ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
·
2023
·Vol. 67
·期 3
·
IF 4.9
Oluwatayo Israel Olasunkanmi,Yanru Fei,Juval Avala Ntsigouaye,Ming Yi,Yao Wang,Jinchang Liu,Weixu Cheng,James Megeto,Tahira Bashir,Yang Chen,Weizhen Xu,Lexun Lin,Wenran Zhao,Yan Wang,Zhaohua Zhong
Enterovirus infections are life-threatening viral infections which occur mainly among children and are possible causes of viral outbreak. Until now, treatment and management of infections caused by members of the genus Enterovirus largely depended on supportive care, and no antiviral medications are currently approved for the treatment of most of these infections. The urgency of discovering new therapeutic options for the treatment of enterovirus infection is increasing. In the present study, we identified that trans-2-hexenoic acid (THA), a natural product from a dietary source, possesses antiviral activity against coxsackievirus B (CVB) and enterovirus A71 (EV-A71) in a dose-dependent manner. We found that THA possesses antiviral activity at 50% effective concentrations (EC50) of 2.9 μM and 3.21 μM against CVB3 and EV-A71 infections, respectively. The time of addition assay revealed that THA inhibits both CVB3 and EV-A71 replication at the entry stage of infection. Additional results from this study further suggest that THA inhibits viral replication by blocking viral entry. Given that THA has received approval as a food additive, treatment of enterovirus infections with THA might be a safe therapeutic option or could pave the way for semisynthetic manufacturing of more antiviral drugs in the future.
研究领域:
病毒学
·
药理学
·
传染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FISH & SHELLFISH IMMUNOLOGY
·
2024
·
IF 4.1
Yanwei Zhang,Jing Cen,Haixia Wu,Wa Gao,Zhiying Jia,Mikolaj Adamek,Jun Zou
HnRNP A/B belongs to the heterogeneous nuclear ribonucleoprotein (hnRNP) family and plays an important role in regulating viral protein translation and genome replication. Here, we found that overexpression of hnRNP A/B promoted Spring viremia of carp virus (SVCV) and Cyprinid herpesvirus 3 (CyHV3) replication. Further, hnRNP A/B was shown to act as a negative regulator of type I interferon (IFN) response. Mechanistically, hnRNP A/B interacted with MITA, TBK1 and IRF3 to initiate their degradation. In addition, hnRNP A/B bound to the kinase domain of TBK1, the C terminal domain of MITA and IAD domain of IRF3, and the RRM1 domain of hnRNP A/B bound to TBK1, RRM2 domain bound to IRF3 and MITA. Our study provides novel insights into the functions of hnRNP A/B in regulating host antiviral response.
研究领域:
分子生物学
·
病毒学
·
免疫学
·
鱼类病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
·
2025
·
IF 5.4
Man Liu,Li Zhao,Xupeng Huang,Zhenhao Tang,Yihang Zhong,Mengrong Yan,Shun Liu,Shunjing Wang,Zeyun Sun,Zixuan Rao,Linyi Yu,Yuying Fang,Wei Zhang,Hongbo Zhang,Wei Peng
The COVID-19 pandemic underscores the urgent need to develop broad-spectrum antivirals against coronaviruses (CoVs) to prepare for future outbreaks. In this study, we presented a systematic approach to developing broad-spectrum Mpro inhibitors, with a focus on high-risk CoVs. We optimised S-217622 as a lead compound, with the goal of enhancing conserved interactions within the S1, S2, and S3/S4 pockets of Mpro, leading to significantly improved inhibitory potency against representative CoVs. Compound 25 exhibited submicromolar activity across all ten CoVs, with IC50 values below 0.1 μM for six of them. The X-ray co-crystal structure of SARS-CoV-2 Mpro in complex with compound 25 revealed the structural basis of conserved interactions contributing to its broad-spectrum activity. This study demonstrates the feasibility of reinforcing conserved interactions to develop Mpro inhibitors with broad-spectrum activity and provides valuable strategies for combating future pandemics caused by unknown CoVs.
