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 3 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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Implications of empirical administration of caspofungin in COVID-19 complicated fungal infections

Itoh,

Tsutani,

Mitsuke

et al. 2023

Front. Cell. Infect. Microbiol.

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SARS-CoV-2 infection and fungal infectionsCandida and Aspergillus spp. were identified as the most common causes of invasive fungal infections in COVID-19 patients (Ezeokoli and Pohl, 2020). The mortality rate of invasive Candida infections was twice as high in COVID-19 patients as in non-COVID-19 patients (Seagle et al., 2022). Therefore, prevention of the complications of fungal infections in COVID-19 is a crucial issue with implications for prognosis. Risk factors for COVID-19-associated candidiasisYazdanpanah S et al. analyzed risk factors for COVID-19-associated candidiasis (Yazdanpanah et al., 2023). They used multiple logistic regression to show that heart failure, bacterial co-infection, and empiric antifungal use were significant risk factors for Candida co-infection in hospitalized COVID-19 patients (Yazdanpanah et al., 2023). In their study, azoles were used for empirical antifungal treatment, and in some cases, azoles were used in combination with the echinocandin antifungal agent caspofungin. The antifungal effects seem to differ among these drugs. While some Candida strains were resistant to azoles, caspofungin was effective against all isolated strains in that study (Yazdanpanah et al., 2023). In addition, the study found higher odds of in-hospital mortality in Candida culture-positive patients (RR: 2.18, 95% CI: 0.9, 5.2) (Yazdanpanah et al., 2023), but no subgroup analysis classified by empiric therapy was performed. We believe that this study should elucidate whether empirical caspofungin treatment can improve prognosis in a cohort of COVID-19 patients with risk factors for fungal infection complications.

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

Cited by 3 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

Implications of empirical administration of caspofungin in COVID-19 complicated fungal infections

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