COVID-19 Main Protease Research Articles

Structural dynamics of COVID-19 main protease

Based on the importance of protease enzymes in functioning some viruses particularly coronaviridae, we have carried out an in silico investigation on the biologically important, yet unmapped phenomenon of activity and internal dynamics of COVID-19 main protease (Mpro) via applying finite-temperature all-atom molecular dynamics simulations. Temperature quench echoes generated by applying two successive cooling signals have therefore been analyzed in terms of the temperature-temperature correlation function of the protease within the harmonic approximation. An exponentially decaying brand of behavior has been found for the calculated echo depth values with increasing time, which has accordingly led to a much small dephasing time of about 150 fs, revealing a significant anharmonicity and therefore an overall structural stiffness for the COVID-19 main protease.

Screening of plant-based natural compounds as a potential COVID-19 main protease inhibitor: an in silico docking and molecular dynamics simulation approach

A new strain of coronavirus (CoV) has been identified as SARS-CoV-2, which is responsible for the recent COVID-19 pandemic. Currently, there is no approved vaccine or drug available to combat the pandemic. COVID-19 main protease (Mpro) is a key CoV enzyme, which plays an important role in triggering viral replication and transcription, turns it into an attractive target. Therefore, we aim to screen natural products library to find out potential COVID-19 Mpro inhibitors. Plant-based natural compounds from Sigma-Aldrich plant profiler chemical library have been screened through virtual molecular docking and molecular dynamics simulation to identify potential inhibitors of COVID Mpro. Our virtual molecular docking results have shown that there are twenty-eight natural compounds with a greater binding affinity toward the COVID-19 Mpro inhibition site as compared to the co-crystal native ligand Inhibitor N3 (-7.9 kcal/mol). Also, molecular dynamics simulation results have confirmed that Peonidin 3-O-glucoside, Kaempferol 3-O-β–rutinoside, 4-(3,4-Dihydroxyphenyl)-7-methoxy-5-[(6-O-β-D-xylopyranosyl-β-D-glucopyranosyl)oxy]-2H-1-benzopyran-2-one, Quercetin-3-D-xyloside, and Quercetin 3-O-α-L-arabinopyranoside (selected based on the docking score) possess a significant amount of dynamic properties such as stability, flexibility and binding energy. Our In silco results suggests that all the above mention natural compounds have the potential to be developed as a COVID-19 Mpro inhibitor. But before that, it must go through under the proper preclinical and clinical trials for further scientific validation. Communicated by Ramaswamy H. Sarma

Pharmacoinformatics and hypothetical studies on allicin, curcumin, and gingerol as potential candidates against COVID-19-associated proteases

Medicinal plants have been known to provide the essential raw material for the majority of antiviral drugs. This study demonstrated the putative inhibitory potential of curcumin, allicin, and gingerol towards cathepsin K, COVID-19 main protease, and SARS-CoV 3 C-like protease. The pharmacokinetic properties were predicted through the SwissADME server while the corresponding binding affinity of the selected phytocompounds towards the proteins was computed using PyRx-Python Prescription 0.8 and the binding free energy were computed based on conventional molecular dynamics using LARMD server. The ADMET properties revealed all the drugs possess drug-like properties. Curcumin has the highest binding affinities with all the selected proteases while allicin has the lowest binding affinities towards the proteases. Moreover, it was observed that curcumin exhibited the highest binding free energy of −17.90 ± 0.23, −18.21 ± 0.25, and −9.67 ± 0.08 kcal/mol for Cathepsin K, COVID-19 main protease, and SARS-CoV 3 C-like protease, respectively. Based on the activities of the phytocompounds against coronavirus target proteases involved in the viral entry as evident from the results, the study, therefore, suggests that these phytocompounds could be valuable for the development of drugs useful for the prevention of coronavirus entry and replication. Communicated by Ramaswamy H. Sarma

Discovery of Some Antiviral Natural Products to Fight Against Novel Coronavirus (SARS-CoV-2) Using an In silico Approach.

