Aim The COVID-19 pandemic caused by infection with the novel coronavirus SARS-CoV-2 is urging the scientific community worldwide to intense efforts for identifying and developing effective drugs and pharmacologic strategies to treat the disease. Many of the drugs that are currently in (pre)clinical development are addressing late symptoms of the disease. This review focuses on potential pharmacologic intervention at an early stage of infection which could result in less-infected individuals and less cases with severe COVID-19 disease due to reduced virus entry into the cells. Method We scanned the literature for evidence on drugs that target the virus entry machinery into host cells and consist mainly of ACE2 and TMPRSS2, as well as other cellular molecules regulating ACE2 expression, such as ADAM-17 and calmodulin. Results Several drugs/drug classes have been identified. Most of them are already used clinically for other indications. They include recombinant soluble ACE2, indirect ACE2 modulators (angiotensin receptor blockers, calmodulin antagonists, selective oestrogen receptor modifiers), TMPRSS2 inhibitors (camostat mesylate, nafamostat mesylate, antiandrogens, inhaled corticosteroids) and ADAM-17 enhancers (5-fluorouracil). Conclusion Several agents have potential for prophylactic and therapeutic intervention at the early stages of SARS-CoV-2 infection and COVID-19 disease and they should be urgently investigated further in appropriate preclinical models and clinical studies.

Hypoglycemia is a common adverse effect of sulfonylurea oral hypoglycemic agents. Impaired metabolism of sulfonylureas due to gene polymorphisms in the metabolic enzyme CYP2C9 might lead to hypoglycemia. In the present study we explored the association of the CYP2C9 variant alleles CYP2C9*2 and CYP2C9*3 with the incidence of hypoglycemic events in diabetic patients receiving the sulfonylureas glimepiride and gliclazide. A total of 92 Type 2 diabetes mellitus (T2DM) patients receiving sulfonylurea and reporting drug-associated hypoglycemia, and 84 T2DM patients receiving sulfonylurea and having never experienced hypoglycemia were included in the study. A sample of 283 nondiabetic controls that had been genotyped earlier served as a second control group. CYP2C9*2 and *3 alleles were detected by use of PCR-RFLP analysis. Frequencies of CYP2C9*1/*3 genotype and CYP2C9*3 allele were significantly lower in T2DM patients than nondiabetic controls (p = 0.003 and p = 0.017, respectively). A total of 11 out of 92 subjects (12%) experiencing hypoglycemia carried the CYP2C9*3 allele, as opposed to only 1 out of 84 subjects (1.2%) free of sulfonylurea-induced hypoglycemia. In a model adjusted for age, BMI, mean daily dose of sulfonylurea, duration of T2DM and renal function, CYP2C9*1/*3 genotype increased the hypoglycemia risk in response to sulfonylurea (odds ratio: 1.687; p = 0.011). However, no differences in CYP2C9*2 allele frequency between the two groups were found. The presence of CYP2C9*3 appears to be protective for development of T2DM. Furthermore, in T2DM patients, CYP2C9*3 increases the risk of hypoglycemia when they are treated with sulfonylureas, possibly due to impaired metabolism of these drugs. CYP2C9 genotyping might thus be a useful tool for predicting adverse effects caused by sulfonylureas and help clinicians in safer prescribing of oral hypoglycemic agents. The potential T2DM protective effect of CYP2C9*3 allele requires further investigation.

Introduction: CYP2C19*17 is a novel variant allele causing ultrarapid metabolism of CYP2C19 substrates. In the present study we investigated the CYP2C19*17 allelic frequency and recalculated previously reported frequencies of the CYP2C19*1/*1 genotype and of all genotype-derived phenotypes for CYP2C19 in the Greek population. Materials & methods: A total of 283 nonrelated healthy Greek ethnic subjects that had already been genotyped for CYP2C19*2 and *3 alleles as well as for CYP2D6 and CYP2C9 variant alleles participated in the study. The CYP2C19*17 allele was genotyped by the PCR-RFLP method. Results: The CYP2C19*17 allele frequency was 19.61%. The prevalence of CYP2C19*17 carriers in the Greek population was estimated at 31.80%, while the frequency of CYP2C19*1/*1 genotype was recalculated to 44.17% from 75.97% in our previous study. Several subjects possessing both CYP2C19*17 and variant alleles of CYP2D6 and CYP2C9 were also identified. Discussion & conclusion: The CYP2C19*17 allele is present in Gre...

Type 2 diabetes mellitus (T2DM) is an increasingly prevalent disease. Several classes of drugs are currently available to treat T2DM patients; however, clinical response to these drugs often exhibi...

Coumarinic oral anticoagulants are life-saving drugs, but are also one of the leading causes of drug-induced major bleeding events. Moreover, there is substantial individual variation in response t...