Flumadine (rimantadine) / AbbVie - LARVOL DELTA

Activity and cellular distribution of ORF3a mutants of SARS-CoV-2 variants of concern. (PubMed, J Gen Virol) - "Intracellular distribution was similar for all variants. The VOC mutants ORF3a-S171L and ORF3a-Q57H showed reduced cytotoxic activity and sensitivity to the viroporin inhibitor rimantadine, respectively, suggesting these positions to be relevant for ORF3a function and a starting point for the search of novel antiviral drugs."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Repurposing of Some Nucleoside Analogs Targeting Some Key Proteins of the Avian H5N1 Clade 2.3.4.4b to Combat the Circulating HPAI in Birds: An In Silico Approach. (PubMed, Viruses) - "(3) Molecular docking revealed strong binding affinities for both sofosbuvir and GS441524, particularly with the NA and PB2/CBD protein targets...The MM-GBSA binding free energy calculations further supported these findings, as GS441524 displayed more favorable binding energies compared to several known standard inhibitors, including F0045S for HA, Zanamivir for NA, Rimantadine and Amantadine for M2, and PB2-39 for PB2/CBD...These results further support the potential repurposing of GS441524 as a promising therapeutic candidate against H5N1 avian influenza clade 2.3.4.4b. However, further functional studies are required to validate these in silico predictions and support the inhibitory action of GS441524 against the targeted proteins of H5N1, specifically clade 2.3.4.4b."

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

Aryl benzoyl hydrazide derivatives as potent inhibitors of the NS2B-NS3 protease and RNA-dependent RNA polymerase of the zika virus. (PubMed, In Silico Pharmacol) - "To identify molecules that can strongly bind to the substrate binding site of the NS2B-NS3 protease of the ZIKV, interactions of several aryl benzoyl hydrazide (ABH) derivatives (10b, 10c, 10g, 11p, and 11q) and some anti-influenza drugs (Zanamivir, Laninamivir, Baloxavir, Oseltamivir, Rimantadine, Peramivir, and Amantadine) with the ZIKV NS2B-NS3 protease are studied herein by using combined density functional theoretic, docking, molecular dynamics (100 ns MD simulations), and free-energy methods...Computed ADMET parameters, Lipinski's rule of five, and binding affinities suggest that 11q would be a better drug candidate against ZIKV infections. The online version contains supplementary material available at 10.1007/s40203-025-00395-5."

Journal • Infectious Disease • Influenza • Respiratory Diseases

In silico determination of novel SARS-CoV-2 envelope protein ion channel inhibitors. (PubMed, Comput Struct Biotechnol J) - "All ligands were compared with the known inhibitor rimantadine and showed stronger binding to the protein. These in silico results highlight the potential of focusing on the 2-EPRO ion channel in the development of novel COVID-19 therapeutics and pave the way for further in vitro and in vivo studies."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Search for Antiviral Preparations in Series of New Derivatives of N-Substituted Piperidines. (PubMed, Molecules) - "The cytotoxicity of the studied substances in vitro was assessed using the MTT test. Based on the results of the antiviral activity against the influenza A virus, it can be concluded that all substances are effective against the influenza A/H1N1 virus compared to the commercial preparations Tamiflu and Rimantadine."

Journal • Infectious Disease • Influenza • Respiratory Diseases

FIFTY-YEAR ANALYSIS OF INFLUENZA VACCINE EFFECTIVENESS AND ANTIVIRAL USE PATTERNS THROUGH MACHINE LEARNING: IMPLICATIONS FOR PAEDIATRIC INFLUENZA MANAGEMENT (ESPID 2025) - "Data were stratified by virus subtypes, including Influenza A(H1N1), A(H3N2), and Influenza B, as well as by the use of major antivirals such as Amantadine, Rimantadine, Zanamivir, Oseltamivir, Peramivir, and Baloxavir...Conclusions/Learning Points This analysis highlights the dynamic nature of influenza vaccine effectiveness and antiviral medication consumption over five decades. The findings underscore the necessity of ongoing research, global surveillance, and adaptability in influenza prevention and treatment strategies to address changing epidemiological patterns, particularly in vulnerable populations such as children."

Machine learning • Infectious Disease • Influenza

Novel derivatives of thiohydantoin-containing tetrahydro-β-carboline possess activity against influenza virus at late stages of viral cycle without affecting viral neuraminidase. (PubMed, Arch Pharm (Weinheim)) - "Of the 23 compounds under investigation, 10 (43.5%) displayed a selectivity index (SI) of 10 or higher, their activity strongly exceeding that of the reference compound rimantadine...However, no direct inhibiting activity against viral neuraminidase has been demonstrated. The results obtained can be considered as a rationale for further structural optimization and study of this group as potential broad-range antivirals effective against influenza viruses."

