring is an alternative treatment option for pregnant women with type 1 diabetes before or during pregnancy.

Objective: To describe baseline characteristics of diabetic patients who were started on insulin pump and real time continuous glucose monitor (CSII-rtCGM) in a specialized center in Medellin, Colombia., Materials and Methods: All patients with diabetes with complete data who were started on CSII-rtCGM between February 2010 and May 2014 were included. This is a descriptive analysis of the sociodemographic and clinical characteristics., Results: 141 of 174 patients attending the clinic were included. 90,1% had type 1diabetes (T1D). The average age of T1D patients at the beginning of therapy was 31,4 years (SD 14,1). 75.8% of patients had normal weight (BMI<25), 21.0% were overweight (BMI 25-30) and 2,3% were obese (BMI>30). The median duration of T1D was 13 years (P25-P75=10.7-22.0). 14,2% of the patients were admitted at least once in the year preceding the start of CSII-rtCGM because of diabetes related complications. Mean A1c was 8.6%±1.46%. The main reasons for starting CSII-rtCGM were: poor glycemic control (50.2%); frequent hypoglycemia, nocturnal hypoglycemia, hypoglycemia related to exercise, asymptomatic hypoglycemia (30.2%); severe hypoglycemia (16.44%) and dawn phenomena (3.1%)., Conclusion: Baseline characteristics of patients included in this study who were started on CSII-rtCGM are similar to those reported in the literature. The Clinic starts CSII-rtCGM mainly in T1D patients with poor glycemic control, frequent or severe hypoglycemia despite being on basal/bolus therapy., (Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.)