The concept of Big Four: Road map from snakebite epidemiology to antivenom efficacy.

Snake envenomation is a life-threatening disease caused by the injection of venom toxins from the venomous snake bite. Snakebite is often defined as the occupational or domestic hazard mostly affecting the rural population. India experiences a high number of envenoming cases and fatality due to the nation's diversity in inhabiting venomous snakes. The Indian Big Four snakes namely Russell's viper (Daboia russelii), spectacled cobra (Naja naja), common krait (Bungarus caeruleus), and saw-scaled viper (Echis carinatus) are responsible for majority of the snake envenoming cases and death. The demographic characteristics including occupation, stringent snake habitat management, poor healthcare facilities and ignorance of the rural victims are the primary influencers of high mortality. Biogeographic venom variation greatly influences the clinical pathologies of snake envenomation. The current antivenoms against the Big Four snakes are found to be less immunogenic against the venom toxins emphasizing the necessity of alternative approaches for antivenom generation. This review summarizes the burden of snake envenomation in India by the Big Four snakes including the geographic distribution of snake species and biogeographic venom variation. We have provided comprehensive information on snake venom proteomics that has aided the better understanding of venom induced pathological features, summarized the impact of current polyvalent antivenom therapy highlighting the need for potential antivenom treatment for the effective management of snakebites.

Targeting the viral-entry facilitators of SARS-CoV-2 as a therapeutic strategy in COVID-19.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19) infection, which has emerged as a global pandemic causing serious concerns. Lack of specific and effective therapeutics for the treatment of COVID-19 is a major concern and the development of vaccines is another important aspect in managing the infection effectively. The first step in the SARS-CoV-2 pathogenesis is the viral entry and it is mediated by its densely glycosylated spike protein (S-protein). Similar to the SARS-CoV, SARS-CoV-2 also engages angiotensin-converting enzyme 2 (ACE2) as the host cell entry receptor. In addition to ACE2, several recent studies have implicated the crucial role of cell surface heparan sulfate (HS) as a necessary assisting cofactor for ACE2-mediated SARS-CoV-2 entry. Furthermore, SARS-CoV-2 was also identified to use both endosomal cysteine proteases cathepsin B and L (CatB/L) and the transmembrane serine protease 2 (TMPRSS2) for the pivotal role of S-protein priming mediating viral entry. As the entry of SARS-CoV-2 into host cells is mandatory for viral infection, it becomes an extremely attractive therapeutic intervention point. In this regard, this review will focus on the therapeutic targeting of the crucial steps of SARS-CoV-2 viral entry like S-protein/ACE2 interaction and S-protein priming by host cell proteases. In addition, this review will also give insights to the readers on several therapeutic opportunities, pharmacological targeting of the viral-entry facilitators like S-Protein, ACE2, cell surface HS, TMPRSS2, and CatB/L and evidence for those drugs currently ongoing clinical studies.

The emergence of COVID-19 as a global pandemic: Understanding the epidemiology, immune response and potential therapeutic targets of SARS-CoV-2.

An acute respiratory disease caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that surfaced in China in late 2019, continues to spread rapidly across the globe causing serious concerns. The coronavirus disease 2019 (COVID-19) is declared as a public health emergency worldwide by the World Health Organization (WHO). Increasing evidences have demonstrated human-to-human transmission that primarily affects the upper respiratory tract followed by lower respiratory tract damage leading to severe pneumonia. Based on the current status, the elderly population and people with prior co-morbidities are highly susceptible to serious health effects including cytokine up-regulation and acute respiratory distress syndrome (ARDS). Currently, COVID-19 research is still in the preliminary stage necessitating rigorous studies. There is no specific drug or vaccine targeting SARS-CoV-2 currently and only symptomatic treatment is being administered, but several antivirals are under active investigation. In this review, we have summarized the epidemiology, entry mechanism, immune response, and therapeutic implications, possible drug targets, their ongoing clinical trials, and put forward vital questions to offer new directions to the COVID-19 research.

Role of tau protein in Alzheimer's disease: The prime pathological player.

Alzheimer's disease (AD) is a prevalently found tauopathy characterized by memory loss and cognitive insufficiency. AD is an age-related neurodegenerative disease with two major hallmarks which includes extracellular amyloid plaques made of amyloid-ß (Aß) and intracellular neurofibrillary tangles of hyperphosphorylated tau. With population aging worldwide, there is an indispensable need for treatment strategies that can potentially manage this developing dementia. Despite broad researches on targeting Aß in the past two decades, research findings on Aß targeted therapeutics failed to prove efficacy in the treatment of AD. Tau protein with its extensive pathological role in several neurodegenerative diseases can be considered as a promising target candidate for developing therapeutic interventions. The abnormal hyperphosphorylation of tau plays detrimental pathological functions which ultimately lead to neurodegeneration. This review will divulge the importance of tau in AD pathogenesis, the interplay of Aß and tau, the pathological functions of tau, and potential therapeutic strategies for an effective management of neuronal disorders.

Inflammation in myocardial injury- Stem cells as potential immunomodulators for myocardial regeneration and restoration.

The ineffective immunosuppressant's and targeted strategies to neutralize inflammatory mediators have worsened the scenario of heart failure and have opened many questions for debate. Stem cell therapy has proven to be a promising approach for treating heart following myocardial infarction (MI). Adult stem cells, induced pluripotent stem cells and embryonic stem cells are possible cell types and have successfully shown to regenerate damaged myocardial tissue in pre-clinical and clinical studies. Current implications of using mesenchymal stem cells (MSCs) owing to their immunomodulatory functions and paracrine effects could serve as an effective alternative treatment option for rejuvenating the heart post MI. The major setback associated with the use of MSCs is reduced cell retention, engraftment and decreased effectiveness. With a few reports on understanding the role of inflammation and its dual effects on the structure and function of heart, this review focuses on these missing insights and further exemplifies the role of MSCs as an alternative therapy in treating the pathological consequences in myocardial infarction (MI).