The indiscriminate use of antimicrobial agents has led to the emergence of a number of
drug-resistant bacteria, fungi and viruses. To overcome the increasing resistance of
pathogenic microbes, more effective antimicrobial agents with new modes of action must be
developed.

Medicinal plants used in traditional medicines to treat infectious diseases are an
abundant source of new bioactive secondary metabolites. Therefore, in the last few years,
various medicinal plants and plant extracts have been screened for their antimicrobial
activities . Essential oils obtained from aromatic medicinal plants (e.g. fennel
(Foeniculum vulgare), mint (Mentha piperita), thyme (Thymus vulgaris)) have been shown to
have antimicrobial activity against gram-positive and gram-negative bacteria as well as
yeasts, It has been reported to be active against fungi and viruses. They are mixtures of
different lipophilic and volatile substances such as monoterpenes, sesquiterpenes and/or
phenylpropanoids and have a pleasant odour. They are also part of the pre-formed defence
system of higher plants are thought to be . Monoterpenes have been widely studied,
especially for their antiviral properties.

Nowadays, the use of essential oils is becoming increasingly widespread both in
pharmacies and in various stores. The use of essential oils for therapeutic purposes is
expanding. The molecules that make up certain essential oils have shown various antiviral
properties:

- Either by neutralising the virus before it enters the cell,

- By changing the capsid or envelope of the virus,

- Either by binding to receptors used by viruses and preventing their access to cells.

Herbal products are an important source of herbal remedies and other medicines. Essential
oils have shown various pharmacological activities, such as antiviral activity, and have
therefore been implicated in SARS-CoV- It has been suggested to have potential activity
against 2. Essential oils can easily penetrate the viral membrane due to their
lipophilicity and can cause rupture of the viral membrane.

In addition, crude essential oils often have many active components that can act on
different parts of the virus, including cell entry, translation, transcription and
assembly. Anti-inflammatory, immune regulation on the respiratory system of the host,
have other beneficial pharmacological effects, including bronchiectasis and mucolytics.

Essential oils have many advantages because they promise volatile antiviral molecules,
making them useful either alone or in combination with other chemotherapeutic drugs,
making them potential drug targets for the prevention and treatment of COVID-19.

In this study, a computational simulation approach of the molecular interaction (binding)
of the main components of essential oils exhibiting antiviral activity with known
intracellular protein targets of SARS-CoV-2 (nsp5: Master Protease) was adopted as a
rationale. A single-chain.

The RNA virus SARS-CoV-2 has four main structural proteins Spike (S), Membrane (M),
Envelope glycoprotein (E) and Nucleoapsid (N) proteins and non-structural proteins (nsp)
.

These non-structural proteins, of which there are 16 in total in the genome of the virus,
play a key role in the mechanisms of the virus life cycle, including replication,
transcription, protein synthesis and modification of RNA. Main protease (Mpro, 3CLpro)
has been the target enzyme for the development of new antiviral drugs for the treatment
of COVID-19 , as they are directly involved in the maturation of these nsp proteins,
which have an important role in many mechanisms of the virus life cycle. Our main
rationale in this study is to investigate the effect of essential oils on nsp5: Main
Protease enzyme activations.