scholarly journals Nitrogen-Based Heterocyclic Compounds: A Promising Class of Antiviral Agents against Chikungunya Virus

Life ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 16
Author(s):  
Andreza C. Santana ◽  
Ronaldo C. Silva Filho ◽  
José C. J. M. D. S. Menezes ◽  
Diego Allonso ◽  
Vinícius R. Campos
Keyword(s):  
Antiviral Activity ◽  
Mechanism Of Action ◽  
Heterocyclic Compounds ◽  
Chikungunya Virus ◽  
Antiviral Agents ◽  
Antiviral Drug ◽  
Important Class ◽  
Available Nitrogen ◽  
Global Threat ◽  
Present Understanding

Arboviruses, in general, are a global threat due to their morbidity and mortality, which results in an important social and economic impact. Chikungunya virus (CHIKV), one of the most relevant arbovirus currently known, is a re-emergent virus that causes a disease named chikungunya fever, characterized by a severe arthralgia (joint pains) that can persist for several months or years in some individuals. Until now, no vaccine or specific antiviral drug is commercially available. Nitrogen heterocyclic scaffolds are found in medications, such as aristeromycin, favipiravir, fluorouracil, 6-azauridine, thioguanine, pyrimethamine, among others. New families of natural and synthetic nitrogen analogous compounds are reported to have significant anti-CHIKV effects. In the present work, we focus on these nitrogen-based heterocyclic compounds as an important class with CHIKV antiviral activity. We summarize the present understanding on this class of compounds against CHIKV and also present their possible mechanism of action.

scholarly journals Evaluation of Antiviral Activities of Curcumin Derivatives against HSV-1 in Vero Cell Line

2010 ◽  
Vol 5 (12) ◽  
pp. 1934578X1000501 ◽  
Author(s):  
Keivan Zandi ◽  
Elissa Ramedani ◽  
Khosro Mohammadi ◽  
Saeed Tajbakhsh ◽  
Iman Deilami ◽  
...  
Keyword(s):  
Cell Culture ◽  
Antiviral Activity ◽  
Vero Cell ◽  
Cell Line ◽  
Antiviral Agents ◽  
Antiviral Drug ◽  
In Vitro Study ◽  
Vero Cell Line ◽  
Hsv 1

Antiviral drug resistance is one of the most common problems in medicine, and, therefore, finding new antiviral agents, especially from natural resources, seems to be necessary. This study was designed to assay the antiviral activity of curcumin and its new derivatives like gallium-curcumin and Cu-curcumin on replication of HSV-1 in cell culture. The research was performed as an in vitro study in which the antiviral activity of different concentrations of three substances including curcumin, Gallium-curcumin and Cu-curcumin were tested on HSV-1. The cytotoxicity of the tested compounds was also evaluated on the Vero cell line. The CC50 values for curcumin, gallium-curcumin and Cu-curcumin were 484.2 μg/mL, 255.8 μg/mL and 326.6 μg/mL, respectively, and the respective IC50 values 33.0 μg/mL, 13.9 μg/mL and 23.1 μg/mL. The calculated SI values were 14.6, 18.4 and 14.1, respectively. The results showed that curcumin and its new derivatives have remarkable antiviral effects on HSV-1 in cell culture.

scholarly journals Structural and functional basis for pan-CoV fusion inhibitors against SARS-CoV-2 and its variants with preclinical evaluation

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Shuai Xia ◽  
Qiaoshuai Lan ◽  
Yun Zhu ◽  
Chao Wang ◽  
Wei Xu ◽  
...  
Keyword(s):  
Public Health ◽  
Antiviral Activity ◽  
South African ◽  
Antiviral Agents ◽  
Clinical Development ◽  
Nasal Administration ◽  
S Protein ◽  
Preclinical Evaluation ◽  
Fusion Inhibitors ◽  
Global Threat

AbstractThe COVID-19 pandemic poses a global threat to public health and economy. The continuously emerging SARS-CoV-2 variants present a major challenge to the development of antiviral agents and vaccines. In this study, we identified that EK1 and cholesterol-coupled derivative of EK1, EK1C4, as pan-CoV fusion inhibitors, exhibit potent antiviral activity against SARS-CoV-2 infection in both lung- and intestine-derived cell lines (Calu-3 and Caco2, respectively). They are also effective against infection of pseudotyped SARS-CoV-2 variants B.1.1.7 (Alpha) and B.1.1.248 (Gamma) as well as those with mutations in S protein, including N417T, E484K, N501Y, and D614G, which are common in South African and Brazilian variants. Crystal structure revealed that EK1 targets the HR1 domain in the SARS-CoV-2 S protein to block virus-cell fusion and provide mechanistic insights into its broad and effective antiviral activity. Nasal administration of EK1 peptides to hACE2 transgenic mice significantly reduced viral titers in lung and intestinal tissues. EK1 showed good safety profiles in various animal models, supporting further clinical development of EK1-based pan-CoV fusion inhibitors against SARS-CoV-2 and its variants.

