scholarly journals Host-directed FDA-approved drugs with antiviral activity against SARS-CoV-2 identified by hierarchical in silico/in vitro screening methods

2020 ◽  
Author(s):  
Tiziana Ginex ◽  
Urtzi Garaigorta ◽  
David Ramírez ◽  
Victoria Castro ◽  
Vanesa Nozal ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Viral Entry ◽  
In Silico ◽  
Drug Repurposing ◽  
Screening Methods ◽  
Speed Up ◽  
Approved Drugs ◽  
Fda Approved Drugs ◽  
Virtual Screening Approach

AbstractThe unprecedent situation generated by the COVID-19 global emergency has prompted scientists around the world to actively work to fight against this pandemic. In this sense, it is remarkable the number of drug repurposing efforts trying to shed light into the COVID-19 patients’ treatment.In the attempt to proceed toward a proper rationalization of the search for new antivirals among approved drugs, we carried out a hierarchical in silico/in vitro protocol which successfully combines virtual and biological screening to speed up the identification of host-directed therapies against COVID-19 in an effective way.A successful combination of a multi-target virtual screening approach focused on host-based targets related to viral entry and experimental evaluation of the antiviral activity of selected compounds has been carried out. As a result, three different potentially repurposable drugs interfering with viral entry, cepharantine, imatinib and efloxate, have been identified.

scholarly journals Host-Directed FDA-Approved Drugs with Antiviral Activity against SARS-CoV-2 Identified by Hierarchical In Silico/In Vitro Screening Methods

2021 ◽  
Vol 14 (4) ◽  
pp. 332
Author(s):  
Tiziana Ginex ◽  
Urtzi Garaigorta ◽  
David Ramírez ◽  
Victoria Castro ◽  
Vanesa Nozal ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Viral Entry ◽  
In Silico ◽  
Screening Methods ◽  
Speed Up ◽  
Approved Drugs ◽  
Fda Approved Drugs ◽  
Shed Light ◽  
Virtual Screening Approach

The unprecedent situation generated by the COVID-19 global emergency has prompted us to actively work to fight against this pandemic by searching for repurposable agents among FDA approved drugs to shed light into immediate opportunities for the treatment of COVID-19 patients. In the attempt to proceed toward a proper rationalization of the search for new antivirals among approved drugs, we carried out a hierarchical in silico/in vitro protocol which successfully combines virtual and biological screening to speed up the identification of host-directed therapies against COVID-19 in an effective way. To this end a multi-target virtual screening approach focused on host-based targets related to viral entry, followed by the experimental evaluation of the antiviral activity of selected compounds, has been carried out. As a result, five different potentially repurposable drugs interfering with viral entry—cepharantine, clofazimine, metergoline, imatinib and efloxate—have been identified.

scholarly journals Broad anti-coronaviral activity of FDA approved drugs against SARS-CoV-2 in vitro and SARS-CoV in vivo

2020 ◽  
Author(s):  
Stuart Weston ◽  
Christopher M. Coleman ◽  
Rob Haupt ◽  
James Logue ◽  
Krystal Matthews ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Rapid Development ◽  
Drug Repurposing ◽  
Ic50 Values ◽  
Human Use ◽  
Approved Drugs ◽  
Fda Approved Drugs

AbstractSARS-CoV-2 emerged in China at the end of 2019 and has rapidly become a pandemic with roughly 2.7 million recorded COVID-19 cases and greater than 189,000 recorded deaths by April 23rd, 2020 (www.WHO.org). There are no FDA approved antivirals or vaccines for any coronavirus, including SARS-CoV-2. Current treatments for COVID-19 are limited to supportive therapies and off-label use of FDA approved drugs. Rapid development and human testing of potential antivirals is greatly needed. A quick way to test compounds with potential antiviral activity is through drug repurposing. Numerous drugs are already approved for human use and subsequently there is a good understanding of their safety profiles and potential side effects, making them easier to fast-track to clinical studies in COVID-19 patients. Here, we present data on the antiviral activity of 20 FDA approved drugs against SARS-CoV-2 that also inhibit SARS-CoV and MERS-CoV. We found that 17 of these inhibit SARS-CoV-2 at a range of IC50 values at non-cytotoxic concentrations. We directly follow up with seven of these to demonstrate all are capable of inhibiting infectious SARS-CoV-2 production. Moreover, we have evaluated two of these, chloroquine and chlorpromazine, in vivo using a mouse-adapted SARS-CoV model and found both drugs protect mice from clinical disease.

In Silico Modeling of FDA-Approved Drugs for Discovery of Therapies Against Neglected Diseases: A Drug Repurposing Approach

2019 ◽  
pp. 625-648 ◽  
Author(s):  
Carolina L. Belllera ◽  
María L. Sbaraglini ◽  
Lucas N. Alberca ◽  
Juan I. Alice ◽  
Alan Talevi
Keyword(s):  
In Silico ◽  
Drug Repurposing ◽  
Neglected Diseases ◽  
In Silico Modeling ◽  
Approved Drugs ◽  
Fda Approved Drugs

scholarly journals Sulfisoxazole does not inhibit the secretion of small extracellular vesicles

