Lagevrio (molnupiravir) / Emory University, Ridgeback Biotherap, Merck (MSD), Cipla - LARVOL DELTA

How Can Pharmacology Help Us Overcome the Challenges of Drug Repositioning as Antivirals to Treat Emerging Pathogens? The Example of Covid-19. (PubMed, Clin Transl Sci) - "This narrative review critically examines the pharmacological and methodological factors that contributed to these unsuccessful outcomes, paying particular attention to tests of azithromycin and hydroxychloroquine. The relative success of antivirals including molnupiravir, nirmatrelvir, and remdesivir, which were either novel or previously unapproved compounds, suggests the value of designing and developing targeted antivirals. We must coordinate global research, develop pharmacologically sound strategies, and use evidence-based decision-making to effectively prepare for future pandemics and quickly produce effective treatments."

Journal • Review • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Outpatient Treatment of Confirmed COVID-19: A Living, Rapid Review for the American College of Physicians (Version 3). (PubMed, Ann Intern Med) - "125 mg of ensitrelvir may not reduce time to recovery and may result in no difference in serious adverse events (both low CoE) but may increase adverse events (44.2% vs. 24.8%; low CoE)...Simnotrelvir-ritonavir reduces time to recovery (-35.8 median hours; high CoE) and probably increases adverse events (28.9% vs. 21.6%; moderate CoE). There was no difference in recovery between molnupiravir and favipiravir (high CoE) and nirmatrelvir-ritonavir and molnupiravir (low CoE)...American College of Physicians. (PROSPERO: CRD420251029146; OSF: https://osf.io/ywp6u)."

Journal • Review • Infectious Disease • Novel Coronavirus Disease

Outpatient Treatment of Confirmed COVID-19 in Symptomatic Adults: Living, Rapid Practice Points From the American College of Physicians (Version 3). (PubMed, Ann Intern Med) - "Consider nirmatrelvir-ritonavir combination therapy to treat symptomatic patients with confirmed mild to moderate COVID-19 in the outpatient setting who are within 5 days of the onset of symptoms and at a high risk for progressing to severe disease. Consider molnupiravir to treat symptomatic patients with confirmed mild to moderate COVID-19 in the outpatient setting who are within 5 days of the onset of symptoms and at a high risk for progressing to severe disease...Do not use sotrovimab to treat patients with confirmed mild to moderate COVID-19 in the outpatient setting. The PHMSC is retiring this topic from living status considering that this update and previous surveillance have not yielded important changes to the practice points."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Treatment Duration of Each Anti-COVID-19 Agent Used in a Tertiary Hospital in Japan. (PubMed, Cureus) - "Four anti-COVID-19 agents, nirmatrelvir/ritonavir (Nir/r), ensitrelvir (ESV), molnupiravir (MPV), and remdesivir (RDV), have been used in Japan for adult patients, and their clinical effectiveness, especially treatment duration and reduction of viral antigen titers, was investigated. However, the treatment durations differed significantly: 4.09 days with Nir/r, 4.76 days with ESV, 4.74 days with MPV, and 5.08 days with RDV. These data suggest that the anti-viral activity of each anti-COVID-19 agent may differ in clinical use."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Value of Emerging and Existing Pre-prophylaxis and Therapeutic Options for COVID-19 in Transplant Recipients: A Systematic Review of Economic Evaluations. (PubMed, Pharmacoecon Open) - "Cost effectiveness varied widely across studies due to differences in variant periods, population risk profiles, model assumptions, and healthcare systems. Future research should integrate variant-specific effectiveness, real-world vaccine responsiveness, long-term COVID-19 outcomes, and adverse events to better inform resource allocation for transplant and other high-risk populations."

