Revisiting potential druggable targets against SARS-CoV-2 and repurposing therapeutics under preclinical study and clinical trials: A comprehensive review.

Coronavirus disease-19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is one of the most contagious diseases in human history that has already affected millions of lives worldwide. To date, no vaccines or effective therapeutics have been discovered yet that may successfully treat COVID-19 patients or contain the transmission of the virus. Scientific communities across the globe responded rapidly and have been working relentlessly to develop drugs and vaccines, which may require considerable time. In this uncertainty, repurposing the existing antiviral drugs could be the best strategy to speed up the discovery of effective therapeutics against SARS-CoV-2. Moreover, drug repurposing may leave some vital information on druggable targets that could be capitalized in target-based drug discovery. Information on possible drug targets and the progress on therapeutic and vaccine development also needs to be updated. In this review, we revisited the druggable targets that may hold promise in the development of the anti-SARS-CoV-2 agent. Progresses on the development of potential therapeutics and vaccines that are under the preclinical studies and clinical trials have been highlighted. We anticipate that this review will provide valuable information that would help to accelerate the development of therapeutics and vaccines against SARS-CoV-2 infection.

Prevalence of elevated liver enzymes and its association with type 2 diabetes: A cross-sectional study in Bangladeshi adults.

BACKGROUND: Type 2 diabetes (T2D) is a major public health concern affecting millions of people worldwide. The relationship between liver enzymes and T2D has been reported in limited studies; however, there is still a lack of evidence for the Bangladeshi population. This study aimed to evaluate the prevalence of elevated liver enzymes and examine its association with the prevalence of T2D in Bangladeshi adults. METHODS: A total of 270 individuals (110 diabetic and 160 nondiabetic) were enrolled in the study. Alanine and aspartate aminotransferase (ALT, AST), alkaline phosphatase (ALP) and γ-glutamyltransferase (GGT) activities were measured in blood serum collected from them. T2D was defined as fasting blood glucose (FBG) ≥126 mg/dL or self-reported recent use of insulin or antidiabetic medications. Association between liver enzymes and T2D was evaluated by multinomial logistic regression analysis. RESULTS: Overall, 61.2% of participants in T2D and 37.1% of participants in the nondiabetes group had at least one or more elevated liver enzymes. The mean concentrations of serum ALT, AST, ALP and GGT were significantly higher in the T2D group compared to the nondiabetes group. The prevalence of elevated liver enzymes was significantly higher in the diabetes group compared to the nondiabetes group (P < .01). In regression analysis, serum GGT activity showed an independent association with the prevalence of T2D. CONCLUSIONS: A high prevalence of elevated liver enzymes was observed in subjects having diabetes. Increased serum GGT activity was independently associated with the prevalence of T2D among Bangladeshi adults. More studies of this nature should be carried out in developing countries to get proper insights into the involvement of liver enzymes in T2D.

Association between serum liver enzymes and hypertension: a cross-sectional study in Bangladeshi adults.

BACKGROUND: Hypertension is a major contributing factor to cardiovascular disease and is a leading cause of death in the world. The association between hepatic enzymes and hypertension has been reported in limited studies and the findings are inconsistent; data from Bangladeshi adults are not available yet. This study was conducted to estimate the prevalence of elevated liver enzymes and evaluate the association of elevated liver enzymes with hypertension in Bangladeshi adults. METHODS: In this cross-sectional study, 302 blood samples were collected from adult participants and analyzed the serum concentrations of alanine and aspartate aminotransferase (ALT, AST), alkaline phosphatase (ALP), and γ-glutamyltransferase (GGT) and other markers related to hypertension. Hypertension was defined as resting SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg. Associations between elevated liver enzymes and hypertension were evaluated by multinomial logistic regression. RESULTS: The mean concentrations of serum ALT, AST and GGT were significantly higher in the hypertensive group compared to the normotensive group (p < 0.01, p < 0.01 and p < 0.001, respectively). Overall, 49.2% of subjects in the hypertensive group and 38.1% of individuals in the normotensive group had at least one or more elevated liver enzymes. The prevalence of elevated ALT, AST, and GGT was significantly higher among participants in the hypertensive group compared to the normotensive group (p < 0.01, p < 0.01 and p < 0.001, respectively). An increasing trend for elevated liver enzymes was observed with increasing blood pressure. Serum ALT and GGT showed an independent relationship with hypertension. CONCLUSIONS: The prevalence of elevated liver enzymes was higher in hypertensive individuals. Increased serum ALT and GGT activities were positively associated with hypertension in Bangladeshi adults.

Assessment of the relationship between serum uric acid and glucose levels in healthy, prediabetic and diabetic individuals.

BACKGROUND: In epidemiological studies, serum uric acid (SUA) has been shown to be associated with hypertension and cardiovascular disorders. However, limited studies have evaluated the relationship between SUA and glucose levels in healthy and diabetic individuals and their observed findings are inconsistent. This study aimed to examine the relationship between SUA and fasting blood glucose (FBG) levels among healthy, prediabetic and diabetic individuals in Bangladesh. METHODS: In total, 310 blood samples were collected from 215 male and 95 female subjects and analyzed for FBG, SUA, and lipid levels. All participants were categorized into four quartiles based on SUA concentrations. Diabetes and prediabetes were defined as FBG level ≥ 126 mg/dL and 100-125 mg/dL, respectively. The association between SUA and diabetes was evaluated by multinomial logistic regression analysis. RESULTS: The prediabetic and diabetic individuals had a lower mean level of SUA (338.2 ± 101.6 and 290.9 ± 98.2 µmol/L, respectively) compared to healthy (369.5 ± 110.9 µmol/L) individuals (p < 0.001). SUA was positively associated with BMI, TG and TC but negatively associated with FBG. The prevalence of diabetes was decreased with increasing concentration of SUA across the quartiles. In regression analysis, SUA levels were inversely associated with diabetes mellitus. CONCLUSIONS: SUA levels were high in healthy individuals but declined in prediabetic and diabetic individuals with increasing FBG concentrations. A significant inverse association was observed between the levels of SUA and diabetes in Bangladeshi adults. Further studies are needed to examine the reliability of using SUA to predict diabetes.

