Table 1 presents the results of the molecules related to 3CL-protease. A part of these molecules is proposed and used. These scores were obtained from our modeling model and represent the relative binding affinity.

Table (1):
The docking score of molecules and the active site of Protease.

Lopinavir had the highest binding affinity score, followed respectively by Azithromycin, Oseltamivir, Hydroxychloroquine, Tipranavir, Chloroquine, Nitazoxanide, AG70088, Remsidivir Zanamivir, Nelfinavir, Saquinavir and lastly Favipiravir.

Through our methodological investigation on the analysis of the interactions between different molecules and the active site of the protease, we were able to reveal the sites of interaction between the different compounds and the residues involved in this interaction (Fig. 1). Through our structural interpretation and visualization of the different interactions, we have found that the amino acid Glycine 189 is the common element of the interaction of those treatments, which may be considered further to elucidate this result.

The characteristic of this interaction is the high polarity between Lopinavir and the active site of the Protease.

An interesting exploration, Azithromycin well-known for its anti-bacterial activity, showed an interesting result with a relatively high score compared to the rest of the treatments, hence it is interesting to investigate its clinical results. This interaction is characterized by a higher number of amino acids (Fig. 2).

Oseltamivir as the first neuraminidase inhibitor available orally, classified in the third position with scores very close-to hydroxychloroquine, thus the interaction with the Protease is essentially with its N radical (Fig. 3).

Chloroquine and its derivative have the same classification with an approximately identical score with hydrogen interactions. However, hydroxychloroquine seemed to be more effective than chloroquine (Fig. 4).

The lowest scores were observed for Sequinavir and Favipiravir respectively. It was also observed that Favipiravir had the lowest number of amino acids generated in this interaction (Fig. 5).

In the following table we provide the 3-dimensional interaction of the molecules that are not included in the therapeutic strategies proposed, although they might be used as therapeutic alternatives (Table 2).

Table (2):
3D illustration of interaction of molecules including antivirals drugs and peptidomimetic agent.

Molecules	3D Illustration
TIPRANAVIR
AG7088
REMDESIVIR
ZANAMIVIR
NELFINAVIR
SAQUINAVIR

Remaining objective, our results demonstrate solely the scores that we were able to demonstrate based on our modeling methodology. That means that our results do not influence the favoritism of one treatment over the others. The treatments we have investigated in the manuscript are typically the subject of several clinical trials. Although our study is like the first trial, comparing the different treatments.

Hydroxychloroquine was reported to be of better affinity compared to Chloroquine⁸. These treatments are being proposed as a treatment for Covid19 and the clinical trials that may determine the effectiveness of these treatments are currently in progress^9,10.

It has been suggested that the therapeutic effect of lopinavir on SARS-CoV2 may be primarily due to their inhibitory effect on endopeptidase¹¹. Oral treatment with oseltamivir has been used as an empirical drug for several cases of SARS-CoV2 in Chinese hospitals¹². Another analysis comparing only antiviral agents had mentioned their efficacy on the modeling level, this Screening has studied 61 molecules, Lopinavir binds to all SARS-CoV2 protein structures with a docking score less than -6.5. Also, it is interesting to note that HIV protease inhibitors have shown strong results in silico docking¹³.

A briefing in China reported that chloroquine has been used successfully to treat more than 100 SARS-CoV2 infected cases resulting in improved radiological findings and viral clearance, and reduced disease progression. The score we obtained throughout our docking can be explained by the indirect action on the virus, although the proposed mechanism for chloroquine and hydroxychloquine Increases endosomal and liposomal pH required for virus/cell fusion⁹.

All of our results provide an overview of the prescription and repositioning of the different treatments cited in the literature. It is important to notice that the benefit-risk ratio and the therapeutic tolerance range should be taken into consideration.

The azithromycin seems to have an inhibitive effect on viral replication, given its broad spectrum of activity. The documents mentioning azithromycin report that it only may be used in association with other treatments, whereby, based on our analysis, the second classified azithromycin would be considered as a treatment with adaptations according to its pharmacokinetic parameters. Oseltamivir is being used in several clinical trials as a comparison group; the reasons for this are not unraveled except its effectiveness against influenza. A recently published In silico research demonstrated that Oseltamivir may have an inhibitory effect on the SARS Cov2 main protease¹².

There are limited trials investigating the antiviral activity against SARS Cov2 of the agents listed in Table 2. Concerning tipranaivir nonpeptidic protease inhibitor used in combination with ritonavir and demonstrated beneficial effect against HIV¹⁴. It was reported that nitazoxanide, through preventing membrane fusion and acting as an antiprotozoal agent, may have an inhibitory activity against COVID-19¹⁵. Zanamivir is an approved medication for the treatment of influenza A and B viruses¹⁶. Indinavir and Saquinavir have been shown to treat and prevent HIV. Remdesivir inhibits viral replication by initiating effective metabolic conversion in cells to activate nucleoside triphosphate which, in turn, inactivates viral RNA polymerases¹⁷. This agent has shown promising antiviral activity In-Vitro and is accessed for activity against SARS-CoV-2¹⁸.