PROTEIN SIGNALING MOLECULES AFFECTING THE DEVELOPMENT OF INNATE IMMUNITY MECHANISMS

The principle protein molecules (interferon gene stimulator, adapter proteins, B-cell lymphoma 2 proteins, zinc-finger antiviral protein, and others), mechanisms of apoptosis, necroptosis, perforation of plasma membranes with kinase-like proteins of a mixed line, and ribonucleic acid neutralization, which ensure the development of innate immunity, are described. The main defense mechanisms that viruses have developed at the various stages of evolution are considered. The features of the development of the mechanisms of apoptosis and autophagy in a new coronavirus infection, which are associated with increased secretion of pro-inflammatory cytokines and chemokines, leading to severe damage to host cells, are given. It has been found that serum levels of several proteins formed during autophagy caused by SARS-CoV-2 can be used to predict disease severity. These include a protein associated with microtubules 1A/1B, a protein of sequestoma 1, and a protein of the cellular system of autophagy ― beclin-1. The multifaceted role of interferons in the inhibition of viral infection and the features of the violation of the activating functions of interferons in coronavirus infection are described. The article can be used under the CC BY-NC-ND 4.0 license © Authors, 2022.

Neutrophil-Lymphocyte Ratio Predicting Case Severity in SARS-CoV-2 Infection: A Review.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly contagious and has taken an enormous toll on the worldwide quality of life and the global economy, in addition to the lives lost due to coronavirus disease 2019 (COVID-19). Precautionary measures and timely identification of the infected cases are essential to minimize the spread of SARS-CoV-2. Infection with this virus causes a spike in the proinflammatory cytokines, resulting in immune system-mediated host tissue damage, thus leading to mortality. Therefore, identifying mild, moderate, and severe cases is crucial to rendering appropriate care. Recent research has focused on identifying laboratory techniques to predict the case severity and outcome of COVID-19 cases. Low serum lymphocyte levels, low lymphocyte-to-C-reactive protein ratio, low platelet-to-lymphocyte ratio, thrombocytopenia, and high neutrophil-lymphocyte ratio (NLR) have been observed in critical infections. NLR might be a prognostic marker for disease severity. Severe cases can be triaged at hospital admission for proper treatment planning and to reduce mortality. This review highlights the potential role of NLR hematological assay in SARS-CoV-2 infection and the mechanism of neutrophilic-induced host tissue damage.

Proteases of SARS Coronaviruses

Coronaviruses such as SARS and SARS-CoV-2 have established themselves as a global health concern after causing an epidemic and a pandemic in the last twenty years. Understanding the life cycle of such viruses is critical to reveal their pathogenic potential. As one of the essential viral enzymes, SARS proteases are indispensable for the processing of viral polypeptides and for the replication of the virus. SARS-CoV and SARS-CoV-2 encode for 2 viral proteases: the main protease (3CLpro) and the papain-like protease (PLPro), which are conserved among different coronaviruses and are absent in humans. This review summarizes the existing literature on the structure and function of these proteases;highlighting the similarity and differences between the enzymes of SARS and SARS-CoV-2. It also discusses the development of inhibitors to target viral proteases. © 2023 Elsevier Inc. All rights reserved.

Discovery of Novel Cysteine Protease Inhibitors for the Treatment of Coronavirus (COVID-19).

The application describes compounds, such as compounds of general Formula, with warheads and their use in treating medical diseases or disorders, such as viral infections. Pharmaceutical compositions and synthetic methods of various compounds with warheads are included. The compounds are inhibitors of proteases, such as the 3C, CL- or 3CL-like protease.

Anti-viral compounds from Jatropha curcas seed extract with anti-HIV-1 and anti-SARS-CoV-2 action

