Viral Pandemics of the Last Four Decades: Pathophysiology, Health Impacts and Perspectives

Abstract

The last four decades has witnessed some of the deadliest viral pandemics with far-reaching consequences. These include the Human Immunodeficiency Virus (HIV) (1981), Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) (2002), Influenza A virus subtype H1N1 (A/H1N1) (2009), Middle East Respiratory Syndrome Coronavirus (MERS-CoV) (2012), Ebola virus (2013) and the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) (2019-present). Age- and gender-based characterizations suggest that SARS-CoV-2 resembles SARS-CoV and MERS-CoV with regard to higher fatality rates in males, and in the older population with comorbidities. The invasion-mechanism of SARS-CoV-2 and SARS-CoV, involves binding of its spike protein with angiotensin-converting enzyme 2 (ACE2) receptors; MERS-CoV utilizes dipeptidyl peptidase 4 (DPP4), whereas H1N1 influenza is equipped with hemagglutinin protein. The viral infections-mediated immunomodulation, and progressive inflammatory state may affect the functions of several other organs. Although no effective commercial vaccine is available for any of the viruses, those against SARS-CoV-2 are being developed at an unprecedented speed. Until now, only Pfizer/BioNTech’s vaccine has received temporary authorization from the UK Medicines and Healthcare products Regulatory Agency. Given the frequent emergence of viral pandemics in the 21st century, proper understanding of their characteristics and modes of action are essential to address the immediate and long-term health consequences.

Viral Pandemics of Twenty-First Century

“…In case of Ebola outbreak, adults above 30 years of age were found to be the most effected, with no significant biological differences in gender-based susceptibility (Bower et al, 2016;Nkangu et al, 2017). During the recent SARS-CoV-2 outbreak, patients above 60 years of age were found to be suffering from more severe symptoms, along with increased risk of death in such patients (Roychoudhury et al, 2020;Liu et al, 2020). While men and women have equal prevalence of disease occurrence, the death rate of SARS-CoV-2 infected males is about 2.4 times more than that of infected females (Jin et al, 2020).…”

“…Once inside the cell, the virus hijacks the cellular machinery to produce viral proteins which help in replication of the viral genome (Cohen, 2016). SARS-CoV and MERS-CoV uses angiotensin-converting enzyme 2 (ACE2) and dipeptidyl peptidase 4 (DPP4) respectively as the cell surface proteins to gain access into the host cell (Li et al, 2003;Kuba et al, 2010;Raj et al, 2013;Roychoudhury et al, 2020). This is followed by proteolytic cleavage of viral spike proteins which leads to the fusion of viral and host cell membranes in the acidic environment of the endosome, which eventually leads to the release of viral genome into the cytosol (Bosch et al, 2003;Fehr and Perlman, 2015).…”

“…Significant policy attention is required to limit the outbreak of such pandemics and to expand and sustain investment to build preparedness and health capacity. H1N1 Influenza A virus undergoes hemagglutinin-mediated binding to the receptor which results in endocytosis through clathrin-dependent manner or through macropinocytosis (Roy et al, 2000;Rust et al, 2004;Roychoudhury et al, 2020). This is followed by opening of matrix 2 protein ion channel, which acidifies the inside of the viral particle and subsequently releases viral RNA (Martin and Helenius, 1991;Rust et al, 2004).…”

“…Vaccines against SARS-CoV-2 are being developed at an unprecedented speed (Roychoudhury et al, 2020). As of 29 th December 2020, 172 vaccine candidates are in pre-clinical development and 60 vaccine candidates are in clinical trial phases, 11 of which are in phase 3 clinical trial stage (WHO, 2020).…”

“…Since the dawn of mankind, there has been a constant quest to overcome the threat of infectious diseases. The 21 st century has been no exception as humanity experienced the emergence of several viral outbreaks, of which Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) in 2002, Influenza A virus subtype H1N1 (H1N1) in 2009, Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in 2012, Ebola virus in 2013 and the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) in 2019-present, are noteworthy (Zappa et al, 2009;Bloom and Cadarette, 2019;Grubaugh et al, 2019;Cascella et al, 2020;Roychoudhury et al, 2020).. Such epidemics helped in identifying the shortcomings of public healthcare system and provided opportunities to rapid and effective research on basic scientific aspects of these diseases in order to better prepare for future outbreaks.…”