Review on Dengue Virus Fusion/Entry Process and Their Inhibition by Small Bioactive Molecules

2020 ◽  
Vol 20 ◽  
Author(s):  
Podila Naresh ◽  
Shyam Sunder Pottabatula ◽  
Jubie Selvaraj
Keyword(s):  
Dengue Virus ◽  
Small Molecules ◽  
Conformational Changes ◽  
Yellow Fever Virus ◽  
Antiviral Drug ◽  
Bioactive Molecules ◽  
Fusion Process ◽  
Human Pathogens ◽  
Virus Infections ◽  
E Protein

: Many flavi viruses are noteworthy human pathogens which might be spread by means of mosquitoes and ticks. Despite the availability of vaccines for virus infections such as yellow fever virus, Japanese encephalitic virus, and tickborne encephalitis virus, still flavi virus like dengue is a serious life threatening disease globally. So far, there is no antiviral drug for dengue therapy. In order to address this scientific want, industry and scholarly community have been taking continuos measures to increase the anti flavivirus therapy. In the last two decades, active research is involved in inhibiting the fusion process of the virus entry. In this review, we have comprehensively given the present day expertise of usage of small molecules utilized as fusion inhibitors. We have enumerated the structure, fusion process of dengue virus E protein (DENV E) and amino acids involved during the fusion process. Special emphasis have been given for the small molecules that do conformational changes of DENV E protein viz. blocking the βOG pocket which is vital for fusion.

Dengue virus entry/fusion inhibition by small bioactive molecules; A critical review

2021 ◽  
Vol 21 ◽  
Author(s):  
Podila Naresh ◽  
Shyam Sunder Pottabatula ◽  
Jubie Selvaraj
Keyword(s):  
Dengue Virus ◽  
Small Molecules ◽  
Conformational Changes ◽  
Viral Infections ◽  
Virus Entry ◽  
Antiviral Treatment ◽  
Bioactive Molecules ◽  
Fusion Process ◽  
Human Pathogens ◽  
E Protein

: Many flaviviruses are remarkable human pathogens that can be transmitted by mosquitoes and ticks. Despite the availability of vaccines for viral infections such as yellow fever, Japanese encephalitis, and tick-borne encephalitis, flavivirus-like dengue is still a significant life-threatening illness worldwide. To date, there is no antiviral treatment for dengue therapy. Industry and the research community have been taking ongoing steps to improve anti-flavivirus treatment to meet this clinical need. The successful activity has been involved in the inhibition of the virus entry fusion process in the last two decades. In this study, the latest understanding of the use of small molecules used as fusion inhibitors has been comprehensively presented. We summarized the structure, the process of fusion of dengue virus E protein (DENV E), and the amino acids involved in the fusion process. Special attention has been given to small molecules that allow conformational changes to DENV E protein viz. blocking the pocket of βOG, which is important for fusion.

scholarly journals 4,7-Disubstituted 7H-Pyrrolo[2,3-d]pyrimidines and Their Analogs as Antiviral Agents against Zika Virus

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3779
Author(s):  
Ruben Soto-Acosta ◽  
Eunkyung Jung ◽  
Li Qiu ◽  
Daniel J. Wilson ◽  
Robert J. Geraghty ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Dengue Virus ◽  
Small Molecules ◽  
Zika Virus ◽  
Antiviral Agents ◽  
Structural Features ◽  
Molecular Target ◽  
Core Structure ◽  
Human Pathogens ◽  
Important Group

Discovery of compound 1 as a Zika virus (ZIKV) inhibitor has prompted us to investigate its 7H-pyrrolo[2,3-d]pyrimidine scaffold, revealing structural features that elicit antiviral activity. Furthermore, we have demonstrated that 9H-purine or 1H-pyrazolo[3,4-d]pyrimidine can serve as an alternative core structure. Overall, we have identified 4,7-disubstituted 7H-pyrrolo[2,3-d]pyrimidines and their analogs including compounds 1, 8 and 11 as promising antiviral agents against flaviviruses ZIKV and dengue virus (DENV). While the molecular target of these compounds is yet to be elucidated, 4,7-disubstituted 7H-pyrrolo[2,3-d]pyrimidines and their analogs are new chemotypes in the design of small molecules against flaviviruses, an important group of human pathogens.

scholarly journals Possible Anti-viral effects of Neem (Azadirachta indica) on Dengue virus