scholarly journals Characterization of β-d-N4-Hydroxycytidine as a Novel Inhibitor of Chikungunya Virus

2017 ◽  
Vol 61 (4) ◽  
Author(s):  
Maryam Ehteshami ◽  
Sijia Tao ◽  
Keivan Zandi ◽  
Hui-Mien Hsiao ◽  
Yong Jiang ◽  
...  
Keyword(s):  
Cell Culture ◽  
Human Health ◽  
Chikungunya Virus ◽  
Antiviral Agents ◽  
Scientific Interest ◽  
The Caribbean ◽  
Global Threat

ABSTRACT Chikungunya virus (CHIKV) represents a reemerging global threat to human health. Recent outbreaks across Asia, Europe, Africa, and the Caribbean have prompted renewed scientific interest in this mosquito-borne alphavirus. There are currently no vaccines against CHIKV, and treatment has been limited to nonspecific antiviral agents, with suboptimal outcomes. Herein, we have identified β-d-N 4-hydroxycytidine (NHC) as a novel inhibitor of CHIKV. NHC behaves as a pyrimidine ribonucleoside and selectively inhibits CHIKV replication in cell culture.

scholarly journals Synthesis and Antiviral Activity of Camphene Derivatives against Different Types of Viruses

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2235
Author(s):  
Anastasiya S. Sokolova ◽  
Valentina P. Putilova ◽  
Olga I. Yarovaya ◽  
Anastasiya V. Zybkina ◽  
Ekaterina D. Mordvinova ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Antiviral Activity ◽  
Rational Design ◽  
Ebola Virus ◽  
Viral Infections ◽  
Antiviral Agents ◽  
Antiviral Drug ◽  
Surface Proteins ◽  
Hantaan Virus

To date, the ‘one bug-one drug’ approach to antiviral drug development cannot effectively respond to the constant threat posed by an increasing diversity of viruses causing outbreaks of viral infections that turn out to be pathogenic for humans. Evidently, there is an urgent need for new strategies to develop efficient antiviral agents with broad-spectrum activities. In this paper, we identified camphene derivatives that showed broad antiviral activities in vitro against a panel of enveloped pathogenic viruses, including influenza virus A/PR/8/34 (H1N1), Ebola virus (EBOV), and the Hantaan virus. The lead-compound 2a, with pyrrolidine cycle in its structure, displayed antiviral activity against influenza virus (IC50 = 45.3 µM), Ebola pseudotype viruses (IC50 = 0.12 µM), and authentic EBOV (IC50 = 18.3 µM), as well as against pseudoviruses with Hantaan virus Gn-Gc glycoprotein (IC50 = 9.1 µM). The results of antiviral activity studies using pseudotype viruses and molecular modeling suggest that surface proteins of the viruses required for the fusion process between viral and cellular membranes are the likely target of compound 2a. The key structural fragments responsible for efficient binding are the bicyclic natural framework and the nitrogen atom. These data encourage us to conduct further investigations using bicyclic monoterpenoids as a scaffold for the rational design of membrane-fusion targeting inhibitors.

scholarly journals Antiviral activity of silymarin and baicalein against dengue virus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhao Xuan Low ◽  
Brian Ming OuYong ◽  
Pouya Hassandarvish ◽  
Chit Laa Poh ◽  
Babu Ramanathan
Keyword(s):  
Antiviral Activity ◽  
Dengue Virus ◽  
Viral Entry ◽  
Dengue Infection ◽  
Antiviral Agents ◽  
Antiviral Drug ◽  
Vero Cells ◽  
Viral Envelope ◽  
E Protein

