Antiviral activity and mechanism of the antifungal drug, anidulafungin, suggesting its potential to promote treatment of viral diseases

Abstract

Background The severe fever with thrombocytopenia syndrome disease (SFTS), caused by the novel tick-borne SFTS virus (SFTSV), was listed among the top 10 priority infectious disease by World Health Organization due to the high fatality rate of 5–30% and the lack of effective antiviral drugs and vaccines and therefore raised the urgent need to develop effective anti-SFTSV drugs to improve disease treatment. Methods The antiviral drugs to inhibit SFTSV infection were identified by screening the library containing 1340 FDA-approved drugs using the SFTSV infection assays in vitro. The inhibitory effect on virus entry and the process of clathrin-mediated endocytosis under different drug doses was evaluated based on infection assays by qRT-PCR to determine intracellular viral copies, by Western blot to characterize viral protein expression in cells, and by immunofluorescence assays (IFAs) to determine virus infection efficiencies. The therapeutic effect was investigated in type I interferon receptor defective A129 mice in vivo with SFTSV infection, from which lesions and infection in tissues caused by SFTSV infection were assessed by H&E staining and immunohistochemical analysis. Results Six drugs were identified as exerting inhibitory effects against SFTSV infection, of which anidulafungin, an antifungal drug of the echinocandin family, has a strong inhibitory effect on SFTSV entry. It suppresses SFTSV internalization by impairing the late endosome maturation and decreasing virus fusion with the membrane. SFTSV-infected A129 mice had relieving symptoms, reduced tissue lesions, and improved disease outcomes following anidulafungin treatment. Moreover, anidulafungin exerts an antiviral effect in inhibiting the entry of other viruses including SARS-CoV-2, SFTSV-related Guertu virus and Heartland virus, Crimean-Congo hemorrhagic fever virus, Zika virus, and Herpes simplex virus 1. Conclusions The results demonstrated that the antifungal drug, anidulafungin, could effectively inhibit virus infection by interfering with virus entry, suggesting it may be utilized for the clinical treatment of infectious viral diseases, in addition to its FDA-approved use as an antifungal. The findings also suggested to further evaluate the anti-viral effects of echinocandins and their clinical importance for patients with infection of viruses, which may promote therapeutic strategies as well as treatments and improve outcomes pertaining to various viral and fungal diseases.

Computational-Aided Reproposing Drug(s) and Discovery for Potential Antivirals Targeting Hepatitis B Virus Capsid Protein

“…This suggests the potential of antifungals with common pharmacological features to have anti-HBV activities. The antiviral effects of some antifungals are shown before [26,35], indicating the potential ancestry druggable site shared in viruses and fungi that opens a vast field in the future researches.…”

Heartland Virus Disease—An Underreported Emerging Infection

“…Recent research has demonstrated that HRTV (along with other viruses) was inhibited by anidulafungin in a dose-dependent manner by interfering with the virus’s entry into cells. Anidulafungin is approved by the FDA for antifungal use [ 69 ].…”

Identification and characterization of three monoclonal antibodies targeting the SFTSV glycoprotein and displaying a broad spectrum recognition of SFTSV-related viruses

“…Liver, spleen, lungs, and kidneys were collected from mice infected with the HBGS13 strain on days 4 and 12 p.i. (n = 3 at each time point), respectively, and were fixed in 4% paraformaldehyde for 24 h. Hematoxylin-eosin (H&E) staining and immunohistochemical assays were performed to observe the pathological changes caused by SFTSV infection and to blot SFTSV infection in tissues using a pAb against SFTSV NP as previously described [29]. SFTSV RNA loads in tissues and serum samples were determined by qRT-PCR as previously showed [30].…”