scholarly journals [6]-Gingerol Inhibits Chikungunya Virus Infection by Suppressing Viral Replication

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Rahma F. Hayati ◽  
Cynthia D. Better ◽  
Dionisius Denis ◽  
Amalina G. Komarudin ◽  
Anom Bowolaksono ◽  
...  

Chikungunya (CHIK) is a reemerging arboviral disease caused by chikungunya virus (CHIKV) infection. The disease is clinically hallmarked by prolonged debilitating joint pain. Currently, there is no specific antiviral medication nor commercial vaccine available for treatment of the disease, which makes the discovery or development of specific anti-CHIKV compounds a priority. Ginger (Zingiber officinale Roscoe) is widely known for its various health benefits. The compound [6]-gingerol is the main active ingredient found in ginger. This study sought to determine the potential of [6]-gingerol antiviral activity against CHIKV infection using in vitro human hepatocyte HepG2 cells. The antiviral activity mechanism was investigated using direct virucidal and four indirect (pre-, post-, full-, and prevention) treatment assays. [6]-Gingerol showed weak virucidal activity but significant indirect antiviral activity against CHIKV through post- and full treatment with I C 50 of 0.038 mM and 0.031 mM, respectively, without showing cell cytotoxicity. The results indicated that [6]-gingerol inhibits CHIKV infection through suppression of viral replication. Together, this study confirms the potential use of [6]-gingerol for CHIK antiviral compound.

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Poonam Patil ◽  
Megha Agrawal ◽  
Shahdab Almelkar ◽  
Manish Kumar Jeengar ◽  
Ashwini More ◽  
...  

Abstract Background Chikungunya virus (CHIKV), a serious health problem in several tropical countries, is the causative agent of chikungunya fever. Approved antiviral therapies or vaccines for the treatment or prevention of CHIKV infections are not available. As diverse natural phenolic compounds have been shown to possess antiviral activities, we explored the antiviral activity of α-Mangostin, a xanthanoid, against CHIKV infection. Methods The in vitro prophylactic and therapeutic effects of α-Mangostin on CHIKV replication in Vero E6 cells were investigated by administering it under pre, post and cotreatment conditions. The antiviral activity was determined by foci forming unit assay, quantitative RT-PCR and cell-based immune-fluorescence assay. The molecular mechanism of inhibitory action was further proposed using in silico molecular docking studies. Results In vitro studies revealed that 8 µM α-Mangostin completely inhibited CHIKV infectivity under the cotreatment condition. CHIKV replication was also inhibited in virus-infected mice. This is the first in vivo study which clearly showed that α-Mangostin is effective in vivo by significantly reducing virus replication in serum and muscles. Molecular docking indicated that α-Mangostin can efficiently interact with the E2–E1 heterodimeric glycoprotein and the ADP-ribose binding cavity of the nsP3 macrodomain. Conclusions The findings suggest that α-Mangostin can inhibit CHIKV infection and replication through possible interaction with multiple CHIKV target proteins and might act as a prophylactic/therapeutic agent against CHIKV.


Agronomy ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 320
Author(s):  
Nisar Ahmad Zahid ◽  
Hawa Z.E. Jaafar ◽  
Mansor Hakiman

Ginger (Zingiber officinale Roscoe) var. Bentong is a monocotyledon plant that belongs to the Zingiberaceae family. Bentong ginger is the most popular cultivar of ginger in Malaysia, which is conventionally propagated by its rhizome. As its rhizomes are the economic part of the plant, the allocation of a large amount of rhizomes as planting materials increases agricultural input cost. Simultaneously, the rhizomes’ availability as planting materials is restricted due to the high demand for fresh rhizomes in the market. Moreover, ginger propagation using its rhizome is accompanied by several types of soil-borne diseases. Plant tissue culture techniques have been applied to produce disease-free planting materials of ginger to overcome these problems. Hence, the in vitro-induced microrhizomes are considered as alternative disease-free planting materials for ginger cultivation. On the other hand, Bentong ginger has not been studied for its microrhizome induction. Therefore, this study was conducted to optimize sucrose and plant growth regulators (PGRs) for its microrhizome induction. Microrhizomes were successfully induced in Murashige and Skoog (MS) medium supplemented with a high sucrose concentration (>45 g L−1). In addition, zeatin at 5–10 µM was found more effective for microrhizome induction than 6-benzylaminopurine (BAP) at a similar concentration. The addition of 7.5 µM 1-naphthaleneacetic acid (NAA) further enhanced microrhizome formation and reduced sucrose’s required dose that needs to be supplied for efficient microrhizome formation. MS medium supplemented with 60 g L−1 sucrose, 10 µM zeatin and 7.5 µM NAA was the optimum combination for the microrhizome induction of Bentong ginger. The in vitro-induced microrhizomes sprouted indoors in moist sand and all the sprouted microrhizomes were successfully established in field conditions. In conclusion, in vitro microrhizomes can be used as disease-free planting materials for the commercial cultivation of Bentong ginger.


