COVID-19: Background Science to Understand the Pandemic

Pathogenic RNA viruses began to prey in earnest on humans around the time of our industrial revolution. As the human population exploded and then increased its density by a massive effort of urbanization, it also changed land use to encroach on wildlife. Such changes continue today, unabated, even accelerated, as the human population attempts to achieve its final doubling. There is currently tremendous encroachment on wild animals. Many of these animals host populations of bacteria and viruses that are pathogenic to humans, and every day more wild animals are brought into contact with other animals that are meant as companions or food for humans. This situation is a perfect set up for epidemics and pandemics. Some major ones are noted below.

• Spanish flu – 1918-1919, killed 50 million people.
• Asian flu – 1957-1958, killed 1.1 million.
• Hong Kong flu – 1968, killed 1 million.
• Swine flu – 2009, killed 18,500.
• HIV – Occasional cases from 1959 to 1977, with an epidemic starting in 1981. A total of 75 million have been infected, and 32 million have died. About 38 million currently infected.
Ebola – 1976, with recurrences, including in 2014-2016, 2017, and 2018.
• Dengue – Eradicated in 1962 but returned in 2010, with recurrences.
• Zika – 2013-2014, with recurrences.
• Chikungunya – Periodic outbreaks since 1952, with increasingly frequent recurrences.
• SARS-CoV – Severe Acute Respiratory Syndrome Coronavirus, 2002-2003, fatality rate of 10 percent, with 774 deaths in 27 countries.
• MERS-CoV – Middle East Respiratory Syndrome Coronavirus, 2012, fatality rate of 35 percent, with 842 dead. It is in 10 countries and is recurring.
COVID-19, 2019-nCoV, SARS-CoV-2 – Coronavirus disease 2019. As of March 15, 2020, it had reached 140 countries, infected 163,418 people, and killed 6,086. The fatality rate is less than 3.7 percent.

As a rule, the initial incubation of viral diseases is due to factors like climate change, urbanization, and the juxtaposition of wildlife against humans and their domesticated animals. Subsequent infections result especially from air travel, with spread of the virus mainly by aerosol droplets. Since both of these stages require a high density of hosts, emerging viral diseases are actually diseases of overpopulation. If the Asia-Pacific region has become one of the world’s early foci for the emergence of new RNA viruses, this is because of crowding and rapid expansion, together with routine air travel.

Most of the pathogenic viruses we know about move through non-humans before they infect humans. Furthermore, these viruses evolve as they jump from one animal to another. So to them, we are just another host species on their quest to evolve. The non-humans initially used by pathogenic viruses are regarded as their “reservoirs.” These animals include farmed as well as wild mammals and birds, plus arthropods including ticks, spiders, and mosquitoes. The so-called reservoir animals are not sick, and it is completely normal that they should host a microbial fauna different from ours. This appears to be one of Nature’s ways to make sure species stay in their place. Poultry, for example, frequently carry influenza strains without any harm to themselves, and they have been sources of many flu outbreaks damaging to humans.

With regard to coronaviruses, it is bats that are most worrisome, because they host the greatest variety of such viruses. SARS-CoV probably jumped to humans from healthy masked palm civets and raccoon dogs that had been exposed to bats and were sold in Chinese wildlife markets. MERS-CoV infected people who rode, drank the milk, or ate the flesh of healthy camels that had come into contact with bats.

The threat from coronaviruses is that they can potentially infect, not only the respiratory system, but also the gastrointestinal, hepatic, and central nervous systems of humans. Usually the virus cannot infect all those tissues unless the host is in some way impaired, either by age, health problems, or simultaneous infections. Coronaviruses can also cause disease and death in some livestock, bird, bat, mice, and many wild animal species. The individual viruses differ, however, in their host preference.

Currently there are four identified types of pathogenic coronaviruses: alpha, beta, gamma, and delta. So far, only the alpha and beta have caused infections on humans. The general public may be aware of SARS, MERS, and COVID-19, which have killed about 165,000 people since 2002. All three of these are caused by beta-coronaviruses. At least four other coronaviruses have infected humans: Human CoV-OC43 and Human CoV-HKU1 are both beta-coronaviruses but less harmful than the three most of us know about; OC43 causes mild respiratory infections, and HKU1 causes pneumonia but not death. Human CoV-229E and Human CoV-NL63 are alpha-coronaviruses that cause mild respiratory tract infections, and they have been regarded, more or less, as agents of the common cold.

