scholarly journals Broad Antiviral Activity of Ginkgolic Acid against Chikungunya, Mayaro, Una, and Zika Viruses

Viruses ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 449 ◽  
Author(s):  
Dalkiria Campos ◽  
Susana Navarro ◽  
Yessica Yadira Llamas-González ◽  
Madelaine Sugasti ◽  
José González-Santamaría
Keyword(s):  
Antiviral Activity ◽  
Protein Expression ◽  
Viral Protein ◽  
Biological Activities ◽  
Virucidal Activity ◽  
Ginkgolic Acid ◽  
Viral Protein Expression ◽  
Viral Progeny ◽  
Dose Dependent Decrease ◽  
Dose Dependent

The alphaviruses Chikungunya (CHIKV), Mayaro (MAYV), Una (UNAV), and the flavivirus Zika (ZIKV) are emerging or re-emerging arboviruses which are responsible for frequent epidemic outbreaks. Despite the large impact of these arboviruses on health systems, there are no approved vaccines or treatments to fight these infections. As a consequence, there is an urgent need to discover new antiviral drugs. Natural products are a rich source of compounds with distinct biological activities, including antiviral properties. Thus, we aimed to explore the potential antiviral activity of Ginkgolic acid against the arboviruses CHIKV, MAYV, UNAV, and ZIKV. Viral progeny production in supernatants from cells treated or not treated with Ginkgolic acid was quantified by plaque-forming assay. Ginkgolic acid’s direct virucidal activity against these arboviruses was also determined. Additionally, viral protein expression was assessed using Western blot and immunofluorescence. Our results reveal that Ginkgolic acid promotes a dose-dependent decrease in viral titers in all tested viruses. Moreover, the compound demonstrated strong virucidal activity. Finally, we found that viral protein expression was affected by treatment with this drug. Collectively, these findings suggest that Ginkgolic acid could have broader antiviral activity.

scholarly journals HSV-2 glycoprotein J promotes viral protein expression and virus spread

Virology ◽  
2018 ◽  
Vol 525 ◽  
pp. 83-95 ◽  
Author(s):  
Yalan Liu ◽  
Xinmeng Guan ◽  
Chuntian Li ◽  
Fengfeng Ni ◽  
Sukun Luo ◽  
...  
Keyword(s):  
Protein Expression ◽  
Viral Protein ◽  
Virus Spread ◽  
Viral Protein Expression

scholarly journals Mammalian orthoreovirus Infection is Enhanced in Cells Pre-Treated with Sodium Arsenite

Viruses ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 563 ◽  
Author(s):  
Michael M. Lutz ◽  
Megan P. Worth ◽  
Meleana M. Hinchman ◽  
John S.L. Parker ◽  
Emily D. Ledgerwood
Keyword(s):  
Protein Expression ◽  
Stress Responses ◽  
Viral Protein ◽  
Sodium Arsenite ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Viral Protein Expression ◽  
Viral Yield ◽  
Pre Treatment ◽  
In Cells

Following reovirus infection, cells activate stress responses that repress canonical translation as a mechanism to limit progeny virion production. Work by others suggests that these stress responses, which are part of the integrated stress response (ISR), may benefit rather than repress reovirus replication. Here, we report that compared to untreated cells, treating cells with sodium arsenite (SA) to activate the ISR prior to infection enhanced viral protein expression, percent infectivity, and viral titer. SA-mediated enhancement was not strain-specific, but was cell-type specific. While SA pre-treatment of cells offered the greatest enhancement, treatment within the first 4 h of infection increased the percent of cells infected. SA activates the heme-regulated eIF2α (HRI) kinase, which phosphorylates eukaryotic translation initiation factor 2 alpha (eIF2α) to induce stress granule (SG) formation. Heat shock (HS), another activator of HRI, also induced eIF2α phosphorylation and SGs in cells. However, HS had no effect on percent infectivity or viral yield but did enhance viral protein expression. These data suggest that SA pre-treatment perturbs the cell in a way that is beneficial for reovirus and that this enhancement is independent of SG induction. Understanding how to manipulate the cellular stress responses during infection to enhance replication could help to maximize the oncolytic potential of reovirus.

