COVID-19 and its genomic variants: Molecular pathogenesis and therapeutic interventions

Abstract

Coronavirus disease-19 (COVID-19), caused by a β-coronavirus and its genomic variants, is associated with substantial morbidities and mortalities globally. The COVID-19 virus and its genomic variants enter host cells upon binding to the angiotensin converting enzyme 2 receptors that are expressed in a variety of tissues, but predominantly in the lungs, heart, and blood vessels. Patients afflicted with COVID-19 may be asymptomatic or present with critical symptoms possibly due to diverse lifestyles, immune responses, aging, and underlying medical conditions. Geriatric populations, especially men in comparison to women, with immunocompromised conditions, are most vulnerable to severe COVID-19 associated infections, complications, and mortalities. Notably, whereas immunomodulation, involving nutritional consumption, is essential to protecting an individual from COVID-19, immunosuppression is detrimental to a person with this aggressive disease. As such, immune health is inversely correlated to COVID-19 severity and resulting consequences. Advances in genomic and proteomic technologies have helped us to understand the molecular events underlying symptomatology, transmission and, pathogenesis of COVID-19 and its genomic variants. Accordingly, there has been development of a variety of therapeutic interventions, ranging from mask wearing to vaccination to medication. This review summarizes the current understanding of molecular pathogenesis of COVID-19, effects of comorbidities on COVID-19, and prospective therapeutic strategies for the prevention and treatment of this contagious disease.

Keywords: COVID-19 and its variants; healthy immunity; immunocompromised conditions; lifestyle; pathogenesis; therapeutics.

Table 1. Vitamins, their major sources, RDA values for adults, and various functions

Table 2. Influence of a variety of practices and/or measures for the prevention of COVID-19 and its variants

Table 3. Potential therapeutic interventions for the treatment of COVID-19 and its variants

Figure 1. Schematic representation of a COVID-19 virus and its different components including the spike protein (blue), plasma membrane (red circle), nucleocapsid proteins (green circles), positive sense single stranded RNA (black lines), ACE2 receptor (yellow umbrella-shaped), and the envelope protein (pink triangles). The spike protein is further magnified to show various parts including the receptor binding pocket and its binding to the ACE2 receptor (yellow) (A). Entry of the COVID-19 virus into a body cell upon binding, cleavage, and fusion to the ACE2 receptors. Initial +ssRNA is translated using host cellular machinery to make the viral replication complex within the host endoplasmic reticulum (ER). This complex is then used in conjunction with the +ssRNA to make -ssRNA copies that allow for genomic duplication. These duplicates are then translated to make all the virus specific proteins. The host ER then positions all viral proteins for subsequent migration to the Golgi Body (GB). As the vesicle is moved to the GB, it engulfs a copy of the +ssRNA viral genome and forms a virion (B). The virion is migrated to the plasma membrane where it is expulsed and can now infect new somatic cells or cells of another individual. Retrieved and revised from https://app.biorender.com.

Figure 2. Schematic representation revealing the potential target of the COVID-19 virus or its variants to various organs expressing the ACE2 receptors. The organ/organ systems shown are the brain, stomach, gallbladder, liver, kidney, colon, small intestines, nasal cavities, esophagus, lungs, heart, and blood vessels. Different organs with the ACE2 receptor expression are arbitrarily depicted as + (low), ++ (medium), and +++/++++ (high), thus, demonstrating the diverse ability of these viruses to infect respective organs and result in clinical negative outcomes for the patient. Retrieved and revised from https://app.biorender.com.

Figure 3. Graphical representation illustrating the impact of COVID-19 to men and women possessing either a strengthened immune system or an impaired immune system. Individuals maintaining healthy immunity/immunomodulation (upper section), effected by vitamins, minerals, and nutrients, are generally protective against COVID-19 (middle) linked infections and resulting consequences. On the other hand, people with immunocompromised conditions (lower section), affected by underlying medical situations, including aging, obesity, cancers, neurological disease, and diabetes are most vulnerable to severe COVID-19 associated infections and complications, with fatal outcomes.

Figure 4. Diagrammatic representation of COVID-19 acting on various lifestyles. Left panel shows healthy male/female and child/adult. Due to their healthy lifestyle choices, adequate intake of nutrients, consistent physical activity, and no underlying conditions, they can present a positive disease outlook. This indicates that the majority of those with healthy lifestyles will muster effective immune responses, quick recoveries, low mortalities, and few hospitalizations. Conversely, right panels show unhealthy individuals presenting opposite conditions as those of healthy individuals. They will majorly experience less effective immune responses, longer recovery times, more long-term effects, higher mortalities, and more hospitalizations. However, both groups can greatly benefit from prevention techniques including wearing facial coverings, physical distancing, adequate handwashing, and receiving a COVID-19 vaccine.

Figure 5. Modes of action of a variety of drugs such as monoclonal antibodies, Remdesivir, and Molnupiravir, against COVID-19. Whereas monoclonal antibodies encompass COVID-19 and occupy the spike protein inhibiting cell binding, Remdesivir block the COVID-19 replication process in a human host cell. Molnupiravir, an oral drug, enters a host cell that is infected by actively replicating COVID-19 viruses, in which it acts as a nucleoside analog that can insert itself into the viral RNA genome. These insertions limit/destroy the original translational function of the genome and lead to the creation of non-functioning COVID-19 proteins that inhibit the virus's ability to replicate and transmit to others. Retrieved and revised from http://app.biorender.com.