Identification of sequence motifs involved in Dengue virus-host interactions.

Dengue fever is a rapidly spreading mosquito-borne virus infection, which remains a serious global public health problem. As there is no specific treatment or commercial vaccine available for effective control of the disease, the attempts on developing novel control strategies are underway. Viruses utilize the surface receptor proteins of host to enter into the cells. Though various proteins were said to be receptors of Dengue virus (DENV) using Virus Overlay Protein Binding Assay, the precise interaction between DENV and host is not explored. Understanding the structural features of domain III envelope glycoprotein would help in developing efficient antiviral inhibitors. Therefore, an attempt was made to identify the sequence motifs present in domain III envelope glycoprotein of Dengue virus. Computational analysis revealed that the NGR motif is present in the domain III envelope glycoprotein of DENV-1 and DENV-3. Similarly, DENV-1, DENV-2 and DENV-4 were found to contain Yxxphi motif which is a tyrosine-based sorting signal responsible for the interaction with a mu subunit of adaptor protein complex. High-throughput virtual screening resulted in five compounds as lead molecules based on glide score, which ranges from -4.664 to -6.52 kcal/Mol. This computational prediction provides an additional tool for understanding the virus-host interactions and helps to identify potential targets in the host. Further, experimental evidence is warranted to confirm the virus-host interactions and also inhibitory activity of reported lead compounds.

DENVirDB: a web portal of dengue virus sequence information on Asian isolates.

DENVirDB is a web portal that provides the sequence information and computationally curated information of dengue viral proteins. The advent of genomic technology has increased the sequences available in the public databases. In order to create relevant concise information on Dengue Virus (DENV), the genomic sequences were collected, analysed with the bioinformatics tools and presented as DENVirDB. It provides the comprehensive information of complete genome sequences of dengue virus isolates of Southeast Asia, viz. India, Bangladesh, Sri Lanka, East Timor, Philippines, Malaysia, Papua New Guinea, Brunei and China. DENVirDB also includes the structural and non-structural protein sequences of DENV. It intends to provide the integrated information on the physicochemical properties, topology, secondary structure, domain and structural properties for each protein sequences. It contains over 99 entries in complete genome sequences and 990 entries in protein sequences, respectively. Therefore, DENVirDB could serve as a user friendly database for researchers in acquiring sequences and proteomic information in one platform.

Identification of structural motifs in the E2 glycoprotein of Chikungunya involved in virus-host interaction.

Chikungunya fever is one of the reemerging vector-borne diseases. It has become a major global health problem especially in the developing countries. There are no vaccines or specific antiviral drugs available to date. This study reports small molecule inhibitors of envelope glycoprotein 2 (E2 glycoprotein) which are predicted based on Chikungunya virus-host interactions. E2 glycoprotein of Chikungunya virus interacts at 216 residue of the host receptor protein which plays a vital role in initiating infection. Understanding the structural aspects of E2 glycoprotein is crucial to develop specific inhibitors to prevent the virus binding from host receptors. In silico method was adopted to predict the sequence motifs of envelope protein, as the method like yeast two hybrid system is laborious, time consuming, and costly. The E2 glycoprotein structure of the Indian isolate was modeled using two templates (2XFC and 3JOC) and then validated. The class III PDZ domain binding motif was found to be identified at 213-216 amino acids. The corresponding peptide structures which recognize the PDZ domain binding motif were identified by the literature search and were used for generating five point pharmacophore model (ADDDR) containing acceptor, donor and aromatic ring features. Databases such as Asinex, TosLab and Maybridge were searched for the matches for the predicted pharmacophore model. Two compounds were identified as lead molecules as their glide score is > 5 kcal/mol. Since the pharmacophore model is developed based on Chikungunya virus-host interaction, it can be used for designing promising antiviral lead compounds for the treatment of Chikungunya fever.An animated Interactive 3D Complement (I3DC) is available in Proteopedia at http://proteopedia.org/w/Journal:JBSD:21.