Coronavirus Disease 19 (COVID-19), due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become an on-going global health emergency affecting over 94 million cases with more than 2 million deaths globally. Primarily identified as atypical pneumonia, it has developed into severe acute respiratory distress syndrome (ARDS), a multi-organ dysfunction with associated fatality. Ever since its emergence, COVID-19 with its plethora of clinical presentations has signalled its dynamic nature and versatility of the disease process. Being a disease with droplet transmission has now assumed the proportion of a suspected airborne nature which, once proved, poses a Herculean task to control. Because of the wide distribution of the human angiotensin-converting enzyme-2 (hACE2) receptors, known for its transmission, we envisage its multiorgan spread and extensive disease distribution. Thus, an extensive review of the extrapulmonary organotropism of SARS-CoV-2 with organ-specific pathophysiology and associated manifestations like dermatological complications, myocardial dysfunction, gastrointestinal symptoms, neurologic illnesses, hepatic and renal injury is needed urgently. The plausible mechanism of site-specific viral invasion is also discussed to give a comprehensive understanding of disease complexity, to help us to focus on research priorities and therapeutic strategies to counter the disease progression. A note on the latest advancements in vaccine research will enlighten the scientific world and equip it for better preparedness.

Hepatitis E viral infection recently emerges as a global health concern. Over the last decade, the understanding of hepatitis E virus (HEV) had changed with the discovery of new genotypes like genotype-7 and genotype-8 with associated host and mode of infection. Diversification in the mode of hepatitis E infection transmission through blood transfusion, and organ transplants in contrast to classical feco-oral and zoonotic mode is the recent medical concern. The wide spectrum of infection ranging from self-limiting to acute liver failure is now overpowered by HEV genotype-specific chronic infection especially in transplant patients. This concern is further escalated by the extra-hepatic manifestations of HEV targeting the central nervous system (CNS), kidney, heart, and pancreas. However, with the development of advanced efficient cell culture systems and animal models simulating the infection, much clarity toward understanding the pathogenetic mechanism of HEV has been developed. Also this facilitates the development of vaccines research or therapeutics. In this review, we highlight all the novel findings in every aspect of HEV with special emphasis on recently emerging chronic mode of infection with specific diagnosis and treatment regime with an optimistic hope to help virologists and/or liver specialists working in the field of viral hepatitis.

Viral hepatitis E is an under-estimated clinical entity with high mortality (20%-30%), especially in the third trimester of pregnancy. As complications due to hepatitis E virus (HEV) in pregnancy is much greater, it is hypothesized that HEV may cross the placenta and replicate in placental tissues even weeks after clearance from the blood, and cytokines may play a role in the immunopathogenesis of HEV in pregnancy. A total of 12 pregnant women with features of acute viral hepatitis/ acute liver failure and positive for either HEV-immunoglobulin M (IgM)/HEV-RNA and 30 pregnant women negative for HEV RNA/IgM/immunoglobulin G were enrolled as study subjects and healthy controls, respectively. Following delivery, 5 ml blood was collected from the mother for HEV-RNA. Replicative RNA and viral load in placental tissue were detected through Real-Time PCR. Placental tissues from the maternal/fetal sides were stained for HEV antigen using HEV-open reading frame-2 antibody by immunohistochemistry (IHC) and for histopathological changes by haematoxylin and eosin. Plasma samples were tested for interleukin (IL)-1β and IL-18 cytokine levels using Duo-R&D ELISA kit, whereas peripheral blood mononuclear cells were used to study the inflammasomes and IL-1β and IL-18 cytokine genes expression.Of the 10 HEV RNA-positive sera, 9 had HEV RNA either in the maternal/fetal side of the placenta with the mean viral load of 137.4 IU/ml. Of the 10 HEV RNA-positive pregnant women, stillbirth in two and fetal and maternal death in one case was reported. IHC revealed strong brownish cytoplasmic staining (HEV antigen) in cytotrophoblasts and syncytiotrophoblast cells in positive samples. The maternal/fetal side of the infected placenta showed irregular intervillous fibrin deposition as well as tissue necrosis. The mean levels of IL-1β and IL-18 cytokines in serum of infected subjects were significantly higher than the healthy controls (17.31 ± 4.462 vs. 8.85 ± 4.36 pg/ml; p < 0.0001*** and 2275 ± 536.9 vs. 1085 ± 531.7 pg/ml; p < 0.0001***), respectively. Detecting replicative HEV RNA and HEV antigen in placental tissues indicated the extra-hepatic replication of HEV. Furthermore, placental tissue necrosis and significant rise of cytokine levels in

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Hepatitis E viral infection is now emerging as a global health concern, which needs to be addressed. Mechanism of viral replication and release is attributed by the different genomic component of HEV. However, few proteins/domain like X and Y domain remain unexplored, so we aim to explore the physiochemical, structural and functional features of HEV ORF-1 X domain. Molecular modeling of the unknown X domain was carried out using Phyre2 and Swiss Model. Active ligand binding sites were predicted using Phyre2. The X-domain protein found to be stable and acidic in nature with high thermostability and better hydrophilic property. Twelve binding sites were predicted along with putative transferase and catalytic functional activity. Homology modeling showed 10 binding sites along with Mg2+ and Zn2+ as metallic heterogen ligands binding to predicted ligand-binding sites. This study may help to decipher the role of this unexplored X-domain of HEV, thereby improving our understanding of the pathogenesis of HEV infection.