HEOR • Journal • Review • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • Transplantation

Patterns of use of oral antivirals for COVID-19 in people 70 years and over in Victoria, Australia: a linked data study. (PubMed, BMC Infect Dis) - No abstract available

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Developing Synthetic Full-Length SARS-CoV-2 cDNAs and Reporter Viruses for High-Throughput Antiviral Drug Screening. (PubMed, Viruses) - "Antiviral assays measuring replication inhibition by Remdesivir, Molnupiravir, and Nirmatrelvir, based on Nluc expression, yielded IC50 values and selectivity indices consistent with published ranges. Finally, Delta Nluc viruses replicated in primary human bronchial epithelial cells, demonstrating the application of clone-derived viruses in physiologically relevant models. The SARS-CoV-2 cDNA clones and Nluc reporter viruses derived from DNA synthesis services provide a rapid, scalable reverse genetics platform for generating new viruses and developing assays to rapidly assess antiviral compounds against current and emerging SARS-CoV-2 variants or coronaviruses that may emerge in the future."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

The Therapeutic Potential for Steroid Treatment Strategies in the Treatment of Murine Venezuelan Equine Encephalitis Virus (VEEV) Infection. (PubMed, Viruses) - "When combined with the antiviral drug molnupiravir, the negative effects of the dexamethasone treatment (20 and 50 mg/kg) were absent, and the positive disease severity-reducing effects remained. When combined with a specific VEEV monoclonal antibody (1A3B7), dexamethasone significantly reduced the antibody's protective effects. These data present currently unique insights into how anti-inflammatory approaches might benefit patients with VEEV disease and where caution might be advised."

Journal • Preclinical • CNS Disorders • Immune Modulation • Immunology • Infectious Disease • Inflammation

Safety and Efficacy of Concomitant Nirmatrelvir/Ritonavir and Direct Oral Anticoagulant Therapies for COVID-19 Among Patients With Atrial Fibrillation. (PubMed, J Am Heart Assoc) - "In a territory-wide cohort of hospitalized patients with COVID-19 and atrial fibrillation on a DOAC, nirmatrelvir/ritonavir therapy was associated with lower unadjusted 30-day all-cause death compared with RNA-dependent RNA polymerase inhibitors; however, this difference was not significant after adjusting for age and COVID-19 severity."

Journal • Atrial Fibrillation • Cardiovascular • Infectious Disease • Ischemic stroke • Myocardial Infarction • Novel Coronavirus Disease

Evaluation of the cardiopulmonary effects of repurposed COVID-19 therapeutics in healthy rats. (PubMed, Sci Rep) - "Hydroxychloroquine (HCLQ), favipiravir (FAVI), molnupiravir (MOL) and dexamethasone (DEX) are recently used drugs, some of which are currently used in the treatment of Coronavirus Disease (COVID-19). Drugs used alone or in combination in the treatment of COVID-19 show immunoreactions using different pathways related to apoptosis and necroptosis. Further studies are needed to elucidate the effects of these drugs."

Journal • Preclinical • Cardiovascular • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CASP3 • VIM

AGILE (Early Phase Platform Trial for COVID-19) (clinicaltrials.gov) - P1/2 | N=600 | Recruiting | Sponsor: University of Liverpool | Trial completion date: Oct 2026 ➔ Jul 2026 | Trial primary completion date: Oct 2026 ➔ Jul 2026

Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

SARS-CoV-2 infectious shedding and rebound among adults with and without oral antiviral use: two case-ascertained prospective household studies. (PubMed, Lancet Microbe) - "COVID-19 oral antiviral treatment was associated with earlier cessation of infectious viral shedding in the absence of viral RNA rebound. However, treatment with antivirals was also associated with a brief rebound in SARS-CoV-2. Communication of these transmission risks and benefits could help eligible patients at high risk of severe COVID-19 and clinicians make informed decisions surrounding oral antiviral use."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Molnupiravir: A Prodrug of the Ribonucleoside β-D-N4-Hydroxycytidine Triphosphate Inhibits the Propagation of Nervous Necrosis Virus in Grouper Brain Cells. (PubMed, J Fish Dis) - "Finally, the molecular docking simulation model supports the interaction between NHC-TP and GGNNV RdRp for the successful therapeutics. These results demonstrated that Molnupiravir is a very effective therapeutic drug for controlling viral nervous necrosis caused by NNV infection."