Novel coronavirus is a type of enveloped viruses with a single-stranded RNA enclosing helical nucleocapsid. The envelope consists of spikes on the surface which are made up of proteins through which virus enters into human cells. Until now, there is no specific drug or vaccine available to treat COVID-19 infection. In this scenario, reposting of drug or active molecules may provide rapid solution to fight against this deadly disease. We selected 30 phytoconstituents from the different plants which are reported for antiviral activities against coronavirus (CoVs) and performed in silico screening to find out phytoconstituents which have potency to inhibit specific target of the novel coronavirus. We performed molecular docking studies on three different proteins of novel coronavirus, namely COVID-19 main protease (3CL pro), papain-like protease (PL pro) and spike protein (S) attached to ACE2 binding domain. The screening of the phytoconstituents on the basis of binding affinity compared to standard drugs. The validations of screened compounds were done using ADMET and bioactivity prediction. We screened five compounds biscoclaurine, norreticuline, amentoflavone, licoricidin and myricetin, using in silico approach. All compounds were found safe in In silico toxicity studies. Bioactivity prediction reveals that these compounds may act through protease or enzyme inhibition. Results of compound biscoclaurine norreticuline were more interesting as this biscoclaurine had higher binding affinity for the target 3CLpro and PLpro targets and norreticuline had a higher binding affinity for the target PLpro and Spike protein. Our study concludes that these compounds could be further explored rapidly as it may have potential to fight against COVID-19.

In silico binding studies with b-sitosterol and some of its fatty acid esters to 3C-like protease of SARS-CoV-2

COVID-19, a coronavirus (SARS-CoV-2) caused disease has turned into a pandemic with no therapeutics in the form of drugs or vaccines yet in sight. The objective of this study was to evaluate in molecular docking studies the binding energies of b-sitosterol (a phytosterol) and some of its fatty acid esters to the main protease of COVID-19, otherwise known as the 3C-like protease or 3CLpro, (PDB ID: 6LU7) in an attempt to discover possible lead compounds or drugs against the virus as a means to contain the pandemic. Molecular docking (blind) was done with the help of Autodock Vina. Seven fatty acid esters of b-sitosterol (a major phytosterol) were evaluated. While b-sitosterol gave a binding energy of -7.0 kcal/mol, b-sitosterol-acetate and b-sitosteryl-ferulate gave binding energies of -6.9 and -7.8 kcal/mol, respectively. The other esters gave lower binding energies. As a result, the ferulic acid ester of b-sitosterol has a greater probability of being a COVID-19 therapeutic.

Exploration of inhibitory action of Azo imidazole derivatives against COVID-19 main protease (Mpro): A computational study

Four novel ionic liquid tagged azo-azomethine derivatives (L1-L4) have been prepared by the condensation reaction of azo-coupled ortho-vaniline precursor with amino functionalised imidazole derivative and the synthesized derivatives (L1-L4) have been characterized by different analytical and spectroscopic techniques. Molecular docking studies were carried out to ascertain the inhibitory action of studied ligands (L1-L4) against the Main Protease (6LU7) of novel coronavisrus (COVID-19). The result of the docking of L1-L4 showed a significant inhibitory action against the Main protease (Mpro) of SARS-CoV-2 and the binding energy (ΔG) values of the ligands (L1-L4) against the protein 6LU7 have found to be −7.7 Kcal/mole (L1), −7.0 Kcal/mole (L2), −7.9 Kcal/mole (L3), and −7.9 Kcal/mole (L4).The efficiency of the ligands has been compared with the FDA approved and clinically trial drugs such as remdesivir, Chloroquin and Hydroxychloroquin and native ligand N3 of main protease 6LU7 to ascertain the inhibitory potential of the studied ligands (L1-L4) against the protein 6LU7. Pharmacokinetic properties (ADME) of the ligands (L1-L4) have also been studied.

Amoxicillin and Clavulanate as Potential Multiple Effect Inhibitors of 2019 Novel Coronavirus Main Protease and RNA-Dependent RNA Polymerase with Strong Receptor-Binding Domain (RBD), Molecular Docking and SAR Study

SARS-CoV-2 is a novel coronavirus was isolated and identified first time in 2019 in Wuhan, China. Nowadays, it is a worldwide danger and the WHO named it as a pandemic. With a number of 5,593,631 as confirmed cases, and 353,334 as deaths. On 17 February, we have started our researches for finding potential inhibitors for COVID-19 main protease, especially after publishing the first crystalline structure of this protein in the PDB with PDB ID: 6lu7. We have found three potent molecules Hispidin, Folic acid and Lepidine E with Ki values 5.21, 3.71 and 1.89 μM respectively. Continuing the same context and in order to determine more inhibitors as potential strategy for COVID-19 treatment by molecular docking. We detected Amoxicillin and clavulanate as very strong inhibitors with a rate of 100% to the nCov-19 main protease and RNA-dependent RNA polymerase by several hydrogen bonds and hydrophobic interactions. In addition, we have docked both inhibitors to Spike protein domain of the virus responsible for its binding to the ACE2 receptors in the lungs and other vital organs. The results show that the ligands bound tightly with this latter confirming multiple effect and target of the drugs. Funding Statement: DGRSDT of Algeria Declaration of Interests: None to declare Ethics Approval Statement: Not needed

