ETIDIOH - NEW

  Abstract Molnupiravir is an antiviral medicine that induces lethal copying errors during SARS-CoV-2 RNA replication . Molnupiravir reduced hospitalization in one pivotal trial by 50% and had variable effects on reducing viral RNA levels in three separate trials. We used mathematical models to simulate these trials and closely recapitulated their virologic outcomes . Model simulations suggested lower antiviral potency against pre-Omicron SARS-CoV-2 variants than against Omicron . We estimated that in vitro assays underestimated in vivo potency by 6- to 7-fold against Omicron variants. Our model suggested that because polymerase chain reaction detects molnupiravir mutated variants, the true reduction in non-mutated viral RNA was underestimated by approximately 0.4 log10 in the two trials conducted while Omicron variants dominated. Viral area under the curve estimates differed significantly between non-mutated and mutated viral RNA. Our results reinforce past work suggesting that in...

  ABSTRACT Bourbon virus (BRBV) is an emerging tick-borne virus that can cause severe and fatal disease in humans . BRBV is vectored via the Amblyomma americanum tick , which is widely distributed throughout the central, eastern, and southern United States . Serosurveillance studies in Missouri and North Carolina identified BRBV-neutralizing antibodies in approximately 0.6% of tested individuals . To date, no specific antiviral therapy exists. As part of an initial screen, several nucleoside analogs were tested for their ability to inhibit BRBV replication in cell culture. Among the compounds assessed, molnupiravir , an antiviral drug with oral availability and broad spectrum antiviral activity against RNA viruses, showed antiviral activity against BRBV production in vitro. In vivo, pre-exposure administration of molnupiravir protected susceptible type I interferon receptor knockout (Ifnar1-/-) mice against lethal BRBV infection. The protection by molnupiravir was associated with l...

  Abstract Objectives There have been few studies in pregnant women of medications that are used to reduce severe complications from COVID-19 infection. Currently, nirmatrelvir/ritonavir (Paxlovid) is recommended by the National Institutes for Health to treat non-hospitalized pregnant patients with mild-to-moderate COVID-19 illness. The aim of this study was to determine the transplacental passage of molnupiravir, nirmatrelvir/ritonavir and favipiravir utilizing an ex vivo placental perfusion model. Methods Human placental cotyledons were continuously perfused in a double open circuit. The study molecules and antipyrine, a marker of placental viability, were dissolved in the maternal solution. The experiment was conducted over 90 minutes, and every 5 minutes, samples of the maternal solution and fetal exchange solutions were collected for analysis. We calculated the concentrations of study molecules, fetal transfer ratios and the clearance indexes to determine placental transfer. R...

Highlights •  Mol shows greater antiviral effects against IAV and IBV in cell cultures. •  Mol and Ose together showed a synergistic effect against IAV. •  In mice, Mol alone or with Ose reduced lung injury and viral load. Abstract Oseltamivir, a neuraminidase inhibitor, is widely used in the clinic for treating influenza virus infections . However, suboptimal efficacy and risk of drug resistance development remain major challenges. Molnupiravir , a ribonucleoside analog, was originally developed to treat influenza, but was repurposed and first approved for treating COVID-19 in 2021. Considering their complementary mode-of-actions, this study aimed to investigate the combinatorial activities of oseltamivir and molnupiravir against influenza virus infections . In cell culture models, we found that β-d-N4-hydroxycytidine (NHC), the active form of molnupiravir, exerted more potent antiviral activities against influenza A and B viruses , when compared to oseltamivir treatment...

Abstract Recent investigations have demonstrated a relationship between the persistence of SARS-CoV-2 and post-COVID-19 conditions . Building upon a potential connection between SARS-CoV-2 persistence and early virologic rebound, we examine the association of early virologic rebound with post-acute mortality and hospitalization due to post-acute sequelae among hospitalized patients with COVID-19 in Hong Kong . Our study includes 13,859, 3959, and 4502 patients in the all-patient, nirmatrelvir/ritonavir, and molnupiravir group , respectively. Results show that patients who experienced virologic rebound exhibited a significantly higher risk of post-acute mortality (hazard ratio [HR], 1.52; 95% confidence interval [CI], 1.36–1.70) with a risk difference [RD] of 7.19%, compared with patients without virologic rebound. A similar increase in the risk of post-acute mortality is also observed in nirmatrelvir/ritonavir-treated patients (HR, 1.78; 95% CI, 1.41–2.25; RD, 12.55%) and molnupiravir-...

Summary Background Molnupiravir and nirmatrelvir–ritonavir are oral antivirals that have shown efficacy in preventing disease progression in outpatients with COVID-19. We aimed to evaluate these treatments for patients hospitalised with COVID-19 pneumonia, for whom data on these antivirals are scarce. Methods The RECOVERY trial is a randomised, controlled, open-label, adaptive platform trial testing treatments for COVID-19 . In this study we report the molnupiravir and nirmatrelvir–ritonavir comparisons from the RECOVERY trial. In each comparison, participants aged 18 years and older were randomly allocated (1:1) to the relevant antiviral (5 days of molnupiravir 800 mg twice daily or 300 mg nirmatrelvir and 100 mg ritonavir twice daily) in addition to usual care, or to usual care alone. The molnupiravir comparison was conducted at 75 hospitals in the UK, two in Nepal, and two in Indonesia ; the nirmatrelvir–ritonavir comparison was conducted at 32 hospitals in the UK. Participants coul...