Many studies have dealt with the medicinal properties of Jatropha curcas;however, there are limited studies on the scope of its antiviral potential. This is a fact associated with the current challenges posed by HIV-AIDS and COVID-19, which has reinforced the need to expand the knowledge about its antiviral resource. Based on the search for natural products with anti-HIV-1 and anti-SARS-CoV-2 activities, this work analyzed the extract of J. curcas seed, the structure of the plant whose antiviral references were not found in the literature, and the compounds that can potentiate it as a candidate for herbal medicine. GC-MS analysis was used to screen for the active substances of the J. curcas seeds, and the literature was searched to find those with anti-HIV-1 and anti-SARS-CoV-2 indication. The results showed they have 27 compounds, of which glycerol 1-palmitate, stigmasterol and gamma-sitosterol were shown to have antiviral action in the literature. Regarding glycerol 1-palmitate, no detailed description of its antiviral action was found. Stigmasterol and gamma-sitosterol act as anti-HIV-1 and anti-SARS-CoV-2, respectively, inhibiting the reverse transcriptase of HIV-1, the proteases 3CLpro, PLpro and the spike proteins of SARS-CoV-2. However, despite the fact that the extract of J. curcas seeds consist of antiviral compounds that fight against the etiological agents of HIV-AIDS and COVID-19, it is concluded that there is a need to deepen this evidence, by in vitro and in vivo assays.

In-silico studies of active phytochemicals from siddha medicinal herbs of karisalai chooranam against SARS-CoV-2 main protease (3 CLpro), RNA dependent RNA polymerase and angiotensin-converting enzyme II receptor

Aim: The contagious disease COVID 19 is a recently out-broken pandemic situation which threatens humankind all over the world. Siddha system of medicine is one of the traditional medical systems of India, which has provided a novel remedy for many epidemics like Dengue, Chicken guinea earlier. On evaluating the literature evidence and considering the mortality and severity of the disease, we have attempted to identify the possible inhibition of viral replication by "Karisalai Chooranam" - a polyherbal Siddha formulation which contains herbs like Karisalai (Wedelia chinensis), Thoodhuvelai (Solanum trilobatum), Musumusukai (Melothria maderaspatana) and Seeragam (Cuminum cyminum). The aim of this study was to identify the bioactive components present in Karisalai chooranam and pin down the components that inhibit COVID 19 protease by In Silico molecular docking analysis. Material and methods: The study was performed for the active compounds present in the herbs (Wedelia chinensis - Benzoic acid, Solanum trilobatum- Disogenin, Melothria maderaspatana- beta-sitosterol, Cuminum cyminum L- Coumaric acid and Limonene) with three potential targets, PDB id: 6LU7 3-chymotrypsin-like protease (3CLpro), PDB id: 6-NUR RNA dependent RNA polymerase and PDB id: 2AJF Angiotensin-converting enzyme II (ACE2) receptor using Autodock Vina. Key findings: The active phytocomponents present in "Karisalai chooranam" was found to inhibit the target 3CL proenzyme and hereby halt the formation of 16 non-structural proteins (nsp1-nsp16) that are highly essential for viral replication and there by prevents viral survival in the host environment. The phytocomponents also inhibited the target RNA dependent RNA polymerase (PDB)-6NUR RdRp which possess versatile action in mediating nonstructural protein (nsp 12) essential for viral replication. A significant binding against the target Angiotensin-converting enzyme II (ACE2) receptors - PDB- 2AJF was found which was recognized as a binding site for novel coronavirus to cause its pathogenesis. Among the five active components present in the herb, the binding ability of Disogenin and beta-sitosterol with COVID19 protease suggests a possible mechanism of protease inhibition and thus preventing viral replication. Significance: The results strongly suggest that phytocomponents of "Karisalai chooranam" may act as a potential therapeutic agent for the management of COVID-19 and related symptoms. Further, the efficacy of the active compounds should be tested in vitro before being recommended as a drug.

Antiviral activitiy of curcumin, demethoxycurcumin, bisdemethoxycurcumin and cyclocurcumin compounds of Curcuma longa against NSP3 on SARS-CoV-2

SARS-CoV-2 genome encodes two large polyproteins (pp), pp1a and pp1ab which are cleaved and transformed into a mature form by a protease, non-structural protein 3 (NSP3). NSP3 is encoded by open reading frame (ORF) 1a/b. Curcuma longa (C. longa) or turmeric has been documented to have antiviral effects. The aim of this study was to assess the viral activities of C. longa against SARS-CoV-2 focusing on its potency to inhibit viral replication by targeting NSP3. PubChem databases were used to obtain the metabolic profile of C. longa. The compound's interaction with nucleocapsid was analyzed using molecular docking with Molegro Virtual Docker. Bioinformatics analysis based on rerank score presents all compounds of C. longa have higher binding affinity than the native ligand with cyclocurcumin as the lowest score (-128.38 kcal/mol). This anti-viral activity was hypothesized from the similarity of hydrogen bonds with amino acid residues Ser 128 and Asn 40 as key residues present in Ribavirin. This study reveals that C. longa is the potential to be developed as an antiviral agent through replication inhibition in SARS-CoV-2 targeting its replication mediated by NSP3.

