Sirtuins, a possible alternative to counteract Covid-19

Dr. Marco Antonio Hernández Bedolla

L.E. Dulce Edith Alonzo Alonso

Student Abizai Herrera Hernández

Student Zaida Burgos Ostoa

*Research Group in Cellular and Molecular Biomedicine and Bachelor's Degree in Nursing at the Escuela Superior de Huejutla-UAEH.

The health crisis we are experiencing due to the pandemic caused by the SARS-CoV-2 (Covid-19) virus has led science around the world to seek knowledge of the biology of the virus inside the human body, which will allow the discovery of diagnostic and treatment alternatives for its control.

Our organism has an extensive range of molecules that allow it to maintain its functioning in optimal conditions, but if there is an imbalance in quantity or genetic dysfunctions, they become important factors for the development of diseases.

An example of this group of molecules are the sirtuins, a family of proteins that have the capacity to choose and cut part of an amino acid.

There are different types of proteins, some of which are identified as enzymes because they have the function of catalysts, i.e. they accelerate the speed of the chemical reaction of the substrate or molecule they modify.

In diseases such as Human Immunodeficiency Virus (HIV), influenza type A (H1N1), dengue, hepatitis, papilloma, herpes or other diseases affecting the respiratory system, sirtuin proteins or enzymes act as inhibitors of viral multiplication (replication), leaving them as tools for diagnosis or even for treatment.

Scientific research is divided into two, basic science and applied science. The latter depends on the advances and achievements of the former. Scientists working at the molecular level, i.e. doing basic science, when they manage to identify properties or characteristics of a protein under study, to mention an example, this knowledge can be used for therapeutic purposes.

In the case of sirtuins, their properties may represent a possible alternative to counteract COVID-19.

The research group in Cellular and Molecular Biomedicine of the Escuela Superior de Huejutla, with the participation of Dr. Alma Barajas Espinosa, Dr. Fernando Ochoa Cortés and myself, Marco Antonio Hernández, made a scientific review to explain what sirtuins are and where they come from, explain how they act in the organism, both in normal situations and the role they play in the development of diseases.

This information was published in the Scientific Bulletin "Ciencia Huasteca" of the Escuela Superior de Huejutla, of the Universidad Autónoma del Estado de Hidalgo, where also participated students of the degree in Nursing; which can be consulted in the following link:
https://repository.uaeh.edu.mx/revistas/index.php/huejutla/article/view/5721/7048

SIRTUINS IN YEAST, THE ORIGIN OF THE

The first sirtuin discovered was yeast SIR2. In the 1990's, genetic studies showed that this gene is important in the regulation of replicative life expectancy in yeast, i.e. it regulates their longevity.

Yeast is a microorganism widely used in the food industry to ferment, for example, beer or bread. If SIR2 is present in this yeast, it serves to prolong the life or multiplication of the microorganism.

SIRTUINS IN MAMMALS

After discovering sirtuin proteins in yeast, scientists identified them in different mammalian species, then named it as SIRT.

In this case, they discovered that there are seven variants that act differently depending on where they are located in the organism at the cellular level. The most interesting thing is that their location allows them to exert different functions.

The main one that has been studied is the control of aging, since it regulates physiological resilience, i.e. the mechanism that the cell, as a living system, has to favor its growth, maturation and death.

However, several studies show that each of the sirtuins has specific functions within the normal functional process of the body, such as aging, DNA (deoxyribonucleic acid) repair, gene silencing, stress response, metabolism, apoptosis (programmed cell death) and cell survival.

All of the above reflects the importance of sirtuins as key cellular orchestrators of the chemical balance known as homeostasis in humans.

SIRTUINS IN DISEASES

Human sirtuins play a substantial role in the pathological field, meaning that each one is involved in the development of different diseases such as inflammation, neurodegenerative diseases, cardiovascular diseases, insulin resistance, adiposity which is the accumulation of fatty tissue and cancer.

In basic research, especially in the health aspect, animal models are required, mainly mice that are bred in biotherapies. Thanks to these experiments, there are important advances in the discovery of how sirtuin proteins act in some diseases.

SIRTUINS AND VIRUSES

Nature has a variety of DNA or RNA (ribonucleic acid) viruses that infect specific human tissues or organs, resulting in major diseases such as hepatitis, papilloma, AIDS, dengue, herpes or respiratory system involvement, among others.

Sirtuins have a pleiotropic role, i.e. different functions that can influence positive or negative actions in humans. Science has shown that the seven mammalian sirtuins are antiviral factors.

In the last decade, researchers have studied the relationship of sirtuins with the functioning of viruses, where the results indicate that they are crucial in preventing the replication or multiplication of particles of some viruses, such as influenza type A (H1N1), adenovirus type 5, dengue virus, herpes simplex virus, hepatitis B and C, human papilloma virus (HPV) and acquired immunodeficiency virus (HIV).

Therefore, it is necessary to invest resources and focus research to help understand the role of sirtuins in the biology of SARS-CoV-2 and to position these enzymes as biomarkers for early diagnosis and as broad-spectrum antiviral candidates for the evolution of Covid-19.