研究领域:
病毒学
·
药物开发
·
结构生物学
✓ 已验证
DOI
PubMed
高影响因子
VIRUS RESEARCH
·
2018
·
IF 2.484
Chen Cheng,Shen Yu-Feng,Hu Yang,Liu Lei,Chen Wei-Chao,Wang Gao-Xue,Zhu Bin
As one of nine piscine viruses recognized by the International Office of Epizootics, spring viraemia of carp virus (SVCV) is an important pathogen bringing high mortality to cyprinids. Up to now, there is no approved therapy on SVCV, making them strong public health threat in aquaculture. In this study, the anti-SVCV activities of 12 plant crude extracts were investigated by using epithelioma papulosum cyprini (EPC) cells. Among these plants, Psoralea corylifolia Linn. showed the highest inhibition on SVCV replication, with an inhibitory percentage of 67.98%. Further studies demonstrated that bavachin (BVN), one of the major constituents of Psoralea corylifolia Linn., was also highly effective to SVCV infection. The half maximal inhibitory concentrations (IC 50 ) of BVN on SVCV glycoprotein and nucleoprotein expression were 0.46 (0.29–0.73) and 0.31 (0.13–0.55) mg/L, respectively. In addition, SVCV-induced apoptosis which may be negative to SVCV replication was inhibited by BVN. The apoptotic cells were decreased 21.42% for BVN compared with SVCV group. These results indicated that the inhibition of BVN on SVCV replication was, in some extent, via blocking SVCV induced apoptosis. Furthermore, cellular morphological damage induced by SVCV was also blocked by BVN treatment. Mechanistically, BVN did not affect SVCV infectivity and cannot be used for prevention of SVCV infection. Time-of-addition and viral binding assays revealed that BVN mainly inhibited the early events of SVCV replication but did not interfere with SVCV adsorption. In conclusion, BVN was considered to develop as a promising agent to treat SVCV infection.
研究领域:
水产养殖学
·
病毒学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELLULAR SIGNALLING
·
2018
·
IF 3.487
Wei-Chao Chen,Lei Liu,Yu-Feng Shen,Yang Hu,Fei Ling,Gao-Xue Wang,Bin Zhu
Coumarin forms an elite class of naturally occurring compounds that possess promising antiviral therapeutic perspectives. In this study, a coumarin derivative 7-[6-(2-methylimidazole) hexyloxy] coumarin (D5) was designed and synthesized to evaluate antiviral activity on a rhabdovirus , spring viraemia of carp virus (SVCV). Our results demonstrated that D5 had a robust antiviral activity with >90% inhibitory rate of SVCV expression in the host cells. And D5 significantly reduced viral-induced apoptosis and recovered virus-activated caspase-3/8/9 activities. Further data determined that SVCV could alter the cytoskeletal structure of EPC cells, characterized by a circumferential ring of microtubules and a disrupted microfilament organization, whereas cytoskeleton structure in D5-treated cells kept the normal morphology. Mechanistically speaking, D5 could interfere with SVCV replication inside or outside of cells through two different approaches. Before the process of virus entry into EPC cells, D5 had an impact on SVCV glycoprotein structure so as to disrupt viral binding to the cell surface or translocation to the cytosol. Another strategy for D5 to against SVCV was that D5 significantly suppressed SVCV-activated autophagy, which was beneficial for the host cells to restrict SVCV viral replication, accompanied by a higher phosphorylation of Akt-mTOR. In summary, our results revealed that D5 was effective in weakening SVCV infection and regulating SVCV-induced undesirable conditions, and this compound provided new therapeutic implications for the treatment of rhabdoviruses.
研究领域:
病毒学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2021
·
IF 5.279
Jian Zhang,Fangcheng He,Jixiang Chen,Yanju Wang,Yuyuan Yang,Deyu Hu,Baoan Song
To find efficient and broad-spectrum viral agents, a series of purine nucleoside derivatives containing sulfa ethylamine moieties was designed and synthesized, and their antiviral activities against tobacco mosaic virus (TMV), cucumber mosaic virus (CMV), and potato virus Y (PVY) were evaluated. Some target compounds displayed good antiviral activities. Among them, compound 3 showed excellent protective activity against CMV and PVY with 50% effective concentration values (EC50) of 137 and 209 μg/mL, respectively, which were better than that of the control agent ningnanmycin (508 and 431 μg/mL). Moreover, the EC50 value of compound 3 for the inactivating activity against TMV was 48 μg/mL, which was better than that of ningnanmycin (88 μg/mL). In addition, compound 3 not only destroyed the structure of the TMV virus but also had a good interaction with the coat protein of the TMV virus. Therefore, compound 3 may further destroy the structure of the virus by binding to the coat protein of the TMV virus, thereby weakening the infectivity of the virus.