Special issue on COVID. (Special issue on COVID.)

This special issue comprises 8 articles that explore various aspects of the COVID-19 pandemic from mathematical, statistical, and biological perspectives. The two articles in the mathematics category discuss optimal control strategies to limit the spread of COVID-19 in Italy and Jakarta, Indonesia, using quarantine, testing, and medical treatment. The statistics category features 4 articles that investigate the impact of temperature on the spread of COVID-19 in Gulf countries, the development of novel hybrid models for predicting COVID-19 in Kuwait, forecasting using basic reproduction number dynamics to analyze the pandemic's data, and a comparison of the multi-state models to assess the effect of antiviral treatment on SARS-CoV-2 infectious disease progression. The final 2 articles in the biology category focus on the bioinformatic analysis of antiviral medicinal compounds against SARS-CoV-2 proteases and the filtration efficiency of face masks and veils as protective measures during the COVID-19 pandemic.

Development of 2-chloroquinoline based heterocyclic frameworks as dual inhibitors of SARS-CoV-2 MPro and PLPro.

Evolution of new variants of SARS-CoV-2 warrant the need for the continued efforts in identifying target-oriented new drugs. Dual targeting agents against MPro and PLPro not only overcome the incomplete efficacy but also the drug resistance, which is common problem. Since both these are cysteine proteases, we designed 2-chloroquinoline based molecules with additional imine moiety in the middle as possible nucleophilic warheads. In the first round of design and synthesis, three molecules (C3, C4 and C5) inhibited (Ki < 2 µM) only MPro by binding covalently to C145 and one molecule (C10) inhibited both the proteases non-covalently (Ki < 2 µM) with negligible cytotoxicity. Further conversion of the imine in C10 to azetidinone (C11) improved the potency against both the enzymes in the nanomolar range (820 nM against MPro and 350 nM against PLPro) with no cytotoxicity. Conversion of imine to thiazolidinone (C12), reduced the inhibition by 3-5 folds against both the enzymes. Biochemical and computational studies suggest that C10-C12 bind in the substrate binding pocket of MPro and in the BL2 loop of the PLPro. Since these dual inhibitors have least cytotoxicity, they could be further explored as therapeutics against the SARS-CoV-2 and other analogous viruses.

Drug Design Strategies for the Treatment of Coronavirus Infection

The increasing size and density of the human population is leading to an increasing risk of infectious diseases that threaten to spread yet another pandemics. The widespread use of vaccination has reduced morbidity and mortality associated with viral infections and in some cases eradicated the virus from the population entirely. Regrettably, some virus species retain the ability to mutate rapidly and thus evade the vaccine-induced immune response. New antiviral drugs are therefore needed for the treatment and prevention of viral diseases. Modern research into the structures and properties of viral proteases, which are of key importance in the life cycle of viruses, makes it possible, in our opinion, to turn these enzymes into promising targets for the development of effective viral disease control methods.

In silico prediction of the inhibitory effect of phytochemical components extracted from Knautia sarajevensis on the main protease of SARS-CoV-2 virus

Essential role in replication and transcription of coronavirus makes the main protease of SARS-CoV-2 a great traget for drug design. The aim of this study was to predict structural interactions of compounds isolated from the Bosnian-Herzegovinian endemic plant Knautia sarajevensis (G. Beck) Szabo against the 3CLpro of SARS-CoV-2 virus. The three-dimensional crystal structure of SARS-CoV-2 main protease was retrieved from the RCSB Protein Data Bank and the three-dimensional structures of isolated compounds were obtained from the PubChem database. Active site was predicted using PrankWeb, while the preparation of protease and compounds was performed using AutoDock Tools and OpenBabel. Molecular docking was carried out using AutoDock Vina. Structural interactions are visualised and analyzed using PyMOL, LigPlus and UCSF Chimera. Apigenin, kaempferol, myricetin and quercetin showed the highest binding affinity for SARS-CoV-2 main protease and formed significant hydrogen bonds with the given protein. Results obtained in this study are in accordance with previous studies and showed that these compounds could potentially have antiviral effects against SARS-CoV-2. These findings indicate that K. sarajevensis could be potentially utilized as an adjuvant in the treatment of coronavirus disease 2019, but further pharmacological studies are required in order to prove the potential medicinal use of the plant.