AbstractDengue is an arthropod-borne viral disease that has become endemic and a global threat in many countries with no effective antiviral drug available currently. This study showed that flavonoids: silymarin and baicalein could inhibit the dengue virus in vitro and were well tolerated in Vero cells with a half-maximum cytotoxic concentration (CC50) of 749.70 µg/mL and 271.03 µg/mL, respectively. Silymarin and baicalein exerted virucidal effects against DENV-3, with a selective index (SI) of 10.87 and 21.34, respectively. Baicalein showed a better inhibition of intracellular DENV-3 progeny with a SI of 7.82 compared to silymarin. Baicalein effectively blocked DENV-3 attachment (95.59%) to the Vero cells, while silymarin prevented the viral entry (72.46%) into the cells, thus reducing viral infectivity. Both flavonoids showed promising antiviral activity against all four dengue serotypes. The in silico molecular docking showed that silymarin could bind to the viral envelope (E) protein with a binding affinity of − 8.5 kcal/mol and form hydrogen bonds with the amino acids GLN120, TRP229, ASN89, and THR223 of the E protein. Overall, this study showed that silymarin and baicalein exhibited potential anti-DENV activity and could serve as promising antiviral agents for further development against dengue infection.

Pharmacologic Considerations for Antiviral Drug Development

1996 ◽  
Vol 30 (9) ◽  
pp. 972-977 ◽  
Author(s):  
Courtney V Fletcher
Keyword(s):  
Drug Development ◽  
Mechanism Of Action ◽  
Rapid Development ◽  
Antiviral Agents ◽  
Antiviral Drug ◽  
Antiviral Agent ◽  
Inoculum Size ◽  
Kidney Transplant Recipients ◽  
Therapeutic Success ◽  
Early Integration

OBJECTIVE: To discuss pharmacologic considerations for the development of antiviral agents. DATA SOURCES: English-language literature pertaining to the development and clinical evaluation of antiviral compounds, primarily agents targeted against herpes group viruses and HIV. STUDY SELECTION AND DATA EXTRACTION: Pertinent information, as judged by the author, was selected for discussion. DATA SYNTHESIS: Drug development of antiviral agents presents unique problems compared with that of antimicrobial and other agents. Understanding the mechanism of action and both pharmacokinetic and pharmacodynamic considerations is critical to developing a rational dosing strategy and safe, effective use. The lack of standardized methods for antiviral susceptibility testing and the influence of factors such as strain of virus, host cell type, culture medium, inoculum size, end point, and method of measurement on the results obtained illustrate factors that complicate preclinical pharmacologic analysis of antiviral agents. Acyclovir offers a model for clinical drug development. Its mechanism of action, pharmacokinetics, and pharmacodynamics have been studied extensively. Rational guidelines for usage are available, including guidelines in special patient populations such as kidney transplant recipients and neonates. A pregnancy registry has allowed evaluation of the incidence of birth defects in fetuses exposed to systemic acyclovir. Several pitfalls in antiviral drug development are associated with inadequate pharmacologic information. The development of dextran sulfate and fialuridine provides two examples. Integration of pharmacokinetic and pharmacodynamic analyses using modern sampling and analysis techniques may facilitate more rapid development of antiviral agents and more informed dosage regimens to achieve the highest probability of therapeutic success. CONCLUSIONS: Insufficient knowledge of the pharmacokinetic and pharmacodynamic characteristics of an antiviral agent is a barrier to efficient drug development. Application and early integration of pharmacologic information into clinical investigations hold promise as a means to shorten the development process and, more importantly, to arrive at informative dosing regimens that optimize therapeutic success.

scholarly journals In Vitro and in Vivo Antiviral Activity of Mizoribine Against Foot-And-Mouth Disease Virus

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1723 ◽  
Author(s):  
Shi-Fang Li ◽  
Mei-Jiao Gong ◽  
Yue-Feng Sun ◽  
Jun-Jun Shao ◽  
Yong-Guang Zhang ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Early Stage ◽  
Antiviral Agents ◽  
Antiviral Drug ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Mouth Disease Virus ◽  
Foot And Mouth

Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-hoofed animals, which has significant economic consequences in affected countries. As the currently available vaccines against FMD provide no protection until 4–7 days post-vaccination, the only alternative method to control the spread of FMD virus (FMDV) during outbreaks is the application of antiviral agents. Hence, it is important to identify effective antiviral agents against FMDV infection. In this study, we found that mizoribine has potent antiviral activity against FMDV replication in IBRS-2 cells. A time-of-drug-addition assay demonstrated that mizoribine functions at the early stage of replication. Moreover, mizoribine also showed antiviral effect on FMDV in vivo. In summary, these results revealed that mizoribine could be a potential antiviral drug against FMDV.

scholarly journals Inhibition of Enterovirus 71 by Picochlorum sp. 122 via AKT and ATM/ATR Signaling Pathways