Journal • CNS Disorders • Infectious Disease • Retinal Disorders

Persistent SARS-CoV-2 Infection in an Immunocompromised Host Treated Successfully With the Japanese Herbal Medicine, Mao-to: A Case Report. (PubMed, Am J Case Rep) - "Clinically, cases that do not respond to guideline-based antivirals, such as molnupiravir, remdesivir, and nirmatrelvir/ritonavir, are occasionally encountered, but effective therapeutic alternatives remain scarce. In addition, 14 days of Mao-to treatment cost approximately 1200 JPY (USD $8), significantly less than extended courses of standard antivirals. This case suggests the potential utility of traditional herbal medicine in managing persistent SARS-CoV-2 infections when conventional therapies fail."

Journal • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Novel Coronavirus Disease • Oncology • Respiratory Diseases

Viral kinetics in adults with Covid-19 treated with nirmatrelvir-ritonavir or molnupiravir: a population-based, observational cohort study. (PubMed, Virol J) - "These findings provide population-level evidence on post-treatment viral kinetics of oral antivirals during the Omicron wave."

Journal • Observational data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Using error-corrected sequencing for evaluating mutagenicity of molnupiravir in humans. (PubMed, Mutagenesis) - "Also, the spectra of mutations in the MOV group did not show any evidence of the mutational signature expected from exposures to MOV or NHC based on data from mammalian cell culture models. Within the limits of this study, the dose of MOV authorized for the treatment of COVID-19 under emergency use authorization appears to have no mutational consequences for treated patients."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Inhibitory effects of molnupiravir on Crimean-Congo hemorrhagic fever virus polymerase. (PubMed, NAR Mol Med) - "Next-generation sequencing revealed that NHC induced predominantly G-to-A and C-to-U transitions in CCHFV. Collectively, these results provide mechanistic evidence to consider the development of mutagenic nucleotides as possible treatments for CCHFV infection."

Journal • Hematological Disorders • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Combination antiviral and anti-inflammatory therapy mitigates persistent neurological deficits in mice post SARS-CoV-2 infection. (PubMed, Proc Natl Acad Sci U S A) - "Treatment with antivirals (nirmatrelvir and molnupiravir) at the time of infection minimally prevented neurological abnormalities, consistent with patient data. Together these results demonstrate that neurological dysfunction in SARS-CoV-2 infected mice resembles human neurodegenerative disease and indicate that minimizing inflammation early after SARS-CoV-2 infection may be critical for decreasing neurological PASC. The requirement for decreasing inflammation soon after infection may also explain why antiviral therapy has had inconsistent effects in patients."

Journal • Preclinical • CNS Disorders • Cognitive Disorders • Infectious Disease • Inflammation • Novel Coronavirus Disease • Otorhinolaryngology • Respiratory Diseases

Repurposing of FDA-Approved Antiviral Drugs Against Monkeypox Virus: Comparative In Vitro Screening and Structure Based In Silico Studies. (PubMed, Pharmaceuticals (Basel)) - "Twenty-three FDA-approved drugs, including Abacavir, Acyclovir, Amantadine, Chloroquine, Daclatasvir, Dolutegravir, Entecavir, Favipiravir, Hydroxychloroquine, Lamivudine, Molnupiravir, Nevirapine, Oseltamivir, Penciclovir, Remdesivir, Ribavirin, Sofosbuvir, Tenofovir, Valaciclovir, Valganciclovir, Velpatasvir, Zanamivir, and Zidovudine, were screened for potential anti-monkeypox activity in vitro...The employed computational methods indicate that remdesivir demonstrated superior binding patterns with elevated scores and stable complexes throughout the simulation. Our findings showed that Remdesivir therapeutic compound is potent against the tested strain of MPXV, and exhibited a robust binding affinity for Thymidylate Kinase, A42R Profilin-Like Protein, and VACV D13 enzymes, and thus may potentially be utilized as antiviral for the treatment of monkeypox virus."

