Analyses of spike protein from first deposited sequences of SARS-CoV2 from West Bengal, India.

India has recently started sequencing SARS-CoV2 genome from clinical isolates. Currently only few sequences are available from three states in India. Kerala was the first state to deposit complete sequence from two isolates followed by one from Gujarat. On April 27, 2020, the first five sequences from the state of West Bengal (Eastern India) were deposited on GISAID, a global initiative for sharing avian flu data. In this study, we have analysed the spike protein sequences from all five isolates and also compared their similarities or differences with other sequences reported in India and with isolates of Wuhan origin. We report one unique mutation at position 723 and another at 1124 in the S2 domain of spike protein of the isolates from West Bengal only.  There was one mutation downstream of the receptor binding domain at position 614 in S1 domain which was common with the sequence from Gujarat (a state of western India).  Mutation in the S2 domain showed changes in the secondary structure of the spike protein at region of the mutation. We also studied molecular dynamics using normal mode analyses and found that this mutation decreases the flexibility of S2 domain.  Since both S1 and S2 are important in receptor binding followed by entry in the host cells, such mutations may define the affinity or avidity of receptor binding.

The Mosquito Immune System and the Life of Dengue Virus: What We Know and Do Not Know.

Flaviviruses are largely transmitted to humans by their arthropod vectors such as mosquitoes or ticks. The dengue virus (DENV) is one of the members of the family Flaviviridae and is the causative agent of dengue fever. In the mosquito vector, DENV enters through viremic blood meal and replicates in the mid-gut. Newly formed virion particles circulate to various mosquito organs and get transmitted to the next host in subsequent bites. Aedes aegypti and Aedes albopictus have intricate immune control to allow DENV production at a sub-pathogenic level. In the mosquito, antimicrobial peptides (AMP) and RNA inference (RNAi) are the two main antiviral strategies used against DENV. Apart from innate immunity, mosquito resident microbes play a significant role in modulating DENV replication. In this review, we discuss different immune mechanisms and preventive strategies that act against DENV in two of its vectors: Aedes aegypti and Aedes albopictus.

Insight into the Tropism of Dengue Virus in Humans.

In tropical and subtropical zones, arboviruses are among the major threats to human life, affecting a large number of populations with serious diseases. Worldwide, over three hundred million people are infected with dengue virus (DENV) every year as per the World Health Organization (WHO). DENV-mediated disease severity ranges from a mild fever to hemorrhagic fever and shock syndrome. Patients suffering from severe infection might experience multi-organ failure, cardiomyopathy and even encephalopathy, further complicating the disease pathogenesis. In life-threatening cases, DENV has been reported to affect almost all organs of the human body. In this review, we discuss the organ tropism of DENV in humans in depth as detected in various autopsy studies. Keeping in mind the fact that there is currently no DENV-specific antiviral, it is of utmost importance to achieve a vivid picture of the susceptible cells in humans which might help in designing antivirals against DENV, especially targeting those tissues in which infection might lead to life-threatening conditions.

Hijacking the Host Immune Cells by Dengue Virus: Molecular Interplay of Receptors and Dengue Virus Envelope.

Dengue virus (DENV) is one of the lethal pathogens in the hot climatic regions of the world and has been extensively studied to decipher its mechanism of pathogenesis and the missing links of its life cycle. With respect to the entry of DENV, multiple receptors have been recognized in different cells of the human body. However, scientists still argue whether these identified receptors are the exclusive entry mediators for the virus. Adding to the complexity, DENV has been reported to be infecting multiple organ types in its human host. Also, more than one receptor in a particular cell has been discerned to take part in mediating the ingress of DENV. In this review, we aim to discuss the different cells of the human immune system that support DENV infection and their corresponding receptors that DENV deploy to gain access to the cells.