Identification of Potent Natural Inhibitor Against Papain-Like Protease of SARS-CoV-2 an in Silico Approach

One of the most complicated tasks the healthcare system has faced in recent years has been the development of a curative treatment to stop the progression of the SARS CoV-2 virus. No consensus has been reached on a medical cure to slow the virus spread. From this point of view, investigating existing drugs such as SARS-CoV-2 inhibitors is an appropriate technique. With critical involvement in viral replication and host-immune suppression, Papain-like protease (PL-pro) is recognized as a key enzyme target for drug development among other SARS-CoV-2 druggable targets. Phytolignans have a wide range of physiological effects, making them an appealing drug for antiviral study. We used an insilico method to target SARS CoV-2 PL-pro with phytolignans in our investigation. The chemical structures of phytolignans were obtained from PubChem, whereas the protease structure 6WX4 was obtained from the Protein Data Bank website. The PyRx software was used for molecular docking.Of all the phytolignans examined, Sesamolin has the greatest binding affinity of-8.4 kcal/mol towards PL-pro.The docking results revealed that phytolignans are potent inhibitors of the SARS-CoV-2 papain-like protease and that they may be verified further in vitro and in vivo. Our findings suggest that Sesamolin might be used as a medication to block the action of SARS CoV-2 PL-pro. © 2023, DESIDOC.

Switch-on Fluorescence Analysis of Protease Activity with the Assistance of a Nickel Ion-Nitrilotriacetic Acid-Conjugated Magnetic Nanoparticle.

Heterogeneous protease biosensors show high sensitivity and selectivity but usually require the immobilization of peptide substrates on a solid interface. Such methods exhibit the disadvantages of complex immobilization steps and low enzymatic efficiency induced by steric hindrance. In this work, we proposed an immobilization-free strategy for protease detection with high simplicity, sensitivity and selectivity. Specifically, a single-labeled peptide with oligohistidine-tag (His-tag) was designed as the protease substrate, which can be captured by a nickel ion-nitrilotriacetic acid (Ni-NTA)-conjugated magnetic nanoparticle (MNP) through the coordination interaction between His-tag and Ni-NTA. When the peptide was digested by protease in a homogeneous solution, the signal-labeled segment was released from the substrate. The unreacted peptide substrates could be removed by Ni-NTA-MNP, and the released segments remained in solution to emit strong fluorescence. The method was used to determine protease of caspase-3 with a low detection limit (4 pg/mL). By changing the peptide sequence and signal reporters, the proposal could be used to develop novel homogeneous biosensors for the detection of other proteases.

Investigation of the potential inhibitor effects of lycorine on SARS-CoV-2 main protease (Mpro) using molecular dynamics simulations and MMPBSA

The main protease (Mpro or 3CLpro) plays important roles in viral replication and is one of attractive targets for drug development for SARS-CoV-2. In this study, we investigated the potential inhibitory effect of lycorine molecule as a ligand on SARS-CoV-2 using computational approaches. For this purpose, we conducted molecular docking and molecular dynamics simulations MM-PB(GB)SA analyses. The findings showed that the lycorine ligand was successfully docked with catalytic dyad (Cys145 and His41) of SARS-CoV-2 Mpro with binding affinity changing between -6.71 and -7.03 kcal mol-1. MMPB(GB)SA calculations resulted according to GB (Generalized Born) approach in a Gibbs free energy changing between -24.925-+01152 kcal/mol between lycorine and SARS-CoV-2 which is promising. PB (Poisson Boltzmann) approach gave less favorable energy (-2.610..0.2611 kcal mol-1). Thus, Entropy calculations from the normal mode analysis (S) were performed and it supported GB approach and conducted -23.100..6.4635 kcal mol-1. These results showed lycorine has a druggable potential but the drug effect of lycorine on COVID-19 is limited and experimental studies should be done with pharmacokinetic modifications that increase the drug effect of lycorine.