2021 ◽  
Author(s):  
Min Guo ◽  
Ruilin Zheng ◽  
Hua-lian Wu ◽  
Danyang Chen ◽  
Jingyao Su ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Signaling Pathways ◽  
Antiviral Agents ◽  
Antiviral Drug ◽  
Enterovirus 71 ◽  
Foot And Mouth Disease ◽  
Vero Cells ◽  
Host Cells ◽  
Global Public Health ◽  
Protein Levels

Abstract Enterovirus 71 (EV71) pose a critical threat in global public health and may lead to severe and even lethal cases of hand-foot-and-mouth disease (HFMD). No effective antiviral agents are available to the masses for treatment of HFMD caused by EV71. Polysaccharide provides a good clinical application for antivirus. Polysaccharides extracted from Picochlorum sp. 122 (PPE) is a kind of seaweed Polysaccharides, the reports on its antiviral activity are limited. In this study, the antiviral activity was verified in Vero cells. Briefly, PPE has been demonstrated to restrain EV71 infection through MTT assay and cellular cytopathic effect. In addition, the decrease of the nucleic acid and protein levels of VP1 indicated PPE effectively inhibited the proliferation of EV71 in Vero cells. Furthermore, the annexinV-affinity assay suggested that PPE protected host cells from apoptosis. The mechanistic investigations revealed that PPE restrained EV71-induced host-cells apoptosis by AKT and ATM/ATR signaling pathways. In conclusion, these results demonstrate PPE is a hopeful antiviral drug for the infection of EV71.

scholarly journals Screening for antiviral activity of two purified saponin fractions of Quillaja spp. against Yellow Fever Virus and Chikungunya Virus

2020 ◽  
Vol 8 (9) ◽  
pp. 205-214
Author(s):  
Eduardo Troian ◽  
Karoline Schallenberger ◽  
Francini Da Silva ◽  
Gabriela Dietrich ◽  
Fernando Ferreira Chiesa ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Yellow Fever ◽  
Chikungunya Virus ◽  
Yellow Fever Virus ◽  
Antiviral Drug ◽  
Fever Virus ◽  
African Green Monkey Kidney ◽  
Plaque Reduction Assay ◽  
Enveloped Virus

Yellow Fever Virus (YFV) and Chikungunya Virus (CHIV) are neglected reemerging pathogens that cause comorbidities worldwide. Since no antiviral drug is prescribed for those infections, there is a demand on researching compounds that inhibit viral replication. Saponins are amphiphilic compounds that already demonstrated in vitro activity against enveloped virus. Therefore, two purified saponin fractions from Quillaja spp. were evaluated regarding their antiviral potential against YFV and CHIKV. The cell line used in this study was VERO (African green monkey kidney cells) since it is permissive to the replication of both viruses. The antiviral activity of both saponins fractions was screened using the plaque reduction assay protocol. Although saponins did not inhibited YFV replication, they strongly inhibited CHIKV. To confirm the absence of antiviral activity of Quillaja saponins against YFV, the cytopathic effect inhibition assay was performed also. Further studies are required to determine the antiviral mechanisms involved in the CHIKV inhibition.

scholarly journals Synthesis and Anti-Chikungunya Virus (CHIKV) Activity of Novel 1,4-Naphthoquinone Sulfonamide and Sulfonate Ester Derivatives

2022 ◽  
Author(s):  
Paulo Pacheco ◽  
Daniel Gonzaga ◽  
Cláudio Cirne-Santos ◽  
Caroline Barros ◽  
Max Gomes ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Pharmacological Treatment ◽  
Drug Targets ◽  
Chikungunya Virus ◽  
Antiviral Drug ◽  
Sulfonate Group ◽  
In Silico Studies ◽  
Virucidal Effect ◽  
Toxic Potential ◽  
Sulfonate Ester

Chikungunya virus (CHIKV) is a re-emerging disease caused by an alphavirus of the Togaviridae family. Since its first description in 1952, the disease has spread worldwide, affecting populations in both tropical and temperate countries. To date, there is no licensed vaccine or specific pharmacological treatment. Therefore, there is an increasing urgency in developing new antiviral drugs capable of specifically inhibiting viral replication. In the present work, we report the synthesis and antiviral activity evaluation of nineteen naphthoquinone derivatives, containing a sulfonamide or sulfonate group. Cell viability assays indicated a low toxic potential for all tested compounds and inhibitory assays against CHIKV identified five compounds with potent activity. The compounds were also evaluated for their virucidal potential, and the results demonstrated that compound 11a exhibited a virucidal effect higher than 70% in the treatment with 20 µM. Furthermore, in silico studies were performed to predict the antiviral drug targets.

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