Algorithm for creating a new type of antiviral drugs

Create a fake cell to inactivate respiratory viruses.

Compared to the wide range of antibacterial drugs, the spectrum of antiviral drugs is very small. This happens for two reasons. The first is the high mutation rate of viruses, which allows them to evade developed drugs. The second is intracellular reproduction and the peculiarities of the functioning of viruses inside the cell, which complicate the effect of drugs on them. [1]

These features can be called the strengths of a viral infection. And at the same time, this is their weak point.

To penetrate into the cell, the virus must interact with the surface structures of the cell. These structures are stable, which means that the components of the virus interacting with them must also be stable. And this is the Achilles' heel of viruses, despite the speed of their mutations. This is the first constant that could help create a new class of antiviral drugs. [2]

The elusiveness of the virus inside the cell is the second traditional obstacle to the creation of antiviral drugs. But at the current level of development of biotechnology, it also turns into the Achilles heel of viruses. For reproduction, the virus needs cell structures - organelles, genome, special molecules. No cell - no virus multiplication. [3]

Based on these features of the life cycle of viruses, in January 2020, a schematic diagram of the creation of a new class of antiviral drugs was proposed and published in Russian [4].

The essence of this principle is the creation of a phospholipid bubble - a fake cell with receptors attached to the surface of the sphere, to which the virus attaches and begins the process of penetration into the cell.

Once in a fake cell, the virus begins to prepare for reproduction, loses its shell, etc. If the fake cell is filled with cleaving enzymes, then the structures of the virus are immediately subjected to cleavage. If the sphere is filled with an inert substance, then the fake cell becomes a mousetrap for viruses that cannot multiply, because there are no cell structures and molecules necessary for this.

In February, this scheme was translated into English, published [5], and sent to several laboratories. Specifically, a letter was sent (and received) to Professor Robert Langer (Scientific Advisory Board Robert Langer, Sc.D. Cellics Therapeutics, Inc. (Cellics)).

Cellics 10 years ago created a kind of fake cells - nano-sponges and tried to use them for traditional purposes - as an enterosorbent for bacteria and toxins.

Based on the scheme proposed in a letter to Professor Robert Langer, a group of scientists from the University of California San Diego and Boston University School of Medicine have created nano-sponges with angiotensin converting enzyme 2 (ACE2) and CD147, placed on the surface of nano-sponges and acting as receptors for the entry of SARS-CoV-2 into the cell. [6]

Thus, the first functioning fake cell was created with virus receptors on its surface.

The effectiveness of this concept has been tested in vitro [7].

In laboratory experiments with nano-sponges covered with membranes such as lung and immune cells, it was found that the causative agent of COVID-19, the SARS-CoV-2 virus, has lost almost 90% of its activity. [7]

On June 17, 2020, articles [6,7] were published, signed, including by Liangfang Zhang, founder of Cellics (Liangfang Zhang, Ph.D., Founder Cellics Therapeutics, Inc. (Cellics)) describing the implementation of the proposed to professor Robert Langer. Nano-sponges in this development performed the function of a pseudo-cell, and angiotensin-converting enzyme 2 (ACE2) and CD147, placed on the surface of the nano-sponges, allowed the SARS-CoV-2 virus to penetrate inside this fake cell.

Thus, a fundamentally new application for nano-sponges was found and the efficiency of the proposed [4,5] scheme for creating antiviral drugs was tested.

This makes it possible to start the development and creation of a fundamentally new type of antiviral drugs in many pharmaceutical companies around the world.

Possible areas of application of the scheme fake cell + receptor and options for improving this scheme.

In addition to receptors for SARS-CoV-2, on the surface of nano-sponges, according to the proposed scheme [4,5], it is possible to place molecular structures used by other respiratory viruses (adenovirus, etc.) to penetrate the cells of the body. In addition to respiratory viruses, the proposed receptor + fake cell scheme can be used to create antiviral drugs against viruses that use blood cells (HIV, etc.) and gastrointestinal epithelium (rotavirus, etc.) for multiplication.

In addition, the scheme for creating a new class of antiviral drugs can be improved by modernizing the fake cell itself.