Relationship between serum uric acid and hypertension: a cross-sectional study in Bangladeshi adults.

Experimental evidence suggests a causal role of serum uric acid (SUA) in hypertension development. Currently, there are few data available on the association between SUA and hypertension; data from Bangladeshi adults are not available yet. This study evaluated the association of SUA with hypertension among Bangladeshi adults. Blood samples were obtained from 140 males and 115 females and analyzed for SUA and lipid levels. Hypertension was defined as SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg. All participants were divided into four quartiles based on SUA concentrations. Association of SUA with hypertension was evaluated by logistic regression models. The prevalence of hypertension and prehypertension was significantly higher in male (15.4 and 47.6%, respectively) than in the female (5.6 and 33.4%, respectively) subjects (p < 0.01). Males had a higher mean level of SUA (310.7 ± 67.9 µmol/L) than in the females (255.3 ± 69.3 µmol/L) (p < 0.001). Hyperuricemia was prevalent 9.1% in males and 10.3% in females. An increasing trend for hypertension and prehypertension was found in both genders with increasing SUA levels in the quartiles (p < 0.01). SUA levels in the quartiles were positively correlated with blood pressure (p < 0.01). After adjusting for baseline covariates, SUA levels were significantly associated with hypertension (p < 0.01). Findings of this study indicate the significance of maintaining normal SUA level to prevent hypertension.

The relationship between serum uric acid and lipid profile in Bangladeshi adults.

BACKGROUND: Although the link between elevated uric acid and metabolic syndrome has been reported in some studies; the relationship of serum uric acid (SUA) with lipid profile has not well studied or little is known so far. This study was conducted to assess the relationship between SUA and lipid profile among the general adults in Bangladesh. METHODS: In total, 280 blood samples were collected from general adult participants (male, n = 150 and female, n = 130) and analyzed for serum lipid profile (TC, TG, HDL and LDL) and SUA levels. The study subjects were divided by quartiles based on SUA levels (Q1: ≤225 µmol/L, Q2: 226-285 µmol/L, Q3: 286-340 µmol/L and Q4: > 340 µmol/L). Linear regression modeling was used to evaluate the relationship between SUA and lipid levels. RESULTS: The prevalence of hyperuricemia was 9.2% in males and 10.4% in females. The mean level of SUA was significantly higher in male (317 ± 90 µmol/L) than in the female (255 ± 65 µmol/L) subjects (p < 0.001). An increasing trend for elevated lipid profile was observed in both gender with increasing levels of SUA in the quartiles (p < 0.05). In regression analysis, a significant positive correlation was found between SUA and TG, TC and LDL (p < 0.01) while an inverse correlation was observed between SUA and HDL (p < 0.01). After adjusting for potential confounders, lipid profile was linearly associated with SUA levels (p < 0.01 for trend). CONCLUSIONS: Present study showed a significant positive relationship for SUA with TG, TC and LDL levels, and an inverse relationship for SUA with HDL. Early prevention of hyperuricemia and dyslipidemia may be helpful to reduce the incidence of associated cardiovascular diseases.

Prevalence of hyperuricemia and the relationship between serum uric acid and obesity: A study on Bangladeshi adults.

BACKGROUND AND OBJECTIVES: Recent studies have shown that hyperuricemia is commonly associated with dyslipidemia, cardiovascular diseases, hypertension and metabolic syndrome. Elevated serum uric acid has been demonstrated to be associated with obesity in the adult population in many countries; however, there is still a lack of evidence for the Bangladeshi population. The aims of this study were to evaluate the prevalence of hyperuricemia and determine the relationship between serum uric acid (SUA) and obesity among the Bangladeshi adults. METHODS: In this cross-sectional study, blood samples were collected from 260 adults (142 males and 118 females) and analyzed for SUA and lipid profile. All participants were categorized as underweight (n = 11), normal (n = 66), overweight (n = 120) and obese (n = 63) according to the body mass index (BMI) scale for the Asian population. Based on SUA concentration the participants were stratified into four quartiles (Q1: < 232 µmol/L, Q2: 232-291 µmol/L, Q3: 292-345 µmol/L and Q4: > 345 µmol/L). RESULTS: The mean age and BMI of the participants were 32.5 ± 13.3 years and 24.9 ± 3.8 kg/m2, respectively. The average level of SUA was 294 ± 90 µmol/L with a significant difference between males and females (p < 0.001). Overall, the estimated prevalence of hyperuricemia was 9.3% with 8.4% in male and 10.2% in female participants. There were significant increases in the prevalence of obesity (17.4%, 22.2%, 28.6% and 31.8%, respectively, p < 0.01 for trend) across the SUA quartiles. A multiple logistic regression analysis revealed that SUA quartiles were independently associated with the presence of obesity (p < 0.01). CONCLUSION: Present study indicates a significant positive relationship between SUA and obesity among the Bangladeshi adults. Therefore, routine measurement of SUA is recommended in obese individuals to prevent hyperuricemia and its related complications.