Screening and evaluation of potential inhibitors against vaccinia virus from 767 approved drugs

Wu, Jiajing; Liu, Qiang; Xie, Hui; Chen, Ruifeng; Huang, Weijin; Liang, Chunnan; Xiao, Xinyue; Yu, Yongxin; Wang, Youchun

doi:10.1002/jmv.25544

Cited by 10 publications

(12 citation statements)

References 33 publications

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“…The VACV challenge model based on firefly luciferase expression 23 was used to assess the protection of mRNA-A-LNP and mRNA-B-LNP in mice. First, we investigated the passive protection of mRNA-A-LNP and mRNA-B-LNP immunized mouse sera (NT 50 : 6,284; 5,057), with sera from naive mice serving as negative controls.…”

Section: Resultsmentioning

confidence: 99%

Monkeypox virus quadrivalent mRNA vaccine induces antibody responses and cellular immunity and protects mice against Vaccinia virus

Sang

Zhang

Liu

et al. 2022

Preprint

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There is an urgent need for efficient and safe vaccines against the monkeypox virus (MPXV) in response to the rapidly spreading monkeypox epidemic. In the age of COVID-19, mRNA vaccines have been highly successful and emerged as platforms enabling rapid development and large-scale preparation. Here, we have developed two MPXV quadrivalent mRNA vaccines, named mRNA-A-LNP and mRNA-B-LNP, based on two IMVs (A29L and M1R) and two EEVs (A35R and B6R). By administering mRNA-A-LNP and mRNA-B-LNP intramuscularly twice, mice have induced MPXV-specific IgG antibodies and potent Vaccinia virus (VACV)-specific neutralizing antibodies. Additionally, it elicited durable MPXV-specific killer memory T-cell immunity as well as memory B-cell immunity in mice. Furthermore, the passive transfer of sera from mRNA-A-LNP and mRNA-B-LNP-immunized mice protected nude mice against the VACV challenge. In addition, two doses of mRNA-A-LNP and mRNA-B-LNP were also protective against the VACV challenge in mice. Overall, our results demonstrated that mRNA-A-LNP and mRNA-B-LNP appear to be safe and effective vaccine candidates against monkeypox epidemics, as well as against outbreaks caused by other orthopoxviruses, including the smallpox virus.

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Section: Resultsmentioning

confidence: 99%

Monkeypox virus quadrivalent mRNA vaccine induces antibody responses and cellular immunity and protects mice against Vaccinia virus

Sang

Zhang

Liu

et al. 2022

Preprint

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“…The other identified compounds did not show inhibition of viral infection in vivo. Interestingly, tranilast has been previously reported to have anti-smallpox activity (Wu et al, 2019), and it presented the highest anti-HAdV5 potency in vitro (SI > 75), but the compound did not show the expected efficacy in vivo. Several factors, such as the type of formulation, drug-enzyme interactions, or even interspecies differences in gastrointestinal adsorption, may affect drug efficacy.…”

Section: Discussionmentioning

confidence: 97%

High-Throughput Screening and Identification of Human Adenovirus Type 5 Inhibitors

Wen

Zhang

Zhao

et al. 2021

Front. Cell. Infect. Microbiol.

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Human adenovirus infections can develop into diffuse multi-organ diseases in young children and immunocompromised patients, and severe cases can lead to death. However, there are no approved antiviral drugs available to treat adenovirus diseases. In this study, a chemiluminescence-based, high-throughput screening (HTS) assay was developed and applied to screen human adenovirus 5(HAdV5)inhibitors from 1,813 approved drug library and 556 traditional Chinese medicine-sourced small-molecule compounds. We identified three compounds with in vitro anti-HAdV5 activities in the low-micromolar range (EC50 values 0.3-4.5 μM, selectivity index values 20-300) that also showed inhibitory effects on HAdV3. Cardamomin (CDM) had good anti-HAdV5 activity in vitro. Furthermore, three dilutions of CDM (150, 75, and 37.5 mg/kg/d) administered to BALB/c mouse models inhibited HAdV5-fluc infection at 1 day post-infection by 80% (p < 0.05), 76% (p < 0.05), and 58% (p < 0.05), respectively. HE-staining of pathological tissue sections of mice infected with a wildtype adenoviral strain showed that CDM had a protective effect on tissues, especially in the liver, and greatly inhibited virus-induced necrosis of liver tissue. Thus, CDM inhibits adenovirus replication in vivo and in vitro. This study established a high-throughput screening method for anti-HAdV5 drugs and demonstrated CDM to be a candidate for HAdV5 therapy, potentially providing a new treatment for patients infected with adenoviruses.

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“…It has been used in the treatment of inflammatory disease and several disease conditions including fibrosis and cardiovascular diseases and cancers. However, few studies reported an antiviral role for tranilast [ 23 ]. Although the concentration of tranilast used for the anti-HBV assay in this study is within the peak concentration in plasma after therapeutic dosage in patients (30–300 μM) [ 24 ], a relatively high dose (50–100 μM) was required to exert anti-HBV activity using hepatocyte culture compared to the tumor cell line ( Figure 2 and Figure 3 , Supplementary Figure S3 ).…”

Section: Discussionmentioning

confidence: 99%

Antiviral Compounds Screening Targeting HBx Protein of the Hepatitis B Virus

Nakamoto

et al. 2022

IJMS

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A functional cure of hepatitis B virus (HBV) infection or HB antigen loss is rarely achieved by nucleos(t)ide analogs which target viral polymerase. HBx protein is a regulatory protein associated with HBV replication. We thought to identify antiviral compounds targeting HBx protein by analyzing HBx binding activity. Recombinant GST-tagged HBx protein was applied on an FDA-approved drug library chip including 1018 compounds to determine binding affinity by surface plasmon resonance imaging (SPRi) using a PlexArray HT system. GST protein alone was used for control experiments. Candidate compounds were tested for anti-HBV activity as well as cell viability using HepG2.2.15.7 cells and HBV-infected human hepatocytes. Of the 1018 compounds screened, 24 compounds showed binding to HBx protein. Of the top 6 compounds with high affinity to HBx protein, tranilast was found to inhibit HBV replication without affecting cell viability using HepG2.2.15.7 cells. Tranilast also inhibited HBV infection using cultured human hepatocytes. Tranilast reduced HB antigen level dose-dependently. Overall, theSPRi screening assay identified novel drug candidates targeting HBx protein. Tranilast and its related compounds warrant further investigation for the treatment of HBV infection.

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Screening and evaluation of potential inhibitors against vaccinia virus from 767 approved drugs

Cited by 10 publications

References 33 publications

Monkeypox virus quadrivalent mRNA vaccine induces antibody responses and cellular immunity and protects mice against Vaccinia virus

Monkeypox virus quadrivalent mRNA vaccine induces antibody responses and cellular immunity and protects mice against Vaccinia virus

High-Throughput Screening and Identification of Human Adenovirus Type 5 Inhibitors

Antiviral Compounds Screening Targeting HBx Protein of the Hepatitis B Virus

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