• The Natural History, Pathobiology, and Clinical Manifestations of SARS-CoV-2 Infections

      Machhi, Jatin; Herskovitz, Jonathan; Senan, Ahmed M.; Dutta, Debashis; Nath, Barnali; Oleynikov, Maxim D.; Blomberg, Wilson R.; Meigs, Douglas D.; Hasan, Mahmudul; Patel, Milankumar; et al. (Springer Science and Business Media LLC, 2020-07-21)
      Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of coronavirus disease 2019 (COVID-19). SARS-CoV-2, is a positive-sense single-stranded RNA virus with epithelial cell and respiratory system proclivity. Like its predecessor, SARS-CoV, COVID-19 can lead to life-threatening disease. Due to wide geographic impact affecting an extremely high proportion of the world population it was defined by the World Health Organization as a global public health pandemic. The infection is known to readily spread from person-to-person. This occurs through liquid droplets by cough, sneeze, hand-to-mouth-to-eye contact and through contaminated hard surfaces. Close human proximity accelerates SARS-CoV-2 spread. COVID-19 is a systemic disease that can move beyond the lungs by blood-based dissemination to affect multiple organs. These organs include the kidney, liver, muscles, nervous system, and spleen. The primary cause of SARS-CoV-2 mortality is acute respiratory distress syndrome initiated by epithelial infection and alveolar macrophage activation in the lungs. The early cell-based portal for viral entry is through the angiotensin-converting enzyme 2 receptor. Viral origins are zoonotic with genomic linkages to the bat coronaviruses but without an identifiable intermediate animal reservoir. There are currently few therapeutic options, and while many are being tested, although none are effective in curtailing the death rates. There is no available vaccine yet. Intense global efforts have targeted research into a better understanding of the epidemiology, molecular biology, pharmacology, and pathobiology of SARS-CoV-2. These fields of study will provide the insights directed to curtailing this disease outbreak with intense international impact.
    • Pharmacotherapeutics of SARS-CoV-2 Infections

      Kevadiya, Bhavesh D; Machhi, Jatin; Herskovitz, Jonathan; Oleynikov, Maxim D; Blomberg, Wilson R; Bajwa, Neha; Soni, Dhruvkumar; Das, Srijanee; Hasan, Mahmudul; Patel, Milankumar; et al. (Springer Nature, 2021-01-06)
      The COVID-19 pandemic has affected more than 38 million people world-wide by person to person transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therapeutic and preventative strategies for SARS-CoV-2 remains a significant challenge. Within the past several months, effective treatment options have emerged and now include repurposed antivirals, corticosteroids and virus-specific antibodies. The latter has included convalescence plasma and monoclonal antibodies. Complete viral eradication will be achieved through an effective, safe and preventative vaccine. To now provide a comprehensive summary for each of the pharmacotherapeutics and preventative strategies being offered or soon to be developed for SARS-CoV-2. Graphical abstract: [Figure not available: see fulltext.].
    • A Role for Extracellular Vesicles in SARS-CoV-2 Therapeutics and Prevention

      Machhi, Jatin; Shahjin, Farah; Das, Srijanee; Patel, Milankumar; Abdelmoaty, Mai Mohamed; Cohen, Jacob D; Singh, Preet Amol; Baldi, Ashish; Bajwa, Neha; Kumar, Raj; et al. (Springer Nature, 2021-02-05)
      Extracellular vesicles (EVs) are the common designation for ectosomes, microparticles and microvesicles serving dominant roles in intercellular communication. Both viable and dying cells release EVs to the extracellular environment for transfer of cell, immune and infectious materials. Defined morphologically as lipid bi-layered structures EVs show molecular, biochemical, distribution, and entry mechanisms similar to viruses within cells and tissues. In recent years their functional capacities have been harnessed to deliver biomolecules and drugs and immunological agents to specific cells and organs of interest or disease. Interest in EVs as putative vaccines or drug delivery vehicles are substantial. The vesicles have properties of receptors nanoassembly on their surface. EVs can interact with specific immunocytes that include antigen presenting cells (dendritic cells and other mononuclear phagocytes) to elicit immune responses or affect tissue and cellular homeostasis or disease. Due to potential advantages like biocompatibility, biodegradation and efficient immune activation, EVs have gained attraction for the development of treatment or a vaccine system against the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) infection. In this review efforts to use EVs to contain SARS CoV-2 and affect the current viral pandemic are discussed. An emphasis is made on mesenchymal stem cell derived EVs’ as a vaccine candidate delivery system. Graphical Abstract: [Figure not available: see fulltext.]. © 2021, The Author(s)