Other alpha- and beta-coronaviruses have caused massive fatalities or serious diarrheas in pigs, cats, cows, horses, and mice. Gamma viruses, for their part, have caused serious to fatal illnesses in Beluga whales and chickens. Delta viruses have been especially lethal to some wild bird species, including sparrows. Our efforts to understand and conquer coronaviruses have mainly been motivated by the urgency to fight infections of humans and livestock. This is probably a time for us to become alarmed when sparrows die of an infection and learn to treat it with equal concern.

The different types of pathogenic coronaviruses (alpha, beta, gamma, and delta) are only about 54 percent identical in sequence, which is not much. Even if we compare the agents of SARS and COVID-19, both of them beta-coronaviruses, their genomes are only about 80 percent identical. Again, this is not much resemblance. But there exist coronaviruses in bats that have better than 90 percent sequence identity to the agent of COVID-19, and a coronavirus from pangolins with 99 percent identity to the virus from COVID-19 patients. So the current thought is that the COVID-19 virus may have jumped from a bat to a pangolin, before it moved on to humans.

Coronaviruses are the biggest RNA viruses known, with a genome of about 30,000 nucleotide bases. Their genome is a positive single-stranded (+ss) RNA that is all ready to go when they infect a cell. Remember that pathogenic viruses are parasites. It is the host cell, by that I mean our own system, that reads the viral RNA as if it is its own and initially translates it into protein. The first proteins made are two very large proteins that have to get resolved into smaller parts so that the whole thing may work as a massive complex. Next, it is also the infected host cell that provides most of the enzymes to cut these large viral proteins into smaller working parts. The resulting complex of about 16 viral proteins now becomes a kind of machine that sets up the virus to evade the host’s immune system, as well as manufacture all essential components for the assembly of future viruses. These include at least four more proteins that become part of the viral structure, and ultimately its (+ss) RNA again, so it can make many more of itself.

Compared to SARS, the agent of COVID-19 appears to have two proteins that are new. Among the structural proteins, the spike protein, also called the S-protein, on the COVID-19 virus’ surface is the one that most interests scientists. The external part of this spike protein is only 40 percent identical to the one in SARS. This is important, because the external part of the spike protein is the part that recognizes human cells. The spike in COVID-19 binds to a protein on human cells called angiotensin-converting enzyme 2 (ACE-2), prior to infection.

In principle, one should be able to design a small-molecule drug that binds to the spike and prevents it from attaching itself to the human ACE-2 protein. Alternatively, one could administer the distinctive portion of the spike to people as a vaccine. In practice, however, these approaches are extremely difficult with RNA viruses. The virus of COVID-19, like all other coronaviruses, replicates its genome using an error-prone enzyme: a reverse transcriptase that makes an average of about 3 mistakes in every new virus it makes. In the face of any kind of pressure, the virus with the most fortuitous mistakes rapidly dominates a population. There is no vaccine against coronaviruses or any small-molecule drug that can stop them, even though scientists have been trying to develop these since SARS first appeared 18 years ago. Various promising drugs have been developed, but they have generally failed in clinical trials. However, there are new approaches for diagnosis and treatment of COVID-19 in the works. These will be discussed in my upcoming article on solutions for COVID-19.

Editor’s Notes: Dr. Dady Chery is an Associate Professor of Biology, Co-Editor-In-Chief of News Junkie Post, and the author of We Have Dared to Be Free: Haiti’s Struggle Against Occupation. Photographs one, eight and eleven from the NIH (National Institute of Health) archive; photograph four by Carnavoda; photograph six by Almasudi; and photograph twelve from The National Guard archive.

Listen to an interview with Dr. Dady Chery on March 17, 2020 in the following segment.

Listen to “Dr. Dady Chery on Coronavirus and Its Spread” on Spreaker.

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