You don't need to use nano-sponges, or otherwise create a phospholipid vesicle or fake cell. A portion of the cell membrane and receptor is enough to trigger the deception and deactivation of the virus. [4]

Having established contact with the receptor, the virus starts a cascade of reactions leading to its unpacking and, in the conditions of the cell, ending with the creation of new viral particles. But this requires a real cage. Reproduction of the virus will not occur in a fake cell without organelles and the genome of the macroorganism, will not occur in the lumens of the bloodstream, gastrointestinal tract, alveoli and bronchi.

This means that you can create a drug that mimics only a part of the membrane + the receptor. This will lead to the unpacking of the viral particle and the release of genetic material into the void (into the bloodstream, into the lumen of the gastrointestinal tract, alveoli or bronchi), where the virus cannot multiply, and its molecules will be destroyed.

But you can also get rid of such components of the drug as fake cell or fake membrane.

To penetrate a cell, the virus does not use the entire structure of the receptor, not the entire complex of molecules covering the cell, but only a small part of them. So, on the basis of the proposed [4,5] principle, it will be possible to create a medicine containing only a significant part of the receptor on a substrate inert for the body. This will reduce the cost of creating and producing the drug and the final price for the consumer, as well as reducing the risk of unwanted side effects, for example, allergic reactions.

Of course, different viruses use different mechanisms to enter the cell. But the weak points are the same for all - the need to selectively attach to the cell and the need for the presence of cell structures and molecules for the reproduction process. [2,3]

Conclusions.

Three proposed options: receptor + fake cell [4,5], receptor + membrane fragment [4], part of the receptor + inert substrate, will help in creating a wide range of antiviral drugs.

References

1. Bobkova M. R. Drug resistance of HIV. M.: Chelovek, 2014. p 288]

2. Pinevich A. V., Sirotkin A. K., Gavrilova O. V., Potekhin A. A. Virusologiya Virology. SPb. «Izd-vo Sankt–Peterburgskogo universiteta» 2020, p 442

3. Medical microbiology, virology, immunology. Textbook in 2 volumes. Pod red. Zvereva V.V., Boychenko M.N. GEOTAR-Media 2019. p 472]

4. Sokolov A.L. Virus Trap. https://gabr.org/teorii/antivirus.htm (27 Jan. 2020).

5. Sokolov A. Creating a new class of antiviral drugs. https://gabr.org/teorii/antiviral_drugs.htm (10 Feb 2020).

6. Qiangzhe Zhang, Jiarong Zhou, Hua Gong, Ronnie H. Fang, Weiwei Gao, Liangfang Zhang, Anna N. Honko, Sierra N. Downs, Jhonatan Henao Vasquez, Anthony Griffiths. Nano-sponges for deception SARS-CoV-2. The virus recognizes the nano-sponges as a cell and combines with them. As a result, it does not reach a real cell and loses its ability to reproduce. // UC San Diego News Center https://ucsdnews.ucsd.edu/pressrelease/nanosponges-2020 ( 17 June, 2020).

7. Qiangzhe Zhang, Anna Honko, Jiarong Zhou, Hua Gong, Sierra N. Downs, Jhonatan Henao Vasquez, Ronnie H. Fang, Weiwei Gao, Anthony Griffiths, Liangfang Zhangcorresponding. Cellular Nanosponges Inhibit SARS-CoV-2 Infectivity. // The Journal Nano Letters. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301960/ (17 June, 2020).

Correspondence and requests for materials should be addressed to Dr. Andrey Sokolov 2336694@gmail.com

Keywords: Virus, drug, COVID-19, SARS-CoV-2, antiviral drug, respiratory virus, nano-sponges, fake cell, receptor.

Abstract. The article describes a schematic diagram of the creation of a new class of antiviral drugs. An example of an experiment confirming the performance and technical feasibility of the proposed scheme is given.

The proposed scheme makes it possible to turn the minuses of viruses (high mutation rate and intracellular reproduction) into pluses for the creation of effective antiviral drugs.

A fundamentally new approach to the creation of antiviral drugs using fake cells, nano-sponges and receptors on an inert substrate or fragments of cell membranes makes it possible to create a wide range of effective antiviral drugs.

The scheme is proposed to create antiviral drugs for respiratory viruses and viruses that use blood cells and gastrointestinal epithelium for multiplication.