scholarly journals Characterization and cardiovascular actions of endothelin-1 and endothelin-3 from the American alligator

2002 ◽  
Vol 282 (2) ◽  
pp. R594-R602 ◽  
Author(s):  
Björn Platzack ◽  
Yuqi Wang ◽  
Dane Crossley ◽  
Valentine Lance ◽  
James W. Hicks ◽  
...  
Keyword(s):  
Blood Flow ◽  
Vascular Resistance ◽  
Biological Activities ◽  
Systemic Blood Pressure ◽  
Second Phase ◽  
Systemic Blood ◽  
Cardiovascular Actions ◽  
Dose Dependent Decrease ◽  
Alligator Mississipiensis ◽  
Dose Dependent

The structures and biological activities of the isoforms of endothelin (ET) in a reptile are unknown. ET-3, whose primary structure is identical to human ET-3 except for the substitution Phe4 → Tyr, and a peptide identical to human ET-1 were isolated from an extract of the lung of the alligator, Alligator mississipiensis. Bolus intravenous injections of alligator ET-3 (10, 30, and 100 pmol/kg) into anesthetized alligators produced dose-dependent decreases in systemic blood pressure (Psys) and systemic vascular resistance (Rsys) without change in heart rate (HR), systemic blood flow (Qsys), pulmonary pressure (Ppul), pulmonary vascular resistance (Rpul), or pulmonary blood flow (Qpul). At a dose of 300 pmol/kg, the initial vasodilatation was followed by an increase in Rsys and decreases in Qsys and Ppul. The response to intravenous human/alligator ET-1 (10, 30, 100, and 300 pmol/kg) was biphasic at all doses with initial decreases in Psys and Rsys being followed by sustained increases in these parameters. In the pulmonary circulation, ET-1 produced a dose-dependent decrease in Qpul and an increase in Rpul during the first phase of the response but no significant change during the second phase. There was no change in HR in response to ET-1. The vasodilatator action of arginine, but not ET-1, was attenuated by N ω-nitro-l-arginine methyl ester, indicating that the effect of the peptide is probably not mediated through increased synthesis of nitric oxide. The data demonstrate that the structure of the ET isoforms has been strongly conserved during the evolution of vertebrates but that cardiovascular actions differ significantly between the alligator and mammals, especially in the magnitude and duration of the hypotensive response.

scholarly journals Pervasive Transcription of a Herpesvirus Genome Generates Functionally Important RNAs

mBio ◽  
2014 ◽  
Vol 5 (2) ◽  
Author(s):  
Susan P. Canny ◽  
Tiffany A. Reese ◽  
L. Steven Johnson ◽  
Xin Zhang ◽  
Amal Kambal ◽  
...  
Keyword(s):  
Life Cycle ◽  
Protein Expression ◽  
Viral Protein ◽  
Viral Life Cycle ◽  
Murine Cytomegalovirus ◽  
Functional Importance ◽  
Viral Protein Expression ◽  
Novel Transcripts ◽  
Herpesvirus Genome ◽  
Pervasive Transcription

