Antiviral Activity of Micafungin and Its Derivatives against SARS-CoV-2 RNA Replication

Nakajima, Sachiko; Ohashi, Hirofumi; Akazawa, Daisuke; Torii, Shiho; Suzuki, Rigel; Fukuhara, Takasuke; Watashi, Koichi

doi:10.3390/v15020452

Cited by 4 publications

(4 citation statements)

References 33 publications

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“…In addition, studies have started to tie Micafungin with respiratory antiviral inhibition. A recent study tested the antiviral effects of Micafungin against the SARS-CoV-2 Wuhan strain with an IC 50 of 26.1 µM [ 42 ]. Therefore, we believe that Micafungin shows a strong indication to be a potential broad-spectrum antiviral due to precedent cases involving antiviral activities toward other respiratory viruses and with this study.…”

Section: Discussionmentioning

confidence: 99%

In Silico Identification and In Vitro Validation of Repurposed Compounds Targeting the RSV Polymerase

Park

Calderón

et al. 2023

Microorganisms

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Respiratory Syncytial Virus (RSV) is the top cause of infant hospitalization globally, with no effective treatments available. Researchers have sought small molecules to target the RNA-dependent RNA Polymerase (RdRP) of RSV, which is essential for replication and transcription. Based on the cryo-EM structure of the RSV polymerase, in silico computational analysis including molecular docking and the protein-ligand simulation of a database, including 6554 molecules, is currently undergoing phases 1–4 of clinical trials and has resulted in the top ten repurposed compound candidates against the RSV polymerase, including Micafungin, Totrombopag, and Verubecestat. We performed the same procedure to evaluate 18 small molecules from previous studies and chose the top four compounds for comparison. Among the top identified repurposed compounds, Micafungin, an antifungal medication, showed significant inhibition and binding affinity improvements over current inhibitors such as ALS-8112 and Ribavirin. We also validated Micafungin’s inhibition of the RSV RdRP using an in vitro transcription assay. These findings contribute to RSV drug development and hold promise for broad-spectrum antivirals targeting the non-segmented negative-sense (NNS) RNA viral polymerases, including those of rabies (RABV) and Ebola (EBOV).

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Section: Discussionmentioning

confidence: 99%

In Silico Identification and In Vitro Validation of Repurposed Compounds Targeting the RSV Polymerase

Park

Calderón

et al. 2023

Microorganisms

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“…VeroE6/TMPRSS2 cells, VeroE6 cells overexpressing the transmembrane serine protease 2 gene, were cultured at 37 °C in 5% CO 2 , as previously described [ 15 ].…”

Section: Methodsmentioning

confidence: 99%

“…Viral RNA was extracted using a MagMAX Viral/Pathogen II Nucleic Acid Isolation Kit (Thermo Fisher Scientific, Waltham, MA, USA) and quantified by real-time reverse-transcription polymerase chain reaction (RT-PCR) analysis with a one-step quantitative RT-PCR kit (THUNDERBIRD™ Probe One-step qRT-PCR kit, Toyobo, Osaka, Japan) as previously described [ 15 ].…”

Section: Methodsmentioning

confidence: 99%

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Anti-SARS-CoV-2 Agents in Artemisia Endophytic Fungi and Their Abundance in Artemisia vulgaris Tissue

Maehara,

Nakajima,

Watashi

et al. 2023

JoF

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Coronavirus disease 2019 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therapeutic agents for the disease are being developed. Endophytes are diverse and produce various secondary metabolites and bioactive substances. We isolated 13 endophytes from the leaves and stems of Artemisia vulgaris. Antiviral testing using the culture extracts of these endophytic fungi revealed that five isolates effectively inhibited the replication of SARS-CoV-2. These extracts were used to study the inhibitory effect of SARS-CoV-2 on 3C-like protease, and two isolates proved useful. Both isolates were from the genus Colletotrichum; therefore, the percentage of Artemisia endophytic fungi in the plant tissue was observed to be an important factor in plant site selection. Thus, we conducted a macroanalysis using next-generation sequencing to analyze the percentage of endophytes in the stems (whole, skin, and inner), leaves, roots, and cultivating soil, as well as to determine the location of each genus. To the best of our knowledge, this study is the first to report that Colletotrichum spp. are abundant in stems and that stem-based methods are the most efficient for isolating endophytes targeting Colletotrichum spp.

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The structure of lipopeptides impacts their antiviral activity and mode of action against SARS-CoV-2 in vitro

Hoste,

Smeralda,

Cugnet

et al. 2024

Appl Environ Microbiol

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Microbial lipopeptides are synthesized by nonribosomal peptide synthetases and are composed of a hydrophobic fatty acid chain and a hydrophilic peptide moiety. These structurally diverse amphiphilic molecules can interact with biological membranes and possess various biological activities, including antiviral properties. This study aimed to evaluate the cytotoxicity and antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) of 15 diverse lipopeptides to understand their structure-activity relationships. Non-ionic lipopeptides were generally more cytotoxic than charged ones, with cationic lipopeptides being less cytotoxic than anionic and non-ionic variants. At 100 µg/mL, six lipopeptides reduced SARS-CoV-2 RNA to undetectable levels in infected Vero E6 cells, while six others achieved a 2.5- to 4.1-log reduction, and three had no significant effect. Surfactin, white line-inducing principle (WLIP), fengycin, and caspofungin emerged as the most promising anti-SARS-CoV-2 agents. Detailed analysis revealed that these four lipopeptides affected various stages of the viral life cycle involving the viral envelope. Surfactin and WLIP significantly reduced viral RNA levels in replication assays, comparable to neutralizing serum. Surfactin uniquely inhibited viral budding, while fengycin impacted viral binding after pre-infection treatment of the cells. Caspofungin demonstrated a lower antiviral effect compared to the others. Key structural traits of lipopeptides influencing their cytotoxic and antiviral activities were identified. Lipopeptides with a high number of amino acids, especially charged (preferentially anionic) amino acids, showed potent anti-SARS-CoV-2 activity. This research paves the way for designing new lipopeptides with low cytotoxicity and high antiviral efficacy, potentially leading to effective treatments. IMPORTANCE This study advances our understanding of how lipopeptides, which are molecules mostly produced by bacteria, with both fat and protein components, can be used to fight viruses like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). By analyzing 15 different lipopeptides, researchers identified key structural features that make some of these molecules particularly effective at reducing viral levels while being less harmful to cells. Specifically, lipopeptides with certain charged amino acids were found to have the strongest antiviral effects. This research lays the groundwork for developing new antiviral treatments that are both potent against viruses and safe for human cells, offering hope for better therapeutic options in the future.

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Antiviral Activity of Micafungin and Its Derivatives against SARS-CoV-2 RNA Replication

Cited by 4 publications

References 33 publications

In Silico Identification and In Vitro Validation of Repurposed Compounds Targeting the RSV Polymerase

In Silico Identification and In Vitro Validation of Repurposed Compounds Targeting the RSV Polymerase

Anti-SARS-CoV-2 Agents in Artemisia Endophytic Fungi and Their Abundance in Artemisia vulgaris Tissue

The structure of lipopeptides impacts their antiviral activity and mode of action against SARS-CoV-2 in vitro

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