Hydroxychloroquine and curcumin conjugates as multifunctional co drugs for the potential treatment of COVID-19: An in-silico based study

The present study has been undertaken to search the novel co drugs for fighting against the COVID-19 disease through an in- silico approach. We have designed eight co drugs by merging two drugs namely hydroxychloroquine, used in the treatment of COVID-19 and curcumin an immuno modulator. The two drugs were linked through a bio-cleavable hydrolyzable linker by three-step process. The designed co drugs were subjected for molecular docking studies to know their therapeutic efficacy against the COVID-19 main protease (Mpro) and Interleukin-1β. The designed co drugs have a promising binding affinity towards Mpro in the narrow range of binding energies between -28.2498 to -35.8648 kcal/mol when compared to the standard Remdesivir which has -21.8600 kcal/mol. Similarly the binding energies of designed co drugs against Interleukin -1β range between -25.8032 to -34.6973 kcal/mol when compared to the standard curcumin which has -17.3274 kcal/mol. Our findings demonstrated that the designed co drugs may be useful for the treatment of viral respiratory infection due to their additive therapeutic actions on the viral protein and modulating the immune response synergistically.

Virtual screening, molecular docking studies and DFT calculations of FDA approved compounds similar to the non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was confirmed as the causative virus of COVID-19 disease, which is currently a worldwide pandemic. Efavirenz, a non-nucleoside reverse transcriptase inhibitor (NNRTI), is one of the most potent chemical compounds proposed to treat COVID-19 infection. We, therefore, performed virtual screening on FDA approved drugs that are similar to the efavirenz moiety. Subsequently, the compounds were subjected to screening by analyzing their drug-likeness, such as Lipinski's rule of five and ADMET properties. Molecular docking study revealed that Met165, His41, His163, and Phe140 were important interacting residues for COVID-19 main protease receptor-ligand interaction. Five top-ranked compounds, podophyllotoxin, oxacillin, lovastatin, simvastatin, and gefitinib, were selected by virtual screening and docking studies. The highest occupied molecular (HOMO) orbital, lowest unoccupied molecular orbital (LUMO) and energy gap values was calculated using density functional theory (DFT). The results of the study showed that lovastatin and simvastatin might be considered as lead compounds for further development for COVID-19 main protease inhibitors.

In-Silico approach for identification of effective and stable inhibitors for COVID-19 main protease (Mpro) from flavonoid based phytochemical constituents of Calendula officinalis

The recent outbreak of the coronavirus disease COVID-19 is putting the world towards a great threat. A recent study revealed COVID-19 main protease (Mpro) is responsible for the proteolytic mutation of this virus and is essential for its life cycle. Thus inhibition of this protease will eventually lead to the destruction of this virus. In-Silico Molecular docking was performed with the Native ligand and the 15 flavonoid based phytochemicals of Calendula officinals to check their binding affinity towards the COVID-19 main protease. Finally, the top 3 compounds with the highest affinity have been chosen for molecular dynamics simulation to analyses their dynamic properties and conformational flexibility or stability. In-Silico Docking showed that major phytochemicals of Calendula officinals i.e. rutin, isorhamnetin-3-O-β-D, calendoflaside, narcissin, calendulaglycoside B, calenduloside, calendoflavoside have better binding energy than the native ligand (inhibitor N3). MD simulation of 100 ns revealed that all the protease-ligand docked complexes are overall stable as compare to Mpro-native ligand (inhibitor N3) complex. Overall, rutin and caledoflaside showed better stability, compactness, and flexibility. Our in silico (Virtual molecular docking and Molecular dynamics simulation) studies pointed out that flavonoid based phytochemicals of calendula (rutin, isorhamnetin-3-O-β-D, calendoflaside) may be highly effective for inhibiting Mpro which is the main protease for SARS-CoV-2 causing the deadly disease COVID-19. Rutin is already used as a drug and the other two compounds can be made available for future use. Thus the study points a way to combat COVID-19 by the use of major flavonoid based phytochemicals of Calendula officinals. Communicated by Ramaswamy H. Sarma

Screening of Siddha Herbal Formulation Maramanjal Kudineer Churnam Against COVID-19 Through Targeting of Main Protease and RNA-Dependent RNA Polymerase of SARS-CoV-2 by Molecular Docking Studies

