viruses make mistakes — that is, they introduce wrong nucleotides, leading to mutations. The large CoV-2 genomes could accumulate too many mistakes and die out. This is prevented by a correction system, a “viral proof-reading”, to eliminate mistakes. This leads to a genome stabler than that of many other viruses. Mistakes, meaning mutations, are normally a means by which a virus evades the immune system of the host, escaping by making rapid changes. Mutations of CoV-2 have been observed, as expected, with numerous viral isolates being sequenced. Some of them are leading to a much higher pathogenicity. Problems for vaccines will have to be determined.
Another approach is already under investigation. It was tried during an Ebola virus outbreak on an American who returned to the USA infected by this deadly virus, of which more than 90% of infected people do not survive. The survivors are carriers of antibodies, and these were isolated from their blood in an attempt to cure newly infected people. The patient survived. This approach is being used with the antibodies of COVID-19 survivors. It cannot save the whole world.
The efforts to develop vaccines or drugs have activated hundreds of researchers in many fields: virologists, molecular biologists, biochemists, chemists, geneticists, molecular designers and bioinformatics specialists. This is going to be exciting. Start-up companies are usually innovative and original. Then the big pharmaceutical companies will need to step in. They will have to drive the approach to the market, which requires more resources than small start-up companies have. We will need highly up-scaled production for worldwide supplies and distribution. This will take time, however.
We need an immediate intermediate solution.
Therapeutics
Therapeutics against viruses have not been too successful in the past. One such example is influenza virus, against which the number of drugs is very limited. An unusual exception is HIV, against which more than 30 drugs are available. They are taken in triplet combinations which, to this day, have turned out to be extremely successful. Three drugs against different molecular targets, blocking different steps in the life cycle of HIV, prevent the development of drug resistance. This approach has been adopted for other diseases as well, including cancer, where drug-resistant cells also arise quite rapidly.
Coronaviruses do not mutate so rapidly, but here also more than one drug will be required.
A favorite target for antiviral drugs is the virus’s protease enzyme. Many viruses have such an enzyme to trim their proteins, which are often synthesized in large pieces. The viruses need their own proteases so that no confusion can occur with cellular proteases. Protease inhibitors against SARS have been made, and a sculpture of the protease against SARS is on exposition in Singapore with a protease inhibitor bound to it. This will soon be designed accordingly against CoV-2. A protease inhibitor was also successful against HIV. Hundreds of different drugs are under investigation around the world against CoV-2. It would be fastest if a drug could be redirected to this new disease, and tested rapidly such as drugs against Ebola, HIV, malaria and others. This would speed up the process for rapid applications. Furthermore, in several cases, nucleotide analogues have proved useful as inhibitors; their incorporation into the progeny RNA leads to its destruction. However, the CoV-2 repair system may perhaps prevent this. Many drugs are under investigation and more are coming, almost daily.
Interestingly, some drugs may help save lives which are directed against secondary complications not the virus itself, such as anticoagulants or drugs against hyperimmune responses, and may reduce the sometimes harmfully long respirator periods.
Viruses — more friends than foes?
Why is a chapter on the new pandemic virus SARS-CoV-2 part of a book on viruses which is not focusing on viral diseases but is dedicated to our understanding of the importance and positive roles of viruses for our world, our environment, our evolution, and their contribution to innovation and composition of our genes — which are almost half of viral origin. Viruses entered our genomes in the past as a protection against de novo infections and they protect embryos against a mother’s immune response. There is an intimate coexistence, a balance between microorganisms and humans, animals and plants. We are a unity and an ecosystem. Microorganisms have been around on our planet for so long and we are the newcomers. The microorganisms, including bacteria and their viruses, are necessary for our existence, we even depend on them for our survival. They help us to digest food in our guts, to cope with our surrounding, and they recycle the food chains in the oceans. Viruses of bacteria, the phages, clean up seasonal overgrowth of bacteria in the oceans.
We humans entered the scene very late and we still need to learn how to cooperate with the world.
The well-balanced ecosystem is complex and can get out of control — and this we have to blame predominantly ourselves. The causes are often wars, poverty, hunger, lack of hygiene, or ruthlessness against nature. Simple common denominators of all these occurrences are population density and mobility. We may not be able to change that in the near future or we may not even want to. That has its price. And we are presently paying for it.
In the chapters of this book the reader is invited to travel with me through the astounding world of viruses, which do not cause diseases.
2 Viruses — not as you pictured them
Viruses — a success story
The word “virus” often provokes disgust: “Ugh, keep that out of here” — or “Watch out, they’re contagious, they make you ill”! Yet here comes a book about the opposite: Viruses are better than their reputation. Much better. This is a surprising reverse side of the viruses, which will be the topic of this book. Viruses as friends, not foes!
Everything in virology is new. Unnoticed, a paradigm shift has taken place: the focus is no longer upon diseases, but rather on the positive side of viruses: viruses as drivers of evolution, viruses leading to innovation, viruses at the origin of life — or at least their presence from the very beginning. Throughout evolution viruses have been our “bodybuilders” or gene modulators. What is a virus? Where do viruses come from? Are they alive or not? Why and when do they make us ill? Whether you, the reader, want to continue swimming in the sea — whether babies’ dummies from the Far East may cause cancer and should be avoided — whether you should stop enjoying salad because of the many plant viruses — these are questions that you can decide upon for yourself after having read this book.
While reading it, you will learn something about life — the innermost parts of your cells and your genes; you will find out how viruses contribute to our adaptation to environmental conditions; you will be confronted with the question of whether they may contribute to human free will; you will discover the extent to which we are related to bacteria and worms, and how sex can be replaced by viruses; you will find out that viruses “invented” all immune systems and supplied cells with antiviral defense mechanisms. This is much easier to understand than you may expect, and it reflects my own thinking. What part do viruses play in cancer development and gene therapy? Do “jumping genes”, which are “locked-in viruses”, create geniuses? Do you know that viruses can “see”? Almost they do, the color blue! You will read about efforts to save chestnut trees, about where stripes on tulips and the white patterns on blue balcony petunias come from (viruses of course) and how viruses caused the first financial crisis, known as “tulipomania”. Finally, one-third of mankind may want to know how to control body mass or obesity. (By viruses? Yes, indeed.) The viruses have contributed, and are still contributing, to all of these. And now, let’s start by reading about the success story of the viruses.
HIV particles aligned at the cell surface, electron microscopic picture.