Antiviral activity of SA-2 against influenza A virus in vitro/vivo and its inhibition of RNA polymerase

Yu, Jie; Wang, Dechuan; Jin, Jing; Xu, Jingying; Li, Mengwei; Wang, Hui; Dou, Jun; Zhou, Changlin

doi:10.1016/j.antiviral.2016.01.011

Cited by 18 publications

(13 citation statements)

References 30 publications

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“…The polymerase complex is a critical component of the viral structure, and inhibition of the polymerase activity reflected the extensive effect of ISG20 on the viral life cycle. Several proteins and compounds inhibit IAV replication by reducing viral polymerase activity [35][36][37]. For instance, the multiple kinase inhibitor WV970 inhibits RNA expression and polymerase activity of IAV and was identified as a novel antiviral drug candidate [36].…”

Section: Discussionmentioning

confidence: 99%

Influenza A Virus-induced expression of ISG20 inhibits viral replication by interacting with nucleoprotein

Yang

et al. 2016

Virus Genes

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Influenza A virus (IAV) is an important pathogen that has a wide range of hosts and represents a threat to the health of humans and several animal species. IAV infection can induce the transcription of many genes in the host. In the present study, we demonstrated for the first time that three different strains of H1N1 IAV induce the expression of an IFN-stimulated gene, ISG20. We determined the antiviral activity of ISG20 against IAV because ISG20 inhibited viral protein expression and reduced the progeny viral titer dependent upon its exonuclease activity. To elucidate the detailed mechanism of ISG20, we further demonstrated that ISG20 impairs the polymerase activity and inhibits both the replication and transcription levels of the M1 and NP genes. Notably, we identified that ISG20 colocalizes and interacts with NP during IAV infection, while exonuclease-inactive mutant ISG20 lacked association with NP, indicating that ISG20 inhibits IAV replication by interacting with NP. Together, these data provide a detailed explanation for the specific antiviral action of ISG20 and suggest that ISG20 may act as a promising antiviral drug candidate against IAV.

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Section: Discussionmentioning

confidence: 99%

Influenza A Virus-induced expression of ISG20 inhibits viral replication by interacting with nucleoprotein

Yang

et al. 2016

Virus Genes

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“…Virus production: The influenza A virus used in this study, containing A/FM/1/47 (H1N1), A/Beijing/32/92 (H3N2) and the H1N1 oseltamivir-resistant mutant strain A/FM/1/47-H275Y (H1N1-H275Y) (by introducing a histidine-to-tyrosine substitution at position 275 into NA [21]), were propagated in 10-day-old embryonated chicken eggs. Viruses were stored at −80 • C.…”

Section: Cells Viruses and Plasmidsmentioning

confidence: 99%

“…The test compounds were synthesized and provided by Dechuan Wang at the Department of Organic Chemistry, China Pharmaceutical University. Its synthesis process was similar to SA-2, which was synthesized according to published procedures [21,23]. The structures and purity of all synthesized compounds were verified by 1H NMR, and the purity was all >95%.…”

Section: Compoundsmentioning

confidence: 99%

Antiviral Activity of Benzoic Acid Derivative NC-5 Against Influenza A Virus and Its Neuraminidase Inhibition

Guo

et al. 2019

IJMS

Self Cite

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The currently available drugs against influenza A virus primarily target neuraminidase (NA) or the matrix protein 2 (M2) ion channel. The emergence of drug-resistant viruses requires the development of new antiviral chemicals. Our study applied a cell-based approach to evaluate the antiviral activity of a series of newly synthesized benzoic acid derivatives, and 4-(2,2-Bis(hydroxymethyl)-5-oxopyrrolidin-l-yl)-3-(5-cyclohexyl-4H-1,2,4-triazol-3-yl)amino). benzoic acid, termed NC-5, was found to possess antiviral activity. NC-5 inhibited influenza A viruses A/FM/1/47 (H1N1), A/Beijing/32/92 (H3N2) and oseltamivir-resistant mutant A/FM/1/47-H275Y (H1N1-H275Y) in a dose-dependent manner. The 50% effective concentrations (EC 50 ) for H1N1 and H1N1-H275Y were 33.6 µM and 32.8 µM, respectively, which showed that NC-5 had a great advantage over oseltamivir in drug-resistant virus infections. The 50% cytotoxic concentration (CC 50 ) of NC-5 was greater than 640 µM. Orally administered NC-5 protected mice infected with H1N1 and H1N1-H275Y, conferring 80% and 60% survival at 100 mg/kg/d, reducing body weight loss, and alleviating virus-induced lung injury. NC-5 could suppress NP and M1 protein expression levels during the late stages of viral biosynthesis and inhibit NA activity, which may influence virus release. Our study proved that NC-5 has potent anti-influenza activity in vivo and in vitro, meaning that it could be regarded as a promising drug candidate to treat infection with influenza viruses, including oseltamivir-resistant viruses.