研究领域:
药理学
·
有机化学
·
病毒学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2023
·
IF 6.1
Xiuhai Gan,Wei Zhang,Shichao Lan,Deyu Hu
To further develop new antiviral agents, several novel cyclized derivatives of ferulic acid were designed and synthesized. Their antiviral activities were evaluated against the cucumber mosaic virus (CMV), pepper mild mottle virus (PMMoV), and tomato spotted wilt virus (TSWV). The results showed that some ferulic acid derivatives exhibited desirable antiviral activities. Particularly, compound 5e exhibited excellent protective activities against CMV, PMMoV, and TSWV, with EC50 values of 167.2, 102.5, and 145.8 μg mL–1, respectively, which were superior to those obtained for trans-ferulic acid (581.7, 611.2, and 615.4 μg mL–1), dufulin (312.6, 302.5, and 298.2 μg mL–1), and ningnanmycin (264.3, 282.5, and 276.5 μg mL–1). Thereafter, the protective mechanisms of 5e were evaluated through photosynthesis evaluation, transcriptome profiling, and proteomic analysis. The results indicated that 5e significantly activated the expression levels of photosynthesis-related regulatory genes and proteins in tobacco plants and promoted the accumulation of defense molecules to resist viral infection. Thus, the findings of this study indicated that novel cyclized ferulic acid derivatives are potential antiviral agents that act via regulating photosynthesis in the host.
研究领域:
植物病理学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Virology Journal
·
2025
·Vol. 22
·期 1
·1-14
·
IF 3.8
Liu Xianglan,Hu Jiaming,Wu Jiarui,Tian Yiru,Wang Jinbo,Wu Chunyan,Chen Qingfeng,Krall Leonard,He Yanping,Lu Qun
Background Human norovirus (HNV) is the predominant pathogen causing outbreaks of acute gastroenteritis globally. Despite significant efforts to combat norovirus infections, there is currently no FDA approved vaccine or antiviral drug available. Consequently, the development of effective antiviral agents is of critical importance. Methods and results In this study, a series of 41 5-cyano-2-thiacetyl aromatic pyrimidinone compounds were designed and synthesized. A cell viability-based screening for anti-murine norovirus (MNV) compounds was conducted, revealing that compound 29 (hereafter used as Co-29) exhibited antiviral activity against MNV. Co-29 demonstrated effective inhibition of MNV CW3 RNA replication, exhibiting an EC 50 of 58.22 μM. An RdRp enzyme activity assay indicated that Co-29 directly inhibits RdRp activity to both MNV and HNV. Molecular docking studies suggested that Co-29 interacts with the palm region of RdRp via hydrogen bonding with specific residues, which are conserved in RdRps across MNV and HNV norovirus variants. Conclusions In conclusion, our study suggests that the newly synthesized Co-29 may serve as a potential antiviral candidate or lead compound for future studies.
研究领域:
病毒学
·
药物化学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Viruses-Basel
·
2022
·Vol. 14
·期 12
·2692
·
IF 5.818
Qinyan Wang,Qikai Yin,Shihong Fu,Jingxia Cheng,Xiuyan Xu,Jing Wang,Bin Wu,Xiaodong Tian,Yan Li,Jing Lu,Ying He,Fan Li,Kai Nie,Songtao Xu,Xiaoqing Lu,Huanyu Wang,Bin Wang,Guodong Liang
In Yangquan County, the sandfly-transmitted virus (Wuxiang virus) was first isolated from sandflies in 2018. However, relationships between the abundance and seasonal fluctuations of local sandflies and sandfly-transmitted viruses are unknown. Herein, we report that sandfly specimens were collected in three villages in Yangquan County, from June to August, 2019. A total of 8363 sandflies were collected (June, 7927; July, 428; August, 8). Eighteen virus strains (June, 18; July, 0; August, 0) were isolated in pools of Phlebotomus chinensis. The genome sequence of the newly isolated virus strain was highly similar to that of the Wuxiang virus (WUXV), isolated from sandflies in Yangquan County in 2018. Our results suggested that the sandfly-transmitted viruses, and the local sandfly population, are stable in Yangquan County, and that June is the peak period for the virus carried by sandflies in this area.Keywords:sandfly;Wuxiang virus;Phlebovirus;spatial and temporal distribution
研究领域:
病毒学
·
昆虫学
·
流行病学
✓ 已验证
DOI
PubMed
高影响因子
VIROLOGY
·
2023
·
IF 3.7
Xiaoyan Zheng,Ran Wang,Chenghong Yin
Dengue virus (DENV), Japanese encephalitis virus (JEV) and Zika virus (ZIKV) are the three most important flaviviruses, which can cause health problems worldwide. All these flaviviruses can cause liver damage, however, the mechanism of liver injury is still unclear. Metabolomics can give insight into the full complexity of a disease. In our study, we used an LC-MS method to analysis the metabolites in liver samples of the three flaviviruses-infected mice and the non-infected mice. Compared with the control mice, the liver of the DENV-infected, JEV-infected, and ZIKV-infected mice had 32, 34, and 55 differential metabolites. We also found that there were obvious differences in some metabolic pathways among the four groups. Metabonomic analysis of liver is very important for understanding the pathogenesis of flaviviruses.
研究领域:
病毒学
·
医学
·
代谢组学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2023
·
IF 6.1
Fangping Zhong,Qi Zhang,Kejia Chen,Shichao Lan,Wenchao Yang,Xiuhai Gan
Natural products are a crucial source in the development of new eco-friendly antiviral agents to control plant viral diseases. In our previous studies, some ferulic acid derivatives with good antiviral activity were obtained as an immune activator. To continue the discovery of eco-friendly antiviral agents, different monosaccharides were introduced into cinnamic acid skeletons by an activity-based strategy to obtain a series of cinnamic acid derivatives containing glycoside scaffolds, and their antiviral activities against tobacco mosaic virus (TMV) and tomato spotted wilt virus (TSWV) were evaluated. Among them, compound 8d showed the greatest protective activities against TMV and TSWV, with the EC50 values of 128.5 and 236.8 μg mL–1, respectively, which were superior to those of ningnanmycin (238.5 and 315.7 μg mL–1, respectively). Moreover, compound 8d could significantly improve the defense enzyme activities of peroxidase, chitinase, and β-1,3-glucanase. Proteomic and transcriptome analyses indicated that compound 8d regulated gene transcription and protein expression levels involved in the defense response to resist virus infection. The present study revealed that compound 8d is a potential lead candidate for the development of novel, eco-friendly, and natural-product-based antiviral agents.
研究领域:
植物学
·
病毒学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2020
·
IF 4.236
Hu Ao,Li Jing,Tang Wei,Liu Ge,Zhang Haiwei,Liu Chunlan,Chen Xulin
Influenza virus RNA-dependent RNA polymerase (vRdRp) does not have capping activity and relies on the capped RNAs produced by the host RNA polymerase II (RNAPII). The viral polymerases process the capped RNAs to produce short capped RNA fragments that are used as primers to initiate the transcription of viral mRNAs. This process, known as cap-snatching, can be targeted by antiviral therapeutics. Here, anthralin was identified as an inhibitor against influenza a virus (IAV) infection by targeting the cap-snatching activity of the viral polymerase. Anthralin, an FDA-approved drug used in the treatment of psoriasis, shows antiviral activity against IAV infection in vitro and in vivo. Importantly, anthralin significantly reduces weight loss, lung injury, and mortality caused by IAV infection in mice. The mechanism of action study revealed that anthralin inhibits the cap-binding function of PB2 subunit and endonuclease activity of PA. As a result, viral mRNA transcription is blocked, leading to the decreases in viral RNA replication and viral protein expression. In conclusion, anthralin has been demonstrated to have the potential of an alternative antiviral against influenza virus infection. Also, targeting the captive pocket structure that includes the N-terminus of PA endonuclease domain and the C-terminal of PB2 cap-binding domain of IAV RdRp may be an excellent strategy for developing anti-influenza drugs.
研究领域:
病毒学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）