Potential associations of selected polymorphic genetic variants with COVID-19 disease susceptibility and severity (preprint)

In this study, we analyzed the potential associations of selected laboratory and anamnestic parameters, as well as 12 genetic polymorphisms (SNPs), with clinical COVID-19 occurrence and severity in 869 hospitalized patients. The SNPs analyzed by qPCR were selected based on population-wide genetic (GWAS) data previously indicating association with the severity of COVID-19. We confirmed the associations of disease with several clinical laboratory and anamnestic parameters and found an unexpected association between less severe disease and the loss of smell and taste. In most cases, selected SNP analysis supported earlier results by indicating genetic associations with hospitalization and disease severity, while the potential role of some previously unrecognized polymorphisms has also been observed. A genetic association was indicated between the presence of a reduced-function ABCG2 transporter variant and a less severe disease, which was also observed in diabetic patients. Our current results, which should be reinforced by larger studies, indicate that together with laboratory and anamnestic parameters, genetic polymorphisms may have predictive value for the clinical occurrence and severity of COVID-19.

Interactions of anti-COVID-19 drug candidates with multispecific ABC and OATP drug transporters (preprint)

In the COVID-19 epidemic, several repurposed drugs have been proposed to alleviate the major health effects of the disease. These drugs are often applied together with analgesics or non-steroid anti-inflammatory compounds, and co-morbid patients may also be treated with anticancer, cholesterol-lowering or antidiabetic agents. Since drug ADME-tox properties may be significantly affected by multispecific transporters, here we examined the interactions of the repurposed drugs with the key human multidrug transporters, present in the major tissue barriers and strongly affecting pharmacokinetics. Our in vitro studies, using a variety of model systems, explored the interactions of the antimalarial agents chloroquine and hydroxychloroquine, the antihelmintic ivermectin, and the proposed antiviral compounds, ritonavir, lopinavir, favipiravir and remdesivir with the ABCB1/Pgp, ABCG2/BCRP and ABCC1/MRP1 exporters, as well as the OATP2B1 and OATP1A2 uptake transporters. The results presented here show numerous pharmacologically relevant transporter interactions and may provide a warning for the potential toxicities of these repurposed drugs, especially in drug combinations at the clinic.