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“…In the present study, two kinds of CTLs also exhibited obvious virucidal activities against human pathogenic RNA virus (H 1 N 1 ) in vitro. Influenza viruses are highly contagious and cause three to five million cases of severe respiratory illness and approximately 250,000–500,000 deaths annually (Yu et al., ). Our antiviral results suggest that these lectins from the housefly with antiviral activities could be considered a promising drug candidate for the treatment of influenza.…”

Section: Discussionmentioning

confidence: 99%

“…As pattern recognition receptors (PRRs), CTLs were involved in different immune functions including cell adhesion, prophenoloxidase induction, respiratory burst activation, hemocyte nodule formation, phagocytosis, opsonization enhancement, and cellular encapsulation (Wang, Liu, Zhang, Zhao, & Wang, 2012;Yu, Ling, Zhu, Tracy, & Zhu, 2006). These immune functions play prominent roles in nonself recognition and clearance of invading microorganisms (Yu et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Identification and characterization of two novel C‐type lectins from the larvae of housefly, Musca domestica L.

Zhou

Fang

Zheng

et al. 2018

Arch Insect Biochem Physiol

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Lectins and antimicrobial peptides (AMPs) are widely distributed in various insects and play crucial roles in primary host defense against pathogenic microorganisms. Two AMPs (cecropin and attacin) have been identified and characterized in the larvae of housefly. In this study, two novel C-type lectins (CTLs) were obtained from Musca domestica, while their agglutinating and antiviral properties were evaluated. Real-time PCR analysis showed that the mRNA levels of four immune genes (MdCTL1, MdCTL2, Cecropin, and Attacin) from M. domestica were significantly upregulated after injection with killed Gram-negative Escherichia coli. Moreover, purified MdCTL1-2 proteins can agglutinate E. coli and Staphylococcus aureus in the presence of calcium ions, suggesting their immune function is Ca dependent. Sequence analysis indicated that typical WND and QPD motifs were found in the Ca -binding site 2 of carbohydrate recognition domain from MdCTL1-2, which was consistent with their agglutinating activities. Subsequently, antiviral experiments indicated that MdCTL1-2 proteins could significantly reduce the infection rate of Spodoptera frugiperda 9 cells by the baculovirus Autographa californica multicapsid nucleopolyhedrovirus, indicating they might play important roles in insect innate immunity against microbial pathogens. In addition, MdCTL1-2 proteins could effectively inhibit the replication of influenza H N virus, which was similar to the effect of ribavirin. These results suggested that two novel CTLs could be considered a promising drug candidate for the treatment of influenza. Moreover, it is believed that the discovery of the CTLs with antiviral effects in M. domestica will improve our understanding of the molecular mechanism of insect immune response against viruses.

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Antiviral activity of SA-2 against influenza A virus in vitro/vivo and its inhibition of RNA polymerase

Cited by 18 publications

References 30 publications

Influenza A Virus-induced expression of ISG20 inhibits viral replication by interacting with nucleoprotein

Influenza A Virus-induced expression of ISG20 inhibits viral replication by interacting with nucleoprotein

Antiviral Activity of Benzoic Acid Derivative NC-5 Against Influenza A Virus and Its Neuraminidase Inhibition

Identification and characterization of two novel C‐type lectins from the larvae of housefly, Musca domestica L.

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