2021 ◽  
Vol 9 (2) ◽  
pp. 307
Author(s):  
Evelyn J. Franco ◽  
Xun Tao ◽  
Kaley C. Hanrahan ◽  
Jieqiang Zhou ◽  
Jürgen B. Bulitta ◽  
...  

Chikungunya virus (CHIKV) is an alphavirus associated with a broad tissue tropism for which no antivirals or vaccines are approved. This study evaluated the antiviral potential of favipiravir (FAV), interferon-alpha (IFN), and ribavirin (RBV) against CHIKV as mono- and combination-therapy in cell lines that are clinically relevant to human infection. Cells derived from human connective tissue (HT-1080), neurons (SK-N-MC), and skin (HFF-1) were infected with CHIKV and treated with different concentrations of FAV, IFN, or RBV. Viral supernatant was sampled daily and the burden was quantified by plaque assay on Vero cells. FAV and IFN were the most effective against CHIKV on various cell lines, suppressing the viral burden at clinically achievable concentrations; although the degree of antiviral activity was heavily influenced by cell type. RBV was not effective and demonstrated substantial toxicity, indicating that it is not a feasible candidate for CHIKV. The combination of FAV and IFN was then assessed on all cell lines. Combination therapy enhanced antiviral activity in HT-1080 and SK-N-MC cells, but not in HFF-1 cells. We developed a pharmacokinetic/pharmacodynamic model that described the viral burden and inhibitory antiviral effect. Simulations from this model predicted clinically relevant concentrations of FAV plus IFN completely suppressed CHIKV replication in HT-1080 cells, and considerably slowed down the rate of viral replication in SK-N-MC cells. The model predicted substantial inhibition of viral replication by clinical IFN regimens in HFF-1 cells. Our results highlight the antiviral potential of FAV and IFN combination regimens against CHIKV in clinically relevant cell types.


2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Xianghe Meng ◽  
Darong Yang ◽  
Rong Yu ◽  
Haizhen Zhu

It has been reported that IFN-λs inhibit HCV replication in vitro. But the mechanisms of how IL-28A conducts antiviral activity and the functions of IL-28A-induced ISGs (IFN-stimulated genes) are not fully understood. In this study, we found that IL-28A has the antiviral effect on HCV life cycle including viral replication, assembly, and release. IL-28A and IFN-αsynergistically inhibit virus replication. EPSTI1 (epithelial-stromal interaction 1), one of IL-28A-induced ISGs, plays a vital role in IL-28A-mediated antiviral activity. Furthermore, forced expression of EPSTI1 effectively inhibits HCV replication in the absence of interferon treatment, and knockdown of EPSTI1 contributes to viral enhancement. EPSTI1 can activate PKR promoter and induce several PKR-dependent genes, including IFN-β, IFIT1, OAS1, and RNase L, which is responsible for EPSTI1-mediated antiviral activity.


1997 ◽  
Vol 186 (7) ◽  
pp. 1077-1085 ◽  
Author(s):  
Khalid S.A. Khabar ◽  
Fahad Al-Zoghaibi ◽  
Mohammed N. Al-Ahdal ◽  
Tsugiya Murayama ◽  
Mohammed Dhalla ◽  
...  

Interferon (IFN) exhibits a potent antiviral activity in vitro and plays a major role in the early defense against viruses. Like IFN, the proinflammatory chemokine, interleukin (IL)-8, is induced by viruses and appears in circulation during viral infections. In an in vitro cytopathic effect assay for IFN, we found that IL-8 can inhibit IFN-α activity in a dose-dependent manner. This action was reversed by specific monoclonal antibodies to IL-8. The chemokine was able to attenuate the IFN-mediated inhibition of viral replication as determined by measuring infectious virus yield. IL-8 also diminished the ability of IFN to inhibit an early stage of viral replication since IL-8 attenuated the inhibition of the formation of viral proteins. It appeared that IL-8 interfered with a late rather than an early step of IFN-mediated pathway such as early gene expression. The IL-8 inhibitory action on IFN-α antiviral activity was associated with reduced 2′,5′-A oligoadenylate synthetase activity, a pathway well correlative with the anti– encephalomyocarditis virus action of IFN-α. Understanding pathways that antagonize IFN action may lead to novel approaches to potentiate endogenous and therapeutic IFN.