FDA event • Journal • Preclinical • Infectious Disease

Medication errors and associated serious outcomes in COVID-19 antivirals: a real-world study based on FDA Adverse Event Reporting System database. (PubMed, Ther Adv Drug Saf) - "The Food and Drug Administration (FDA) authorized three COVID-19 antivirals, including remdesivir, nirmatrelvir/ritonavir, and molnupiravir. Medication errors involving COVID-19 antivirals remain a safety concern, particularly with molnupiravir. Errors were associated with serious outcomes, highlighting the need for targeted safety interventions in prescribing and dispensing practices to reduce preventable harm."

Adverse events • Journal • Real-world evidence • Infectious Disease • Novel Coronavirus Disease

Designing Novel Compound Candidates Against SARS-CoV-2 Using Generative Deep Neural Networks and Cheminformatics. (PubMed, Int J Mol Sci) - "In this study, the small molecule structure of Molnupiravir which has been authorized by the U.S. FDA for emergency use was used to be a model in a similarity search based on the BIOVIA Available Chemicals Directory (BIOVIA ACD) database using the BIOVIA Discovery Studio (DS) software (version 2022)...We provide a combination of generative deep neural networks and cheminformatics for developing new anti-SARS-CoV-2 compounds. However, additional chemical refinement and experimental validation will be required to determine its stability, mechanism of action, and antiviral efficacy."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Design, synthesis, and antiviral activity evaluation of the bis-ester prodrug of N4-hydroxycytidine phosphate. (PubMed, Bioorg Med Chem Lett) - "Compounds 2328 and 2322 showed better antiviral activity than molnupiravir. The EC50s of 2328 against VSV, HMPV-A2, and RSV-A2 viruses were 2.19 μM, 35.6 μM, and 53.5 μM, respectively, and the EC50s of 2322 against VSV, HMPV-A2, and RSV-A2 were 6.23 μM, 52.8 μM, and 28.2 μM, respectively. Structure-activity relationships indicate that the antiviral activity of compounds at the cellular level is closely linked to the structure of the prodrug's phosphate ester, whereas the ester group on the N4-hydroxyl is more tolerant of diverse functional groups."

Journal

Persistent COVID-19 in Patients With Hematological Malignancies: A Focused Review in the Omicron Era. (PubMed, Clin Lymphoma Myeloma Leuk) - "We carried out a comprehensive literature review of Omicron pCOVID-19 occurring in HM patients, compiled the scattered evidence, and provide practical recommendations which can be of guide to clinicians. Main topics discussed within this review include efficacy of vaccinations in HM patients, risk factors for developing pCOVID-19 (B-cell depleting agents, bendamustine + rituximab therapy, bispecific T-cell engagers, etc.), treatment of pCOVID-19 including extended/sequential/combination therapy incorporating antivirals (nirmatrelvir/ritonavir, remdesivir, molnupiravir, and ensitrelvir) and convalescent plasma/intravenous immunoglobulin therapy, monitoring pCOVID-19 with reverse transcription (RT)-PCR, and optimal target cycle threshold values as goals of therapy."

Clinical • Journal • Review • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Novel Coronavirus Disease • Oncology • Respiratory Diseases

Effectiveness of nirmatrelvir/ritonavir and molnupiravir in reducing the risk of short-term and long-term cardiovascular complications of COVID-19: a target trial emulation study. (PubMed, Nat Commun) - "This study demonstrated the effectiveness of nirmatrelvir/ritonavir in reducing the risks of short- and long-term cardiovascular complications following a SARS-CoV-2 infection among the hospitalized population. Our findings suggested health-related benefits of prescribing nirmatrelvir/ritonavir over molnupiravir against severe cardiovascular post-acute sequelae of COVID-19 in the long term."

Journal • Cardiovascular • CNS Disorders • Coronary Artery Disease • Heart Failure • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • Vascular Neurology

TURN-COVID Biobank: The Dutch Cohort Study for the Evaluation of the Use of Neutralizing Monoclonal Antibodies and Other Antiviral Agents Against SARS-CoV-2 (clinicaltrials.gov) - P=N/A | N=1178 | Completed | Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) | Recruiting ➔ Completed | Trial completion date: Jun 2024 ➔ Sep 2025 | Trial primary completion date: Jun 2024 ➔ Sep 2025

Trial completion • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases