The current coronavirus (COVID-19) pandemic is exacerbated by the absence of effective therapeutic agents. Notably, patients with COVID-19 and comorbidities such as hypertension and cardiac diseases have a higher mortality rate. An efficient strategy in response to this issue is repurposing drugs with antiviral activity for therapeutic effect. Digoxin (DIG) and ouabain (OUA) are FDA drugs for heart diseases that have antiviral activity against several coronaviruses. Thus, we aimed to assess antiviral activity of DIG and OUA against SARS-CoV-2 infection. The half-maximal inhibitory concentrations (IC50) of DIG and OUA were determined at a nanomolar concentration. Progeny virus titers of single-dose treatment of DIG, OUA and remdesivir were approximately 103-, 104- and 103-fold lower (> 99% inhibition), respectively, than that of non-treated control or chloroquine at 48 h post-infection (hpi). Furthermore, therapeutic treatment with DIG and OUA inhibited over 99% of SARS-CoV-2 replication, leading to viral inhibition at the post entry stage of the viral life cycle. Collectively, these results suggest that DIG and OUA may be an alternative treatment for COVID-19, with potential additional therapeutic effects for patients with cardiovascular disease.
Background As the coronavirus disease 2019 (COVID-19) pandemic continues, there are concerns regarding waning immunity and the emergence of viral variants. The immunogenicity of Ad26.COV2.S against wild-type (WT) and variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) needs to be evaluated. Method This prospective cohort study was conducted between June 2021 and January 2022 at two university hospitals in South Korea. Healthy adults who were scheduled to be vaccinated with Ad26.COV2.S were enrolled in this study. The main outcomes included anti-spike (S) IgG antibody and neutralizing antibody responses, S-specific T-cell responses (interferon-γ enzyme-linked immunospot assay), solicited adverse events (AEs), and serious AEs. Results Fifty participants aged ≥ 19 years were included in the study. Geometric mean titers (GMTs) of anti-S IgG were 0.4 U/mL at baseline, 5.2 ± 3.0 U/mL at 3–4 weeks, 55.7 ± 2.4 U/mL at 5–8 weeks, and 81.3 ± 2.5 U/mL at 10–12 weeks after vaccination. GMTs of 50% neutralizing dilution (ND50) against WT SARS-CoV-2 were 164.6 ± 4.6 at 3-4 weeks, 313.9 ± 3.6 at 5–8 weeks, and 124.4 ± 2.6 at 10–12 weeks after vaccination. As for the S-specific T-cell responses, the median number of spot-forming units/10 6 peripheral blood mononuclear cell was 25.0 (5.0–29.2) at baseline, 60.0 (23.3–178.3) at 5-8 weeks, and 35.0 (13.3–71.7) at 10–12 weeks after vaccination. Compared to WT SARS-CoV-2, ND50 against Delta and Omicron variants was attenuated by 3.6-fold and 8.2-fold, respectively. The most frequent AE was injection site pain (82%), followed by myalgia (80%), fatigue (70%), and fever (50%). Most AEs were grade 1–2, and resolved within two days. Conclusion Single-dose Ad26.COV2.S was safe and immunogenic. NAb titer and S-specific T-cell immunity peak at 5–8 weeks and rather decrease at 10–12 weeks after vaccination. Cross-reactive neutralizing activity against the Omicron variant was negligible.
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