ABSTRACT
The new coronavirus that emerged, called SARS-CoV-2, is the causative agent of the COVID-19 pandemic. The identification of potential drug candidates that can rapidly enter clinical trials for the prevention and treatment of COVID-19 is an urgent need, despite the recent introduction of several new vaccines for the prevention and protection of this infectious disease, which in many cases becomes severe. Drug repurposing (DR), a process for studying existing pharmaceutical products for new therapeutic indications, represents one of the most effective potential strategies employed to increase the success rate in the development of new drug therapies. We identified raloxifene, a known Selective Estrogen Receptor Modulator (SERM), as a potential pharmacological agent for the treatment of COVID-19 patients. Following a virtual screening campaign on the most relevant viral protein targets, in this work we report the results of the first pharmacological characterization of raloxifene in relevant cellular models of COVID-19 infection. The results obtained on all the most common viral variants originating in Europe, United Kingdom, Brazil, South Africa and India, currently in circulation, are also reported, confirming the efficacy of raloxifene and, consequently, the relevance of the proposed approach. Taken together, all the information gathered supports the clinical development of raloxifene and confirms that the drug can be proposed as a viable new option to fight the pandemic in at least some patient populations. The results obtained so far have paved the way for a first clinical study to test the safety and efficacy of raloxifene, just concluded in patients with mild to moderate COVID-19.
ABSTRACT
Compared to RT-PCR, lower performance of antigen detection assays, including the Lumipulse G SARS-CoV-2 Ag assay, may depend on specific testing scenarios. We tested 594 nasopharyngeal swab samples from individuals with COVID-19 (RT-PCR cycle threshold [Ct] values [≤]40) or non-COVID-19 (Ct values [≤]40) diagnoses. RT-PCR positive samples were assigned to diagnostic, screening, or monitoring groups of testing. With a limit of detection of 1.2 x 104 SARS-CoV-2 RNA copies/ml, Lumipulse showed positive percent agreement (PPA) of 79.9% (155/194) and negative percent agreement of 99.3% (397/400), whereas PPAs were 100% for samples with Ct values of <18 or 18-<25 and 92.5% for samples with Ct values of 25-<30. By three groups, Lumipulse showed PPA of 87.0% (60/69), 81.1% (43/53), or 72.2% (52/72), respectively, whereas PPA was 100% for samples with Ct values of <18 or 18-<25, and was 94.4%, 80.0%, or 100% for samples with Ct values of 25-<30, respectively. RT-PCR positive samples were also tested for SARS-CoV-2 subgenomic RNA and, by three groups, testing showed that PPA was 63.8% (44/69), 62.3% (33/53), or 33.3% (24/72), respectively. PPAs dropped to 55.6%, 20.0%, or 41.7% for samples with Ct values of 25-<30, respectively. All 101 samples with a subgenomic RNA positive result had a Lumipulse assays antigen positive result, whereas only 54 (58.1%) of remaining 93 samples had a Lumipulse assays antigen positive result. In conclusion, Lumipulse assay was highly sensitive in samples with low RT-PCR Ct values, implying repeated testing to reduce consequences of false-negative results.
ABSTRACT
Serological assays for anti-SARS-CoV-2 antibodies are now of critical importance to support diagnosis, guide epidemiological intervention, and understand immune response to natural infection and vaccine administration. We developed and validated new anti-SARS-CoV-2 IgG, IgM and IgA ELISA tests (ENZY-WELL SARS-CoV-2 ELISA, DIESSE Diagnostica Senese S.p.a.) based on whole-virus antigens. We used a total of 553 serum samples including samples from COVID-19 suspected and confirmed cases, healthy donors, and patients positive for other infections or autoimmune conditions. Overall, the assays showed good concordance with the indirect immunofluorescence reference test in terms of sensitivity and specificity. Especially for IgG and IgA, we observed high sensitivity (92.5 and 93.6%, respectively); specificity was high (>96%) for all antibody types ELISAs. In addition, sensitivity was linked to the days from symptoms onset (DSO) due to the seroconversion window, and for ENZY-WELL SARS-CoV-2 IgG and IgA ELISAs resulted 100% in those samples collected after 10 and 12 DSO, respectively. The results showed that ENZY-WELL SARS-CoV-2 ELISAs may represent a valid option for both diagnostic and epidemiological purposes, covering all different antibody types developed in SARS-CoV-2 immune response.