ABSTRACTPervasive transcription is observed in a wide range of organisms, including humans, mice, and viruses, but the functional significance of the resulting transcripts remains uncertain. Current genetic approaches are often limited by their emphasis on protein-coding open reading frames (ORFs). We previously identified extensive pervasive transcription from the murine gammaherpesvirus 68 (MHV68) genome outside known ORFs and antisense to known genes (termed expressed genomic regions [EGRs]). Similar antisense transcripts have been identified in many other herpesviruses, including Kaposi’s sarcoma-associated herpesvirus and human and murine cytomegalovirus. Despite their prevalence, whether these RNAs have any functional importance in the viral life cycle is unknown, and one interpretation is that these are merely “noise” generated by functionally unimportant transcriptional events. To determine whether pervasive transcription of a herpesvirus genome generates RNA molecules that are functionally important, we used a strand-specific functional approach to target transcripts from thirteen EGRs in MHV68. We found that targeting transcripts from six EGRs reduced viral protein expression, proving that pervasive transcription can generate functionally important RNAs. We characterized transcripts emanating from EGRs 26 and 27 in detail using several methods, including RNA sequencing, and identified several novel polyadenylated transcripts that were enriched in the nuclei of infected cells. These data provide the first evidence of the functional importance of regions of pervasive transcription emanating from MHV68 EGRs. Therefore, studies utilizing mutation of a herpesvirus genome must account for possible effects on RNAs generated by pervasive transcription.IMPORTANCEThe fact that pervasive transcription produces functionally important RNAs has profound implications for design and interpretation of genetic studies in herpesviruses, since such studies often involve mutating both strands of the genome. This is a common potential problem; for example, a conservative estimate is that there are an additional 73,000 nucleotides transcribed antisense to annotated ORFs from the 119,450-bp MHV68 genome. Recognizing the importance of considering the function of each strand of the viral genome independently, we used strand-specific approaches to identify six regions of the genome encoding transcripts that promoted viral protein expression. For two of these regions, we mapped novel transcripts and determined that targeting transcripts from these regions reduced viral replication and the expression of other viral genes. This is the first description of a function for these RNAs and suggests that novel transcripts emanating from regions of pervasive transcription are critical for the viral life cycle.

scholarly journals Adaptation of an H7N7 equine influenza A virus in mice

2007 ◽  
Vol 88 (2) ◽  
pp. 547-553 ◽  
Author(s):  
Kyoko Shinya ◽  
Shinji Watanabe ◽  
Toshihiro Ito ◽  
Noriyuki Kasai ◽  
Yoshihiro Kawaoka
Keyword(s):  
Protein Expression ◽  
Influenza A Virus ◽  
Virus Replication ◽  
Viral Protein ◽  
Influenza A ◽  
Animal Species ◽  
Influenza A Viruses ◽  
Equine Influenza ◽  
Viral Protein Expression ◽  
Wild Waterfowl

Wild waterfowl are a reservoir for influenza A viruses, which can be transmitted from these birds to other animal species. Occasionally, influenza A viruses are transmitted to other animal species from animals other than wild waterfowl, e.g. an equine influenza virus has been transmitted to dogs and caused outbreaks. To understand the molecular mechanism by which influenza A viruses adapt to a new animal species, the molecular changes involved in the adaptation of an H7N7 equine influenza A virus were studied in mice. Mutations in the mouse-adapted virus mapped to one amino acid change in the PA protein, one in PB2 and two in PB1. Of these mutations, the Glu-to-Lys substitution at position 627 of PB2 (PB2-E627K) increased virulence appreciably. To understand the mechanism of this increased virulence, a recombinant virus expressing a reporter green fluorescent protein was constructed, thus enabling the effect of this mutation on viral protein expression to be tested in the context of virus replication in situ. It was found that the PB2-E627K substitution in this equine virus contributed to increased viral protein expression and virus replication in mouse cells and enhanced brain invasiveness in mice. These results demonstrate that the importance of the PB2-E627K substitution for mouse adaptation, which was identified previously in human H5N1 isolates, extends to equine influenza A virus.

scholarly journals Antiviral Activity of Kagocel® on the Model of Experimental Lethal Influenza Infection

2020 ◽  
Vol 65 (1-2) ◽  
pp. 15-20
Author(s):  
V. V. Zarubaev ◽  
A. V. Garshinina ◽  
A. V. Slita ◽  
S. V. Belyaevskaya ◽  
I. N. Lavrentieva
Keyword(s):  
Antiviral Activity ◽  
Influenza Infection ◽  
High Morbidity ◽  
Interferon Inducer ◽  
Reference Drug ◽  
Specific Mortality ◽  
Influenza Pneumonia ◽  
Prophylactic Use ◽  
Dose Dependent Decrease ◽  
Dose Dependent

Despite the obvious advances in vaccination and therapy, influenza remains a poorly controlled infection with high morbidity and mortality. This study examined the antiviral activity of interferon inducer Kagocel on a mouse model of lethal influenza pneumonia. It has been shown that the therapeutic and prophylactic use of Kagocel leads to a dose-dependent decrease in specific mortality and suppression of virus reproduction in lung tissue. The effect of Kagocel was statistically identical to the effect of the reference drug — Arbidol (umifenovir).

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