1998 ◽  
Vol 42 (4) ◽  
pp. 916-920 ◽  
Author(s):  
Q. May Wang ◽  
Robert B. Johnson ◽  
Louis N. Jungheim ◽  
Jeffrey D. Cohen ◽  
Elcira C. Villarreal

ABSTRACT The 2A and 3C proteases encoded by human rhinoviruses (HRVs) are attractive targets for antiviral drug development due to their important roles in viral replication. Homophthalimides were originally identified as inhibitors of rhinovirus 3C protease through our screening effort. Previous studies have indicated that the antiviral activity of certain homophthalimides exceeded their in vitro inhibitory activity against the viral 3C protease, suggesting that an additional mechanism might be involved. Reported here is the identification of homophthalimides as potent inhibitors for another rhinovirus protease, designated 2A. Several homophthalimides exhibit time-dependent inhibition of the 2A protease in the low-micromolar range, and enzyme-inhibitor complexes were identified by mass spectrometry. Compound LY343814, one of the most potent inhibitors against HRV14 2A protease, had an antiviral 50% inhibitory concentration of 4.2 μM in the cell-based assay. Our data reveal that homophthalimides are not only 3C but also 2A protease inhibitors in vitro, implying that the antiviral activity associated with these compounds might result from inactivation of both 2A and 3C proteases in vivo. Since the processing of the viral polyprotein is hierarchical, dual inhibition of the two enzymes may result in cooperative inhibition of viral replication. On the basis of the current understanding of their enzyme inhibitory mechanism, homophthalimides, as a group of novel nonpeptidic antirhinovirus agents, merit further structure-action relationship studies.


2021 ◽  
Author(s):  
Ítalo Fernando da Costa Melo ◽  
João Bosco Batista Nogueira Júnior ◽  
João Paulo Fonseca Tavares

Introdução: Plantas, fungos e bactérias são relatados na literatura como produtores de moléculas oriundas do metabolismo secundário que possuem um vasto leque de atividades biológicas que vão desde atividade antimicrobiana até antitumoral. Em relação as plantas no que diz respeito aos estudos de seus metabólitos secundários/especializados, os óleos essenciais são substâncias naturais ricas em compostos bioativo, sendo os terpenos as moléculas majoritárias nos óleos essenciais, este por sua vez são uma classe de metabólitos que variam de tamanho em função da extensão da cadeia por seus blocos construtores e podendo possuir grupos funcionais que fazem com que a diversidade da atividade biológica seja ainda mais variada. Estes óleos, portanto, possuem potencial para serem usados pela indústria farmacêutica, médica, agronômica entre outras áreas da economia. No que diz respeito ao seu uso dentro da agronomia destaca-se as várias vantagens do uso de óleos essenciais na agricultura, pois são compostos naturais, não deixam resíduos, considerados seguros, de baixo custo e podem ser utilizados pequenas quantidades. Objetivo: Avaliou-se a atividade antifúngica dos óleos essenciais de Zingiber officinale roscoe contra C. cassiicola em condições in vitro. Material e métodos: Nos testes in vitro, foram utilizadas seis concentrações (0,0 µL; 150 µL; 375 µL; 525 µL; 750 µL; 900 µL), com cinco repetições. A determinação antifúngica foi mensurada pela inibição do crescimento micelial, esporulação e germinação. Resultados: As concentrações com maior notoriedade nos resultados foram (750 µL; 900 µL), inibiram 100% o crescimento micelial. Para o ensaio da inibição da esporulação, essas mesmas concentrações obtiveram 100% de inibição. Quanto a inibição da germinação, constatou-se que apenas a concentração de 900 µL, inibiu 100% a germinação de conídios. Conclusão: O óleo essencial obtido do rizoma de Z. officinale roscoe apresentara efeito inibidor significativo do crescimento micelial, esporulação e germinação de Corynespora cassiicola in vitro, indicando um potencial para controle do fungo. Sendo assim estudos posteriores para o desenvolvimento de bioprodutos para o biocontrole do fitopatógeno abre um caminho para o desenvolvimento de uma agricultura mais sustentável.


2020 ◽  
Author(s):  
Sean Ekins ◽  
Peter Madrid

Tilorone demonstrates in vitro antiviral activity against Chikungunya virus (CHIK) and Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV).


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