Transmission of SARS-CoV-2, Required Developments in Research and Associated Public Health Concerns

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is rapidly spreading across the world to cause thousands of mortalities each day. Poor responses from the authorities to the spread of infection, lack of effective measures for prevention, unavailability of promising treatment options, and sufficient diagnostic options have created an alarming for the world. The transmission routes from human to human of SARS-CoV-2 can be the direct transmission, droplet inhalation transmission, contact transmission, transmission through saliva, and transmission via fecal-oral routes. Due to the asymptomatic spread of SARS-CoV-2's, developing control and prevention measures is challenging. Implementing proper strategies addressing the infection control and clinical supplies, understanding the mechanism associated with pathogenesis, advancing in preventive measures and effective treatment and diagnostic options are necessary to control the ongoing pandemic. In this article, we briefly discuss the features, entry mechanism, infectiousness, and health consequences related to the COVID-19 outbreak.

Keywords: challenges; coronavirus outbreak; infectiousness; medical consequences; prevention.

Figure 1

The most common entry to host cells mechanisms of human viruses. (A) SARS-CoV entry. Key points are, virion attachment to receptor; virion internalization by endocytosis; lowering the pH (5.5) of the endocytic vacuole leading to drastic reconfiguration of the viral attachment protein; insertion into the vacuolar membrane; fusion of vacuolar membranes and the viral; viral nucleocapsid release into the cytosol. (B) Poliovirus entry. virion binding to cell surface receptors, endocytosed and ultimately delivered to endosomes (low pH); conformational changes in viral capsid due to low pH environment result in exposure of hydrophobic domains that insert into the endosomal membrane, producing a pore for viral genome exit and entry into cytoplasm. (C) HIV entry. Virion attaches to various attachment factor on cell surface, such as DC-SIGN. The attachment of viral envelope glycoprotein to CD4 alters the structure of envelope glycoprotein, which then induces the second receptor binding domain exposure resulting in the engagement of CCR5 or CXCR4 coreceptors, that in turn causes the viral fusion with the cell membrane.

Figure 2

The SARS-CoV-2 transmission from bats via unknown intermediate to humans causes infectiousness known as COVID-19 disease. The binding of S protein to ACE2 receptor initiates the life cycle which is then followed by conformational changes in the S protein, which further facilitates the fusion of viral envelope and host cell membrane. Following the fusion through endosomal pathway, SARS-CoV-2 then releases RNA into the host cell, which is translated into pp1a and pp1ab. Next, viral proteinases cleave the translated proteins into small products, meanwhile a series of sub-genomic mRNAs are produced by polymerase enzyme through discontinuous transcription, which are then translated into specific viral proteins. These viral proteins and genome RNA are assembled to form virions in Golgi and endoplasmic reticulum, which are later transported out of the cell via vesicles. This figure was designed by updating and modifying the information from our previously published paper (29).