ArticlemBio2021
A Vimentin-Targeting Oral Compound with Host-Directed Antiviral and Anti-Inflammatory Actions Addresses Multiple Features of COVID-19 and Related Diseases.
Article in mBio, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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The trial behind it
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- Modulating Vimentin: A Systems-Level Therapeutic Strategy for Sepsis and Complex Diseases.Life (Basel, Switzerland) · 2026Article
- Fertility and Early Embryonic Development Toxicity of hzVSF-v13 in Sprague-Dawley Rats.Journal of applied toxicology : JAT · 2026Article
- Evaluation of the cardiopulmonary effects of repurposed COVID-19 therapeutics in healthy rats.Scientific reports · 2026Article
- Vimentin Dynamics in Viral Infection: Shield or Sabotage?International journal of molecular sciences · 2025Review
- Oral Treatment with the Vimentin-Targeting Compound ALD-R491 Mitigates Hyperinflammation, Multi-Organ Injury, and Mortality in CLP-Induced Septic Mice.Life (Basel, Switzerland) · 2025Article
- Molecular mechanisms of SARS-CoV-2 entry: implications for biomedical strategies.Microbiology and molecular biology reviews : MMBR · 2025Review
- Interferon-induced MXB protein restricts vimentin-dependent viral infection.Acta pharmaceutica Sinica. B · 2024Article
- Targeting vimentin: a multifaceted approach to combatting cancer metastasis and drug resistance.Cancer metastasis reviews · 2024Review
- Salivary IgA and vimentin differentiate in vitro SARS-CoV-2 infection: A study of 290 convalescent COVID-19 patients.Mucosal immunology · 2024Article
- The molecular biophysics of extracellular vimentin and its role in pathogen-host interactions.Current opinion in cell biology · 2023Review
- Atractylodinol prevents pulmonary fibrosis through inhibiting TGF-β receptor 1 recycling by stabilizing vimentin.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Coronavirus and the Cytoskeleton of Virus-Infected Cells.Sub-cellular biochemistry · 2023Article
- Current state-of-the-art and potential future therapeutic drugs against COVID-19.Frontiers in cell and developmental biology · 2023Review
- Vimentin: from a cytoskeletal protein to a critical modulator of immune response and a target for infection.Frontiers in immunology · 2023Review
- Research and development of Chinese anti-COVID-19 drugs.Acta pharmaceutica Sinica. B · 2022Review
- Article
- Double-Blind, Randomized, Placebo-Controlled Study on hzVSF-v13, a Novel Anti-Vimentin Monoclonal Antibody Drug as Add-on Standard of Care in the Management of Patients with Moderate to Severe COVID-19.Journal of clinical medicine · 2022Article
- ALD-R491 regulates vimentin filament stability and solubility, cell contractile force, cell migration speed and directionality.Frontiers in cell and developmental biology · 2022Article
- The multifaceted roles of NLRP3-modulating proteins in virus infection.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
19 authors at 2 institutions in 1 country.
Funding
Abstract
Damage in COVID-19 results from both the SARS-CoV-2 virus and its triggered overactive host immune responses. Therapeutic agents that focus solely on reducing viral load or hyperinflammation fail to provide satisfying outcomes in all cases. Although viral and cellular factors have been extensively profiled to identify potential anti-COVID-19 targets, new drugs with significant efficacy remain to be developed. Here, we report the potent preclinical efficacy of ALD-R491, a vimentin-targeting small molecule compound, in treating COVID-19 through its host-directed antiviral and anti-inflammatory actions. We found that by altering the physical properties of vimentin filaments, ALD-491 affected general cellular processes as well as specific cellular functions relevant to SARS-CoV-2 infection. Specifically, ALD-R491 reduced endocytosis, endosomal trafficking, and exosomal release, thus impeding the entry and egress of the virus; increased the microcidal capacity of macrophages, thus facilitating the pathogen clearance; and enhanced the activity of regulatory T cells, therefore suppressing the overactive immune responses. In cultured cells, ALD-R491 potently inhibited the SARS-CoV-2 spike protein and human ACE2-mediated pseudoviral infection. In aged mice with ongoing, productive SARS-CoV-2 infection, ALD-R491 reduced disease symptoms as well as lung damage. In rats, ALD-R491 also reduced bleomycin-induced lung injury and fibrosis. Our results indicate a unique mechanism and significant therapeutic potential for ALD-R491 against COVID-19. We anticipate that ALD-R491, an oral, fast-acting, and non-cytotoxic agent targeting the cellular protein with multipart actions, will be convenient, safe, and broadly effective, regardless of viral mutations, for patients with early- or late-stage disease, post-COVID-19 complications, and other related diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.