Screening of a Small Molecule Compound Library Identifies Toosendanin as an Inhibitor Against Bunyavirus and SARS-CoV-2

Abstract

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne virus causing serious infectious disease with a high case-fatality of up to 50% in severe cases. Currently, no effective drug has been approved for the treatment of SFTSV infection. Here, we performed a high-throughput screening of a natural extracts library for compounds with activities against SFTSV infection. Three hit compounds, notoginsenoside Ft1, punicalin, and toosendanin were identified for displaying high anti-SFTSV efficacy, in which, toosendanin showed the highest inhibition potency. Mechanistic investigation indicated that toosendanin inhibited SFTSV infection at the step of virus internalization. The anti-viral effect of toosendanin against SFTSV was further verified in mouse infection models, and the treatment with toosendanin significantly reduced viral load and histopathological changes in vivo. The antiviral activity of toosendanin was further expanded to another bunyavirus and the emerging SARS-CoV-2. This study revealed a broad anti-viral effect of toosendanin and indicated its potential to be developed as an anti-viral drug for clinical use.

Saikosaponin B2, Punicalin, and Punicalagin in Vitro Block Cellular Entry of Feline Herpesvirus-1

“…Punicalin and Punicalagin, both derived from pomegranate extracts, are structurally polyphenolic compounds, and they exhibit antiviral activities similar to Saikosaponin B2. They have demonstrated effectiveness against the hepatitis C virus, SARS-CoV-2, and influenza virus [ 26 , 27 , 28 , 29 ]. Additionally, these compounds have shown the capacity to reduce inflammatory damage, with animal models revealing no adverse effects on the health of rats [ 30 , 31 ].…”

Toosendanin activates caspase-1 and induces maturation of IL-1β to inhibit type 2 porcine reproductive and respiratory syndrome virus replication via an IFI16-dependent pathway

“…Previous research indicated that TSN possesses broad biological activities, such as blocking acetylcholine release, and anti-botulismic, and anti-tumor effects [47,48]. Importantly, TSN was reported to inhibit infections of viruses such as HCV [38], IAV [37], SFTSV and SARS-CoV-2 [39]. However, these studies mainly focused on TSN antiviral activities rather than its mechanisms of action.…”

“…After that, TSN was reported to possess anticancer activities by inducing apoptosis in various cancer cells [34][35][36]. In recent years, TSN was reported to have antiviral activities against IAV [37], hepatitis C virus (HCV) [38], severe fever with thrombocytopenia syndrome virus (SFTSV) and SARS-CoV-2 [39]. However, the molecular mechanism of action for TSN against these viral infections remains poorly understood.…”

Computer-Selected Antiviral Compounds: Assessing In Vitro Efficacies against Rift Valley Fever Virus

“…Many small molecules have been identified as potent inhibitors of RVFV, each acting through distinct mechanisms [ 5 ]. These include nucleoside analogs (Ribavirin, Favipiravir, BCX4430, 6-azauridine) [ 6 , 7 , 8 ]; an oxidizer of viral lipid membranes (LJ001) [ 9 ]; an inhibitor of viral RNA replication and egress (Sorafenib) [ 10 ]; inhibitors of viral entry and/or RNA synthesis (E225-0969, E528-0039, G118-0778, G544-0735) [ 11 ]; inhibitor of post viral entry and/or RNA replication (1-N-(2-(biphenyl-4-yloxy)ethyl)propane-1,3-diamine and the derivatives) [ 12 ]; a disruptor of N-RNA binding (Suramin) [ 13 ]; an mTOR inhibitor (Rapamycin) [ 14 ]; an autophagy enhancer (SMER28) [ 15 ]; an antioxidant (NSC62914) [ 16 ]; HSP90 inhibitors (17AAG, BAPT A-AM) [ 17 ]; a Protein Phosphatase-1 inhibitor (1E7-03) [ 18 ]; a cell membrane modulator affecting viral fusion (25-hydroxycholesterol) [ 19 ]; a ubiquitin proteasome inhibitor (Bortezomib) [ 20 ]; and inhibitors with unknown mechanisms (FGI-106, 5,6-dimethoxyindan-1-one analog, mitoxantrone, toosendanin) [ 6 , 21 , 22 , 23 ].…”