Lipid Lowering Natural Products Targeting hPCSK9 May Prevent the Severity of COVID-19 Infection

Background: The deadly outbreak of COVID-19 disease caused by novel SARS CoV2 has created an unprecedented global health crisis affecting every sectors of human life and enor-mous damage to world's economy. With >16.1 million infections and >650,000 deaths worldwide as of July 27, 2020, there is no treatment for this disease neither is there any available vaccine. Seri-ous research efforts are ongoing on all fronts including treatment, prevention and diagnosis to combat the spread of this infection. A number of targets that include both viral and host proteins have been identified and became part of intense investigation. In this respect the viral surface spike (S) glycoprotein caught the attention most. It is cleaved by multiple host proteases to allow recognition by host receptor human Angiotensin Converting Enzyme2 (hACE2) leading to fusion and viral re-plication. Natural products, small compounds, antioxidants, peptides, proteins, oligonucleotides, antibodies and other compounds are under investigation for development of antiviral agents against COVID-19. Objective(s): Recently cholesterol lowering phytocompounds Quercetin, Swertiamarin and Berberine which promote human Low Density Lipoprotein Receptor (hLDLR) via inhibition of human Pro-protein Convertase Subtilisin Kexin9 (hPCSK9) have been shown to block viral infections caused by ebola, influenza, Respiratory Syncytial Virus (RSV), Hepatitis C virus (HCV) and other RNA type viruses. Since SARS CoV2 is a RNA virus with similar genetic structure and infection machin-ery, it is hypothesised that these phytocompounds may also exhibit antiviral property against COVID-19. Method(s): Our above concept is based on recently published studies as well as our herein presented in silico modeling and computational data which suggested strong interactions of hPCSK9 with above phytocompounds and most importantly with hACE2 following its complexation with receptor binding domain (RBD) of SARS CoV2 S protein. Result(s): These results and a proposed schematic model showing association of hPCSK9 with SARS CoV2 infection are presented in this manuscript. It is proposed that hPCSK9 plays the role of a co-receptor in binding with hACE2:RBD complex and thereby facilitates viral fusion. Conclusion(s): Our studies suggest that PCSK9 inhibitors may provide beneficial effect against COVID-19 infection by retarding viral fusion through displacement of bound hPCSK9 from its complex with ACE2:RBD of SARS CoV2 S protein.Copyright © 2021 Bentham Science Publishers.

Study in-silico oleanane triterpenoids in Aquilaria spp. as a COVID-19 antiviral

Covid-19, a disease characterized by Severe Acute Respiratory Syndrome, is caused by Coronavirus-2 (SARS-CoV-2). This virus causes tissue damage and a decrease in the respiratory system. Agarwood (Aquilaria spp) is a plant that has various pharmacological activities, including relieving respiratory diseases. One of the several secondary metabolites reported in Aquilaria spp. is oleanane triterpenoids, suspected of having antiviral activity. This research was aimed to determine the potential of oleanane triterpenoids from Agarwood as a covid-19 antiviral by in silico study. The research methods were molecular docking, prediction of Lipinski rules of five, and prediction of ADME. As a receptor, main protease (Mpro) Covid-19 was used. The four oleanane triterpenoid compounds in Agarwood demonstrated a higher affinity for the main protease covid-19 (G 11-oxo-beta-amyrin = -9.8 kcal/mol, G hederagenin-an = -9.6 kcal/mol, G 3beta-acetoxyfriedelane = -9.4 kcal/mol, G ursolic acid = -9.5 kcal/mol) than Lopinavir (G = -6.2 kcal/mol) and Remdesivir (G = -7.2 kcal/mol). The major amino acids involved in ligand and receptor interactions are methionine 49 and 165, proline 168, glutamine 189, arginine 188, and threonine 25. According to the prediction of Lipinski's rule of five and ADME, hederageninan is potential for development as oral medicine.

SARS-CoV-2 morphology, genome, life cycle and our bodies' immune response: a review Ilyes Zatla, Lamia Boublenza, Hafida Hassaine

A novel coronavirus strain has been testing the capabilities of our modern world and suffocating health care systems, while bringing together scientist's researches and governmental powers, to fight off its robust viral disease. A new zoonotic pathogenic member of the human coronaviruses, that was first documented in Wuhan, China, has crossed the species barrier to infect humans and caused an outbreak of viral pneumonia. In this brief review, we'll discuss the virology of SARS-CoV-2, the virus that causes COVID-19, covering the general structure of the virus, its genetics and its process of replication. SARS-CoV-2 gets into the cell through the recognition of the angiotensin-converting enzyme 2 (ACE2) receptors by the spike glycoprotein, with the aid of the priming protein transmembrane serine protease 2 (TMPRSS2), which is important for its activation, and replicates as a result of a complex process that involves RNA synthesis, proofreading and capping.

