Viruses are not living cells or organisms. They are obligate parasites or nonliving organisms that lack metabolic machinery of their own to generate energy or synthesize proteins. Rather, they require a living host to exploit or infect (enter) so they can replicate to complete their life cycle (see Fig. 7.1 and Life Cycle below). The invading virus uses either its genomic DNA or RNA to replicate in the host cell. Coronaviruses (CoV) are a family of RNA viruses that typically cause mild respiratory disease in humans thought to be driven by the spillover of bat-adapted CoVs into an intermediate host. The novel coronavirus (SARS-CoV-2) is a single positive-strand RNA virus poorly adapted to the human host. If it is transmitted to humans, it is generally associated with more severe clinical presentations. Also, if infection occurs (and subsequent mutations), it can be highly transmissible from person to person as SARS-CoV-2 has demonstrated.
Researchers have analyzed genomic data related to the overall molecular structure of the new coronavirus. Their testing has traced this novel coronavirus to a strain of Malaysian anteater (pangolin) containing genomic regions that are very closely related to the human virus. Their analysis showed that the genome resembles that of a bat coronavirus discovered after the COVID-19 pandemic began. However, in “SARS-CoV-2 testing,” the binding region of the spike protein resembles the novel virus found in pangolins (anteaters). This provides additional evidence that the coronavirus that causes COVID-19 almost certainly originated in nature, most likely in bats with an intermediate animal (anteater or monkey?) host and ultimately transmitted to humans (“zoonotic spillover”).
This genetic information concludes that “coronaviruses clearly have the capacity to jump species boundaries and adapt to new hosts” (anthroponotic being reported between domestic and zoo animals). Most important among these findings is the receptor binding domain (spike protein) that dictates how the virus is able to attach and infect human cells. This comparative analysis of genomic data dispelled the postulate that the virus was laboratory constructed or was a “manipulated” virus. Rather, it promotes a lesson learned to reduce human exposure to wildlife and to ban the trade and consumption (e.g., “wet markets” in China) of wildlife.
The genomic data of the new coronavirus show that its spike protein contains some unique adaptations. One of these adaptations provides special ability of this coronavirus to bind to a specific protein on human cells called angiotensin-converting enzyme (ACE-2). Human ACE-2 is expressed in epithelial cells of the lung and serves as an entry receptor site for SARS-CoV-2 spike protein. Finally, an interesting finding was made among SARS-CoV-2-infected patients. Researchers found a haplotype (a group of genes inherited together from a single parent) on chromosome 12 that reduces the risk of severe Covid-19 infection. This genetic mutation is associated with about a 22% reduction in the relative risk of becoming severely ill with COVID-19 when infected by SARS-CoV-2. This region encodes proteins that activate enzymes (proteases) that are important during infections with RNA viruses. The genetic region involved affects the body’s immune response to RNA viruses such as the coronavirus. This is a mutation that has been passed down over the millennia because it is assumed to help people survive the frequent viral infections among humans.
Discussion Question:
The novel coronavirus (SARSCoV-2) is a single positive-strand RNA virus poorly adapted to the human host. What 2 significant clinical effects are associated with single positive-strand RNA virus?
The genomic data of the new coronavirus show that its spike protein contains some unique adaptations. It has the ability to bind to angiotensin-converting enzyme (ACE-2). What is the clinical significance of this feature?
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