2020 ◽  
Author(s):  
Vikas B Rao ◽  
Kalidas Yeturu
Keyword(s):  
Dengue Virus ◽  
Small Molecules ◽  
Azadirachta Indica ◽  
Antiviral Drug ◽  
Experimental Studies ◽  
Major Health ◽  
Molecular Binding ◽  
Scientific Curiosity ◽  
Mosquito Breeding ◽  
Health Complications

Dengue virus (DENV) has become a major health threat worldwide accounting for 50-100 million infections every year and keeping 2.5 billion people at a risk of the infection. Seriousness of the viral infection can be attributed to its lethality when not treated in time and potential to cause health complications post infection. Currently there are only preventive strategies and development of vaccination is still in its infancy of research. It is therefore highly necessary to discover newer drugs and therapies for this deadly virus. In this paper we report important insights we have obtained through a computational analysis of small molecules of Neem (Azadirachta indica) against dengue viral proteins and its required proteins in human. Our study involves identification of the effect of specific small molecules of Neem on proteins of human and virus corresponding to different pathways using simulated molecular binding analyses. We report here Gedunin and Pongamol contained in naturally occurring Neem as potential drugs against the Dengue virus.Significance StatementWe report important ligands in Neem that have potential antiviral activity against Dengue. Our selection of Neem for testing for antiviral properties has been inspired from Ayurveda. Due to unhygienic living conditions that facilitate mosquito breeding, Dengue is a major threat in developing countries causing millions of deaths. Despite the severity of the infection, no specific antiviral drug is available. The results obtained, in terms of newer potential ligands against Dengue are significant as this provides a basis for experimentally verifying and extending the same to develop a cure.We hope that this study would would spur scientific curiosity and undertaking of further elaborate experimental studies.

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.

scholarly journals Escape Mutations in NS4B Render Dengue Virus Insensitive to the Antiviral Activity of the Paracetamol Metabolite AM404

2016 ◽  
Vol 60 (4) ◽  
pp. 2554-2557 ◽  
Author(s):  
Koen W. R. van Cleef ◽  
Gijs J. Overheul ◽  
Michael C. Thomassen ◽  
Jenni M. Marjakangas ◽  
Ronald P. van Rij
Keyword(s):  
Antiviral Activity ◽  
Drug Development ◽  
Dengue Virus ◽  
Virus Replication ◽  
Disease Burden ◽  
Antiviral Drug ◽  
Virus Infections ◽  
Antiviral Compounds

ABSTRACTDespite the enormous disease burden associated with dengue virus infections, a licensed antiviral drug is lacking. Here, we show that the paracetamol (acetaminophen) metabolite AM404 inhibits dengue virus replication. Moreover, we find that mutations in NS4B that were previously found to confer resistance to the antiviral compounds NITD-618 and SDM25N also render dengue virus insensitive to AM404. Our work provides further support for NS4B as a direct or indirect target for antiviral drug development.

scholarly journals DNA-immunisation with dengue virus E protein domains I/II, but not domain III, enhances Zika, West Nile and Yellow Fever virus infection

PLoS ONE ◽  
2017 ◽  
Vol 12 (7) ◽  
pp. e0181734 ◽  
Author(s):  
Jose L. Slon Campos ◽  
Monica Poggianella ◽  
Sara Marchese ◽  
Monica Mossenta ◽  
Jyoti Rana ◽  
...  
Keyword(s):  
Virus Infection ◽  
Dengue Virus ◽  
Yellow Fever ◽  
Yellow Fever Virus ◽  
Protein Domains ◽  
Fever Virus ◽  
West Nile ◽  
E Protein ◽  
Domain Iii

scholarly journals PROFIL VIRUS DENGUE DI SURABAYA TAHUN 2008–2009

2018 ◽  
Vol 17 (1) ◽  
pp. 21
Author(s):  
Aryati . ◽  
Puspa Wardhani
Keyword(s):  
Polymerase Chain Reaction ◽  
Dengue Virus ◽  
Hemorrhagic Fever ◽  
Human Pathogens ◽  
Virus Infections ◽  
Rt Pcr ◽  
Chain Reaction ◽  
Who Criteria ◽  
Private Laboratory ◽  
Polymerase Chain

Four serotypes of dengue viruses (DENV) 1–4 are mosquito-borne human pathogens that cause widespread epidemics withconsiderable morbidity and mortality. The aim of this study was to evaluate the dengue serotypes profile, which were circulating inSurabaya. This research has been carried out consisting of 360 samples from patients with dengue virus infections, according the WorldHealth Organization (WHO) criteria. These sera were collected from patients Dr. Soetomo Hospital and private laboratory in Surabayafrom 2008–2009. From 360 samples, 68 samples (18.9%) were undifferentiated fever, 53 samples (14.7%) were dengue fever, 239samples (66.4%) were dengue hemorrhagic fever. From 58 Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) samples, 25samples (43%) were positive, consisting of 52% DEN-2, 20% DEN-1, 16% DEN-3 and 12% DEN-4. These results showed that fourserotypes are circulating in Indonesia, dominated by DEN-2, followed by DEN-1, DEN-3 and DEN-4.

scholarly journals Zika virus infection: a public health emergency!