2020 ◽  
Author(s):  
Pamali Fonseka ◽  
Sai V Chitti ◽  
Rahul Sanwlani ◽  
Suresh Mathivanan
Keyword(s):  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Breast Cancer Cells ◽  
Drug Repurposing ◽  
Tumor Burden ◽  
Immunocompetent Mouse ◽  
Approved Drugs ◽  
Fda Approved Drugs

AbstractRecently, the study by Im et al. focused on blocking the release of extracellular vesicles (EVs) by cancer cells, as a strategy to block metastasis, by deploying a drug repurposing screen. Upon screening the library of FDA approved drugs in breast cancer cells in vitro, the authors reported the ability of the antibiotic Sulfisoxazole (SFX) in inhibiting EV biogenesis and secretion. SFX was also effective in reducing breast primary tumor burden and blocking metastasis in immunocompromised and immunocompetent mouse models. As we seek a compound to block EV biogenesis and secretion in our current in vivo studies, we intended to use SFX and hence performed in vitro characterization as the first step. However, treatment of two cancer cells with SFX did not reduce the amount of EVs as reported by the authors.

scholarly journals Drug Repurposing Commonly Against Dengue Virus Capsid and SARS-CoV-2 Nucleocapsid: An in Silico Approach

2020 ◽  
Author(s):  
Debica Mukherjee ◽  
Rupesh Roy ◽  
UPASANA RAY
Keyword(s):  
Dengue Virus ◽  
Capsid Protein ◽  
In Silico ◽  
Rna Binding ◽  
Drug Repurposing ◽  
Virus Capsid ◽  
Approved Drugs ◽  
Full Swing ◽  
Fda Approved Drugs ◽  
Virus Capsid Protein

<p></p><p>In the middle of SARS-CoV-2 pandemic, dengue virus (DENV) is giving a silent warning as the season approaches nearer. There is no specific antiviral against DENV for use in the clinics. Thus, considering these facts we can potentially face both these viruses together increasing the clinical burden. The search for anti-viral drugs against SARS-CoV-2 is in full swing and repurposing of already ‘in-use’ drugs against other diseases or COVID-19 has drawn significant attention. Earlier we had reported few FDA approved anti-viral and anti-microbial drugs that could be tested for binding with SARS-CoV-2 nucleocapsid N terminal domain. We explored the possibility of interactions of the drugs screened for SARS-CoV2 with Dengue virus capsid protein. We report five FDA approved drugs that were seen to be docking onto the SARS-CoV-2 nucleocapsid RNA binding domain, also docking well with DENV capsid protein on the RNA binding site and/or the capsid’s membrane fusion domain. Thus, the present study proposes these five drugs as common antiviral candidates against both SARS-CoV-2 and DENV although the <i>in silico</i> study is subject to further validations.</p><br><p></p>

scholarly journals Repurposing inhibitors for SARS-CoV2 main protease

2020 ◽  
Author(s):  
Kumar Sharp
Keyword(s):  
Viral Replication ◽  
Active Sites ◽  
Drug Repurposing ◽  
Chemotherapeutic Drugs ◽  
Short Term ◽  
Main Protease ◽  
Potential Binding ◽  
Approved Drugs ◽  
Fda Approved Drugs

Abstract SARS-CoV2 main protease is important for viral replication and one of the most potential targets for drug development in this current pandemic. Drug repurposing is a promising field to provide potential short-term acceptable therapy for management of coronavirus till a specific anti-viral for coronavirus is developed. In-silico drug repurposing screening is the current fastest way to repurpose drugs by targeting active sites in fraction of seconds. In this study, SARS-CoV2 main protease is being targeted by 1050 FDA-approved drugs to inhibit its activity thereby interfering with viral replication. Chemotherapeutic drugs and anti-retroviral drugs have shown potential binding as inhibitor. In-vitro and clinical trials required to establish final fact.

scholarly journals Heparan sulfate assists SARS-CoV-2 in cell entry and can be targeted by approved drugs in vitro

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Qi Zhang ◽  
Catherine Zhengzheng Chen ◽  
Manju Swaroop ◽  
Miao Xu ◽  
Lihui Wang ◽  
...  
Keyword(s):  
Cell Surface ◽  
Heparan Sulfate ◽  
Viral Entry ◽  
Drug Repurposing ◽  
Cell Entry ◽  
Entry Pathway ◽  
Viral Particles ◽  
Approved Drugs ◽  
Attachment Factor

Abstract The cell entry of SARS-CoV-2 has emerged as an attractive drug repurposing target for COVID-19. Here we combine genetics and chemical perturbation to demonstrate that ACE2-mediated entry of SARS-Cov and CoV-2 requires the cell surface heparan sulfate (HS) as an assisting cofactor: ablation of genes involved in HS biosynthesis or incubating cells with a HS mimetic both inhibit Spike-mediated viral entry. We show that heparin/HS binds to Spike directly, and facilitates the attachment of Spike-bearing viral particles to the cell surface to promote viral entry. We screened approved drugs and identified two classes of inhibitors that act via distinct mechanisms to target this entry pathway. Among the drugs characterized, Mitoxantrone is a potent HS inhibitor, while Sunitinib and BNTX disrupt the actin network to indirectly abrogate HS-assisted viral entry. We further show that drugs of the two classes can be combined to generate a synergized activity against SARS-CoV-2-induced cytopathic effect. Altogether, our study establishes HS as an attachment factor that assists SARS coronavirus cell entry and reveals drugs capable of targeting this important step in the viral life cycle.

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