Efficacy evaluation of quercetin and its analogues on the main protease enzyme of the COVID-19 using molecular docking studies

Introduction: COVID-19 is an acute respiratory infectious disease caused by the SARS-CoV-2 virus. There is an urgent need to discover antiviral drugs for better performance against new strains of coronaviruses (CoVs) due to the rapid spread of the disease despite scientific advances in vaccine development. This study aimed to evaluate the efficacy of quercetin and its analogues on the COVID-19 Mpro enzyme. Material & Methods: In this descriptive-analytical study, the three-dimensional structures of quercetin analogues (20 compounds), standard drugs (ritonavir and lopinavir), and the COVID-19 Mpro enzyme were obtained from PubChem and PDB databases for bioinformatics study, respectively. Molecular docking studies of the compounds on theMpro were performed using MOE-2014 software. Afterward, the physicochemical properties and biological activity of the compounds were predicted using Swiss ADME, PASS, and Swiss Target Prediction software. Findings: The findings of the present study showed that the most important bonds involved in drug-receptor binding are hydrogen, hydrophobic, and - interaction bonds. The best docking results were obtained for Baicalein, Genistein, Naringenin, and Quercetin compounds with strong binding energy (-12.83 to -13.54 kcal/mol), compared to ritonavir and lopinavir. These compounds have a greater tendency to bind to the catalytic amino acids His41 and Cys145 and other key amino acids of the active site of the COVID-19 Mpro enzyme. Discussion & Conclusion: Based on the results of bioinformatics studies, quercetin analogues had more effective inhibition than standard chemical drugs due to their suitable placement in the active site of the main protease enzyme of COVID-19 and can be good candidates for in vitro and in vivo studies.

SARS-CoV-2 Spike-Mediated Entry and Its Regulation by Host Innate Immunity.

The constantly evolving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) fuel the worldwide coronavirus disease (COVID-19) pandemic. The spike protein is essential for the SARS-CoV-2 viral entry and thus has been extensively targeted by therapeutic antibodies. However, mutations along the spike in SARS-CoV-2 VOC and Omicron subvariants have caused more rapid spread and strong antigenic drifts, rendering most of the current antibodies ineffective. Hence, understanding and targeting the molecular mechanism of spike activation is of great interest in curbing the spread and development of new therapeutic approaches. In this review, we summarize the conserved features of spike-mediated viral entry in various SARS-CoV-2 VOC and highlight the converging proteolytic processes involved in priming and activating the spike. We also summarize the roles of innate immune factors in preventing spike-driven membrane fusion and provide outlines for the identification of novel therapeutics against coronavirus infections.

In silico analysis of the antidepressant fluoxetine and related drugs at SARS-CoV-2 main protease (Mpro) and papain-like protease (PLpro).

BACKGROUND: SARS-CoV-2 main protease (Mpro or 3CLpro) and papain-like protease (PLpro) are common viral targets for repurposed drugs to combat COVID-19 disease. Recently, several anti-depressants (such as fluoxetine, venlafaxine and citalopram) belonging to the Selective Serotonin Reuptake Inhibitors (SSRIs) and the Serotonin-Norepinephrine Reuptake Inhibitors (SNRI) classes have been shown to in vitro inhibit viral replication. AIM: Investigate a possible action of fluoxetine and derivatives on SARS-CoV-2 protease sites. METHODS: molecular docking was performed using AutoDock Vina. Both proteases structures and different drugs conformations were used to explore the possibility of SARS-CoV-2 inhibition on a Mpro or PLpro related pathway. Drug structures were obtained by optimization with the Avogadro software and MOPAC using PM6 method. Results were analysed on Discovery Studio Visualizer. RESULTS: The results indicated that Mpro interacted in a thermodynamically favorable way with fluoxetine, venlafaxine, citalopram, atomoxetine, nisoxetine and norfluoxetine in the region of the active site, whether PLpro conformers did not come close to active site. CONCLUSION: In an in silico perspective, it is likely that the SSRIs and other anti-depressants could interact with Mpro and cause the enzyme to malfunction. Unfortunately, the same drugs did not present similar results on PLpro crystal, therefore no inhibition is expected on an in vitro trial. Anyway, in vitro test are necessary for the better understanding the links between SARS-CoV-2 proteases and anti-depressants.