tetano
Editor, Senior Moderator
J Infect Chemother
. 2024 Jun 26:S1341-321X(24)00168-5.
doi: 10.1016/j.jiac.2024.06.013. Online ahead of print. Sorbicillinoid HSL-2 inhibits the infection of influenza A virus via interaction with the PPAR-γ/NF-κB pathway
Runhong Zhou[SUP] 1 [/SUP], Ruifeng Huang[SUP] 2 [/SUP], Shaofen Zhou[SUP] 2 [/SUP], Shengsheng Lu[SUP] 2 [/SUP], Haixing Lin[SUP] 2 [/SUP], Jingnan Qiu[SUP] 2 [/SUP], Shuaiqi Ma[SUP] 2 [/SUP], Jian He[SUP] 3 [/SUP]
Affiliations
Background: Drug resistance is an important factor in the fight against influenza A virus (IAV). Natural products offer a rich source of lead compounds for the discovery of novel antiviral drugs. In a previous study, we isolated the sorbicillinoid polyketide HSL-2 from the mycelium of fungus Trichoderma sp. T-4-1. Here, we show that this compound exerts strong antiviral activity against a panel of IAVs.
Methods: The immunofluorescence and qRT-PCR assays were used to detect the inhibitory effect of HSL-2 toward the replication of influenza virus and IAV-induced expression of the pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β.
Results: The results indicated that HSL-2 inhibited influenza virus replication, and it significantly inhibited IAV-induced overexpression of the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β through modulating the PPAR-γ/NF-κB pathway. Notably, this effect was decreased when cells were transfected with PPAR-γ siRNA or treated with the PPAR-γ inhibitor T0070907. In addition, HSL-2 was able to attenuate lung inflammatory responses and to improve lung lesions in a mouse model of IAV infection.
Conclusions: In this paper, we identified a microbial secondary metabolite, HSL-2, with anti-influenza virus activity. This report is the first to describe the antiviral activity and mechanism of action of HSL-2, and it provides a new strategy for the development of novel anti-influenza virus drugs from natural sources.
Keywords: Influenza A viruses; NF-κB; PPAR-γ; inflammatory; polyketide.
. 2024 Jun 26:S1341-321X(24)00168-5.
doi: 10.1016/j.jiac.2024.06.013. Online ahead of print. Sorbicillinoid HSL-2 inhibits the infection of influenza A virus via interaction with the PPAR-γ/NF-κB pathway
Runhong Zhou[SUP] 1 [/SUP], Ruifeng Huang[SUP] 2 [/SUP], Shaofen Zhou[SUP] 2 [/SUP], Shengsheng Lu[SUP] 2 [/SUP], Haixing Lin[SUP] 2 [/SUP], Jingnan Qiu[SUP] 2 [/SUP], Shuaiqi Ma[SUP] 2 [/SUP], Jian He[SUP] 3 [/SUP]
Affiliations
- PMID: 38942291
- DOI: 10.1016/j.jiac.2024.06.013
Background: Drug resistance is an important factor in the fight against influenza A virus (IAV). Natural products offer a rich source of lead compounds for the discovery of novel antiviral drugs. In a previous study, we isolated the sorbicillinoid polyketide HSL-2 from the mycelium of fungus Trichoderma sp. T-4-1. Here, we show that this compound exerts strong antiviral activity against a panel of IAVs.
Methods: The immunofluorescence and qRT-PCR assays were used to detect the inhibitory effect of HSL-2 toward the replication of influenza virus and IAV-induced expression of the pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β.
Results: The results indicated that HSL-2 inhibited influenza virus replication, and it significantly inhibited IAV-induced overexpression of the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β through modulating the PPAR-γ/NF-κB pathway. Notably, this effect was decreased when cells were transfected with PPAR-γ siRNA or treated with the PPAR-γ inhibitor T0070907. In addition, HSL-2 was able to attenuate lung inflammatory responses and to improve lung lesions in a mouse model of IAV infection.
Conclusions: In this paper, we identified a microbial secondary metabolite, HSL-2, with anti-influenza virus activity. This report is the first to describe the antiviral activity and mechanism of action of HSL-2, and it provides a new strategy for the development of novel anti-influenza virus drugs from natural sources.
Keywords: Influenza A viruses; NF-κB; PPAR-γ; inflammatory; polyketide.