2017 ◽  
Vol 3 (3) ◽  
pp. 68
Author(s):  
Muhammad Salman Haider Qureshi ◽  
Bakhtawar Wajeeha Qureshi ◽  
Ramsha Khan
Keyword(s):  
Public Health ◽  
West Nile Virus ◽  
Virus Infection ◽  
Dengue Virus ◽  
Yellow Fever ◽  
Zika Virus ◽  
Yellow Fever Virus ◽  
Public Health Emergency ◽  
Human Pathogens ◽  
The Family

<p class="abstract"><em>Zika virus</em> belongs to the family of Flaviviridae. The Flaviviridae family also includes other human pathogens like <em>West Nile virus</em> (WNV), <em>Yellow fever virus</em> (YFV), mosquito transmitted <em>Dengue virus</em> (DENV), <em>Tick borne encephalitic virus</em> (TBEV) and <em>Japanese encephalitis virus</em> (JEV). <em>Zika virus</em> is a mosquito-borne disease and is transmitted by <em>Aedes aegypti</em> mosquito<span lang="EN-IN">. </span></p>

scholarly journals Structure-Based Design of Antivirals against Envelope Glycoprotein of Dengue Virus

Viruses ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 367
Author(s):  
Mohd Ishtiaq Anasir ◽  
Babu Ramanathan ◽  
Chit Laa Poh
Keyword(s):  
Drug Discovery ◽  
Dengue Virus ◽  
Structural Information ◽  
Antiviral Agents ◽  
Antiviral Drug ◽  
Denv Infection ◽  
Antiviral Drugs ◽  
Global Public Health ◽  
Viral Attachment ◽  
E Protein

Dengue virus (DENV) presents a significant threat to global public health with more than 500,000 hospitalizations and 25,000 deaths annually. Currently, there is no clinically approved antiviral drug to treat DENV infection. The envelope (E) glycoprotein of DENV is a promising target for drug discovery as the E protein is important for viral attachment and fusion. Understanding the structure and function of DENV E protein has led to the exploration of structure-based drug discovery of antiviral compounds and peptides against DENV infections. This review summarizes the structural information of the DENV E protein with regards to DENV attachment and fusion. The information enables the development of antiviral agents through structure-based approaches. In addition, this review compares the potency of antivirals targeting the E protein with the antivirals targeting DENV multifunctional enzymes, repurposed drugs and clinically approved antiviral drugs. None of the current DENV antiviral candidates possess potency similar to the approved antiviral drugs which indicates that more efforts and resources must be invested before an effective DENV drug materializes.

Chapter 2b: The molecular antigenic structure of the TBEV

2020 ◽  
Keyword(s):  
Conformational Changes ◽  
Neutralizing Antibodies ◽  
Lipid Membrane ◽  
Cell Entry ◽  
Antigenic Structure ◽  
E Proteins ◽  
Amino Acid Sequence Level ◽  
Endosomal Membrane ◽  
E Protein ◽  
Golgi Network

TBEV-particles are assembled in an immature, noninfectious form in the endoplasmic reticulum by the envelopment of the viral core (containing the viral RNA) by a lipid membrane associated with two viral proteins, prM and E. Immature particles are transported through the cellular exocytic pathway and conformational changes induced by acidic pH in the trans-Golgi network allow the proteolytic cleavage of prM by furin, a cellular protease, resulting in the release of mature and infectious TBE-virions. The E protein controls cell entry by mediating attachment to as yet ill-defined receptors as well as by low-pH-triggered fusion of the viral and endosomal membrane after uptake by receptor-mediated endocytosis. Because of its key functions in cell entry, the E protein is the primary target of virus neutralizing antibodies, which inhibit these functions by different mechanisms. Although all flavivirus E proteins have a similar overall structure, divergence at the amino acid sequence level is up to 60 percent (e.g. between TBE and dengue viruses), and therefore cross-neutralization as well as (some degree of) cross-protection are limited to relatively closely related flaviviruses, such as those constituting the tick-borne encephalitis serocomplex.

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