Journal • Infectious Disease • Influenza • Respiratory Diseases

Molecular biophysics and inhibition mechanism of influenza virus A M2 viroporin by adamantane-based drugs - Challenges in designing antiviral agents. (PubMed, J Struct Biol X) - "Amantadine is a prototype AM2 channel blocker and inhibitor of influenza A AM2 wild type (serine-31) replication...Previous debates on the mechanism of drug binding and inhibition were due to the different membrane mimetic environment, the excess of the drug, and the method used, rather than the accuracy of the experiments. The collective knowledge acquired can inspire research for the development of new antivirals against influenza viruses and provide experience on the application of molecular biophysics to other viroporins."

Journal • Infectious Disease • Influenza • Respiratory Diseases

Conformation and Membrane Topology of the N-Terminal Ectodomain of Influenza A M2 Protein. (PubMed, Membranes (Basel)) - "Results are consistent with a turn in the middle of the ectodomain that changes in proximity to the membrane surface upon the addition of cholesterol or the antiviral drug rimantadine. Similarly to other domains of M2 protein, lineshape analysis suggests that the N-terminal ectodomain can adopt multiple conformations."

Journal • Infectious Disease • Influenza • Respiratory Diseases

Antiviral Mechanisms and Preclinical Evaluation of Amantadine Analogs that Continue to Inhibit Influenza A Viruses with M2S31N-Based Drug Resistance. (PubMed, Antiviral Res) - "To better manage seasonal and pandemic influenza infections, new drugs are needed with enhanced activity against amantadine- and rimantadine-resistant influenza A virus (IAV) strains containing the S31N variant of the viral M2 ion channel (M2S31N). Finally, a pilot toxicity study in mice demonstrated that 38 and 49 were tolerated at 30 mg/kg. Together, these results indicate that amantadine analogs act on multiple, complementary mechanisms to inhibit replication of M2S31N viruses."

Journal • Preclinical • Infectious Disease • Influenza • Respiratory Diseases

Revealing the mechanism of two rimantadine derivatives inhibiting Aβ aggregation and destabilizing Aβ protofibrils by molecular dynamics simulation. (PubMed, Colloids Surf B Biointerfaces) - "Para exhibits a higher binding affinity and is more effective in inhibiting Aβ aggregation and destabilizing protofibrils. These findings provide valuable insights into the atomic-level mechanisms by which meta and para inhibit Aβ aggregation, offering promising avenues for the exploration of potential therapeutics for Alzheimer's disease (AD)."

Journal • Alzheimer's Disease • CNS Disorders • Immunology

Study on the concentration of acetylated rimantadine metabolites in the diagnosis of early breast cancer (ChiCTR) - P=N/A | N=0 | Recruiting | Sponsor: The First Hospital Affiliated Hospital of Nanjing Medical University; The First Hospital Affiliated Hospital of Nanjing Medical University

New trial • Breast Cancer • Oncology • Solid Tumor

Antiviral Activity of (1S,9aR)-1-[(1,2,3-Triazol-1-yl)methyl]octahydro-1H-quinolizines from the Alkaloid Lupinine. (PubMed, Molecules) - "The obtained biological data are in agreement with the results of molecular docking, which showed strong binding energies of the investigated compounds under study with biological targets-hemagglutinin and neuraminidase proteins. Following the evaluation of antiviral efficacy among the studied triazolyl derivatives of lupinine, four compounds have been identified for subsequent comprehensive in vitro and in vivo investigations to further elucidate their antiviral properties."

Journal • Infectious Disease • Influenza • Respiratory Diseases

Antivirals for post-exposure prophylaxis of influenza: a systematic review and network meta-analysis. (PubMed, Lancet) - "Post-exposure prophylaxis with zanamivir, oseltamivir, laninamivir, or baloxavir probably decreases the risk of symptomatic seasonal influenza in individuals at high risk for severe disease after exposure to seasonal influenza viruses. Post-exposure prophylaxis with zanamivir, oseltamivir, laninamivir, or baloxavir might reduce the risk of symptomatic zoonotic influenza after exposure to novel influenza A viruses associated with severe disease in infected humans."

Clinical • Journal • Retrospective data • Review • Infectious Disease • Influenza • Respiratory Diseases

Inhibitors of the small membrane (M) protein viroporin prevent Zika virus infection. (PubMed, Elife) - "Finally, rimantadine effectively blocked ZIKV viraemia in preclinical models, supporting that M constitutes a physiologically relevant target. This could be explored by repurposing rimantadine, or development of new M-targeted-therapies."

Journal • Infectious Disease

Synthetic and biological assessment of adamantane-ferrocene hybrids (ACS-Fall 2024) - "On the other hand, adamantane is a unique tricyclic compound, known for its structural rigidity, lipophilicity, and effective pharmacological activity resulting in antiviral drugs like Rimantadine and Amantadine. Meanwhile, antioxidant activity assays have been conducted. Further comparisons, as well as synthetic and biological evaluations, will be addressed for the obtained derivatives."

Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Flow analysis-solid phase extraction system and UHPLC-MS/MS analytical methodology for the determination of antiviral drugs in surface water. (PubMed, Environ Sci Pollut Res Int) - "An automated flow analysis-solid phase extraction (FA-SPE) system and methodology of ultra-high-performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) analysis were developed for the determination of selected antiviral drugs (acyclovir, amantadine, rimantadine, and oseltamivir) in water samples. The proposed method was successfully applied to analyse tap, drinking, and river water samples, revealing the presence of amantadine at a concentration of 40.1 pg mL-1 in one sample. The environmental impact of the developed FA-SPE sample preparation procedure was also assessed using the AGREEprep metric tool and compared with five other literature methods, achieving the most sustainable outcome."

Journal

Development and validation of Mayaro virus with luciferase reporter genes as a tool for antiviral assays. (PubMed, Heliyon) - "Employing the infectious clone, we described the effect of Rimantadine, an FDA-approved Alzheimer's drug, as a repurposing agent for MAYV but with a broad-spectrum activity against Zika virus infection. Additionally, we validated MAYV-nanoluc as a tool for antiviral drug screening using the compound EIDD-2749 (4'-Fluorouridine), which acts as an inhibitor of alphavirus RNA-dependent RNA polymerase."

Journal • Alzheimer's Disease • CNS Disorders • Infectious Disease

Adamantane ferrocenyl derivatives as potential antiviral agents | Poster Board #1925 (ACS-Sp 2024) - "Hence, the inclusion of the ten-carbon tricyclo, Adamantane, used in antiviral drugs including Rimantadine and Amantadine, leads to hypothesize that a synergistic effect will be prevalent after the addition of the compounds into the unique chalcone structure. Characterization via IR, 1 H-NMR and 13 C-NMR spectroscopy and XRD crystallography was performed. The scaffold modifications will be compared and evaluated for biological activity."

Infectious Disease • Malaria • Novel Coronavirus Disease • Oncology • Respiratory Diseases

Tackling Influenza A virus by M2 ion channel blockers: Latest progress and limitations. (PubMed, Eur J Med Chem) - "Rimantadine and amantadine are two well-known drugs that act on the M2 protein. It also discusses the M2 structure and its role, and the change in the structure leads to mutant variants of influenza A virus. We also shed light on the recently identified compounds acting against wild-type and mutated M2 proteins of influenza virus A. These scaffolds could be an alternative to M2 inhibitors and be developed as antibiotics for treating influenza infections."

Journal • Review • Infectious Disease • Influenza • Respiratory Diseases

Highly Sensitive Magnetic-Nanoparticle-Based Immunochromatography Assay for Rapid Detection of Amantadine in Chicken and Eggs. (PubMed, Biosensors (Basel)) - "There was no cross-reaction with rimantadine and ribavirin. The vLOD in real samples was 1.0 µg/kg. The developed MICA has the advantages of convenience, speed, and sensitivity, which make it suitable for the on-site rapid detection of AMD residues in chicken tissues and eggs."

Journal

Immune escape of head and neck cancer mediated by the impaired MHC-I antigen presentation pathway. (PubMed, Oncogene) - "Several treatment modalities can be potentially exploited to restore APM signaling in tumors, which improves anti-tumor immunity through the activation of interferons, vaccines or rimantadine against HPV and the inhibition of EGFR, SHP-2, PI3K and MEK...Therapeutic approaches to restore the MHC-I antigen presentation machinery in Head and Neck Cancer. (Red color texts represent the according strategies and the outcomes)."

IO biomarker • Journal • Review • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EGFR

Drug repurposing of rimantadine for treatment of cancer. (PubMed, Pharm Pat Anal) - "Patent US2021330605 describes the use of rimantadine, an adamantane derivative, for the treatment of melanoma, breast cancer and head and neck squamous cell carcinoma. Rimantadine inhibited proliferation of cell lines of melanoma, breast cancer, and head and neck squamous cell carcinoma, increased the survival of mice injected with cancer cell lines and restores the expression of MHC class I. Rimantadine has the potential to be used successfully in the treatment of head and neck squamous cell carcinoma."

Journal • Breast Cancer • Head and Neck Cancer • Infectious Disease • Influenza • Melanoma • Oncology • Respiratory Diseases • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

In Situ Spectroscopic Detection of Large-Scale Reorientations of Transmembrane Helices During Influenza A M2 Channel Opening. (PubMed, Angew Chem Int Ed Engl) - "This mechanical motion is impeded upon addition of the inhibitor rimantadine, giving a direct spectroscopic marker to test antiviral activity. The presented approach provides a spectroscopic tool to quantify large-scale structural changes and to track the function and inhibition of the growing number of viroporins from pathogenic viruses in future studies."

Journal • Infectious Disease • Influenza • Respiratory Diseases

Metabolic profiling to evaluate the impact of amantadine and rimantadine on the secondary metabolism of a model organism. (PubMed, Sci Rep) - "Chemometric tools were employed to find marker compounds that can be defined as characteristic indicators of a pharmacological response to a therapeutic intervention. An improved understanding of the mechanisms involved in drug effect and an increased ability to predict individual variations in the drug response of organisms will improve the treatment process and the development of new therapies."

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