**1. Introduction**

The objectives of this introductory chapter is to outline the possible intervention therapeutic strategies against SARS-CoV-2.

Upon such vision, all research projects, scientific creations, trouble-shooting and problem-solving techniques must be based on healthy environment. As a matter of fact, the environment has provided us with the best of everything, of food, water, air, and a cure for every illness. In our turn, we should make good use of God's blessings bestowed upon us through natural sources by which we can fight contagious diseases including COVID-19.

Accordingly, the founding factors of this vision will be:


The premises of this vision are:


### **2. A possible approach for intervention of SARS-CoV-2 infectivity**

SARS-CoV-2 genomic RNA is protected by two envelopes: phospholipid bilayer and protein. The human cell entry by the virus was prompted upon S-protein (Spike protein), which resides in the envelope anchors to ACE2. Protease cleaved the S-protein into S-1 and S-2 fragments, whereas S-1 binds to ACE2. While S-2 was cleaved by serine protease enzyme (TMPRSS2), leading to membrane fusion. This may halt the first step of infection with the virus, as presented in **Figure 1**.

#### **Figure 1.**

*SARS-CoV-2 entry to the host cell (airway cell) that initiates with the S-protein on its envelope and the endocytosis process. This illustrates the essentiality of ACE2 and TMPRSS2 in the SARS-CoV-2 infection.*

#### **3. Promising natural serine protease inhibitors**

Serine proteases, including elastase, trypsin, and chymotrypsin, are a large class of enzymes and play various roles in human health, including blood coagulation and immune response. An increase or decrease in protease activity can induce pathologies, including inflammation, cancer, stroke, heart attack, and pancreatitis.

#### **3.1 Halting of viral replication**

#### *3.1.1 Inhibition of SARS-CoV-2 NSP15 endoribonuclease*

Nidoviral RNA uridylate-specific endoribonuclease (NendoU) is one of the enigmatic enzymes that is corresponding to Nsp15, carrying a C-terminal catalytic domain (EndoU family). They perform various biological functions related to RNA processing. All characterized family members display an RNA endonuclease activity [1].

Inhaled ciclesonide is expected to reduce viral replication and host inflammation in the lungs, with decreased immunosuppressive effects compared to systemic corticosteroids, as ciclesonide primarily remains in the lung tissue, and does not significantly enter the bloodstream. This is also considered to be another example of drug repurposing. Therefore, we could conclude that natural steroids are potential inhibitors [2].

*3.1.2 SARS-CoV-2 main protease inhibitors (Mpro = 3CLpro)*

There are many examples of α-keto amides inhibitors of natural origin, such as eurystatin A and B (prolyl endopeptidase inhibitor), complestatin (HIV replication inhibitor), and aplidine (antitumor) (**Figure 2**) [3].

*Introductory Chapter: An Intervention Therapeutic Strategies against SARS-CoV-2 DOI: http://dx.doi.org/10.5772/intechopen.106415*
