A virus is not a living creature, but can be described as an assemblage that is a “pre-living thing” in the progression of evolution toward a living entity. It has a structure consisting almost of only a nuclear component, which has a DNA or RNA replication mechanism. Its outer surface is covered with a membrane called an “envelope,” which is composed of lipids and some glycoproteins. Lipid components of the membrane are soluble in alcohol; therefore, alcohol at a high concentration is effective for hand sanitization, along with soap and detergent. In these cases, the meaning of “effective” refers to the situation where a virus membrane can be dissolved with these materials. Although the DNA or RNA components remain undissolved, a virus is surrounded with abundant enzymes (DNases and RNases) that destroy them. Therefore, dissolution of the membrane may be tantamount to destruction of the virus itself.

The structure of a virus envelop is completely different from that of bacterial cell membrane. Bacterial cell membranes are composed of lipids and polysaccharides. Gram staining, invented by Dr. Hans Christian Gram, a Danish bacteriologist (1853–1938), enables us to roughly categorize bacteria into gram-positive and gram-negative species. The stain colors are different according to the membrane structures. E. coli, for example, is a gram-negative bacterium, while Staphylococcus aureus and Mycobacterium tuberculosis are gram-positive bacteria. The use of penicillin, a type of antibiotic, is closely related to these differences in color.

In any case, these foreign substances are “non-self” to humans. In the nasal mucosa, the respiratory system beginning with the oral cavity, and the digestive tract, various barriers obstruct these foreign substances and prevent them from entering the body. Once they enter the body, immunosurveillance initiates its response. Macrophages play the key roles to initiating this sequence of processes, which are a major component of innate immunity. When foreign substances enter the body, macrophages phagocytize them and present a large number of antigen fragments (epitopes) on their outer cell surface. This feature of macrophages is associated with “Senju-Kannon”, the Buddhist deity of mercy with one thousand arms having various kinds of presents (epitopes). Various antigen fragments are presented in her many hands to promote production of IgM-specific antibodies by helping with T and B lymphocytes. In the second attack of the same antigens, B lymphocytes proliferate and differentiate into plasma cells and secrete stronger, sharper, and highly specific IgG antibodies in any epitopes related to the same antigen attacks. This is the mechanism of acquired immunity. The IgG antibodies, which have the abilities to eliminate the same foreign bodies with help of serum complements called opsonin effect, are defined as complete antibodies and can be used for serum therapy. Based on this phenomenon, antigenic epitopes that can produce complete antibodies are expected to work as a certain specific vaccine. On the contrary, antigenic substances that produce incomplete antibodies are inappropriate as vaccine candidates, since they exert no opsonin effects. Therefore, there might be various obstacles to find complete antigenic epitopes in COVID-19 viral substances in a short time.

Antibiotics exert their effectiveness on major types of bacterial infections. Thanks to them, we can enjoy everyday life without fear of these life-threatening infections. There are no words to express the magnitude of the achievement by Alexander Fleming, who discovered penicillin and developed its production process using a blue mold variant as a raw material.

Penicillin can terminate the survival of gram-positive bacteria by decomposing the bacterial enzymes that are necessary for cell membrane formation. Who could have imagined that bacteria or fungi were fighting in the natural environment? Selman Abraham Waksman discovered streptomycin from actinomycetes in the soil, and called it an “antibiotic.” Dr. Hamao Umezawa, a Japanese researcher, was also known for his discovery of many useful antibiotics, among others, kanamycin. Research and development of antibiotics subsequently progressed, and vancomycin and methicillin, which also destroy gram-negative bacteria, were invented. However, bacteria sometimes retain mutated DNA and, as a result, sometimes change into antibiotic-resistant bacteria.

Antiviral drugs, on the other hand, are “nucleoside analog” drugs, which inhibit formation of viral DNA or RNA nucleotide sequences. These drugs are not considered to penetrate the cell membranes of bacteria, since bacterial nucleotide sequences are completely different from viral ones. Nucleoside analog drugs used for hepatitis C virus (an RNA virus) at present can be orally administered. This was almost unimaginable during the 20th century.

DNA viruses are generally less likely to mutate at their nucleotide sequences, while RNA viruses are prone to this type of mutation. Influenza virus is a type of RNA virus and likely to mutate. Tamiflu, an anti-influenza virus drug, inhibits an enzyme called neuraminidase, which is found in viral envelopes. Neuraminidase works to extracellularly release viruses that replicate in infected cells. Tamiflu is an early treatment for influenza virus infection and exerts its effectiveness by inhibiting this enzyme. Moreover, it is expected to prevent cellular infection by promoting virus cohesion. Avigan is also used as an anti-influenza virus drug.

COVID-19 is also a species of RNA virus similar to SARS and MERS. They are all corona-type viruses. Remdesivir, an anti-viral drug that is now under development, is a nucleoside analog drug designed to inhibit viral replication.

The tendency of RNA viruses to frequently mutate is troublesome. This characteristic makes it difficult for nucleotide analogues to block replication of virus nucleotide sequences. Additionally, because of this attribute, antigens tested in vaccine development are sometimes unstable. Therefore, there is a concern that administration of vaccines to humans may interfere with production of complete antibodies. In either case, antiviral drugs don’t work on bacteria, since the targets in viral and bacterial infections are different.