Background: Corona virus disease (COVID-19) is an infectious pandemic disease caused by the newly discovered novel corona virus. It was first diagnosed in Wuhan, China. COVID-19 virus spreads by droplets of saliva or discharge from the nose of the infected person via coughs or sneezes. Recently on 07/07/2020 WHO acknowledged “Evidence emerging” of the airborne spread of the corona virus. According to WHO, globally as on 10/07/2020 05.30 GMT +5.30, there have been 1,20,15,193 confirmed cases of COVID-19 and 5,49,247 deaths reported. Currently, there is no specific treatment approved for COVID-19, although treatment and vaccines are under study. In India, Department of AYUSH promotes the Indian system of Medicine to treat COVID-19 and recommends the use of anti-viral Siddha formulations Nilavembu Kudineer and Kabasura Kudineer. The present study aims to work on Siddha formulation Maramanjal Kudineer Churnam (MKC) a step towards treatment for the COVID-19 and to create a scientific evidence for the use of MKC. Methods: Seventy-four phytoconstituents of the MKC formulation was selected for the molecular docking studies to act on two critical targets main protease and SARS-CoV-2 RNA-dependent RNA polymerase. The molecular docking study was performed by using MGL Tools 1.5.6. Results: Docking studies on the data set of 74 phytoconstituents present in MKC, 74 phytoconstituents developed a docking results against the target COVID-19 main protease and 74 phytoconstituents developed a docking results against the target SARS-CoV-2 RNA-dependent RNA polymerase. Conclusion: This research has concluded that the MKC has the lead molecules that inhibits COVID-19’s target of Main Protease of COVID-19 and SARS Cov-2 RNA-dependent RNA polymerase.

Computational investigation of potential inhibitors of novel coronavirus 2019 through structure-based virtual screening, molecular dynamics and density functional theory studies

Despite the intensive research efforts towards antiviral drug against COVID-19, no potential drug or vaccines has not yet discovered. Initially, the binding site of COVID-19 main protease was predicted which located between regions 2 and 3. Structure-based virtual screening was performed through a hierarchal mode of elimination technique after generating a grid box. This led to the identification of five top hit molecules that were selected on the basis of docking score and visualization of non-bonding interactions. The docking results revealed that the hydrogen bonding and hydrophobic interactions are the major contributing factors in the stabilization of complexes. The docking scores were found between −7.524 and −6.711 kcal/mol indicating strong ligand-protein interactions. Amino acid residues Phe140, Leu141, Gly143, Asn142, Thr26, Glu166 and Thr190 (hydrogen bonding interactions) and Phe140, Cys145, Cys44, Met49, Leu167, Pro168, Met165, Val42, Leu27 and Ala191 (hydrophobic interactions) formed the binding pocket of COVID-19 main protease. From identified hits, ZINC13144609 and ZINC01581128 were selected for atomistic MD simulation and density functional theory calculations. MD simulation results confirm that the protein interacting with both hit molecules is stabilized in the chosen POPC lipid bilayer membrane. The presence of lowest unoccupied molecular orbital (LUMO) and highest occupied molecular orbital (HOMO) in the hydrophobic region of the hit molecules leads to favorable ligand-protein contacts. The calculated pharmacokinetic descriptors were found to be in their acceptable range and therefore confirming their drug-like properties. Hence, the present investigation can serve as the basis for designing and developing COVID-19 inhibitors. Communicated by Ramaswamy H. Sarma

Screening of Potent Inhibitors Against 2019 Novel Coronavirus (Covid-19) from Alliumsativum and Allium cepa: An In Silico Approach

The infection of the global COVID-19 pandemic and the absence of any possible treatment options warrants the use of all available resources to find effective drugs against this scourge. Various ongoing researches have been searching for the new drug candidate against COVID-19 infection. The research objective is based on the molecular docking study of inhibition of the main protease of COVID-19 by natural compounds found in Allium sativum and Allium cepa. Lipinski rule of five and Autodock 4.2 was used by using the Lamarckian Genetic Algorithm to perform Molecular docking to analyze the probability of docking. Further, ADME analysis was also performed by using SwissADME, which is freely available on the web. In the present study, we identified S-Allylcysteine sulfoxide (Alliin), S-Propyl cysteine, S-Allylcysteine, S-Ethylcysteine, S-Allylmercaptocysteine, S-Methylcysteine, S-propyl L-cysteine with binding energies (-5.24, -4.49, -4.99, -4.91, -4.79, -4.76, -5.0 kcal/mol) as potential inhibitor candidates for COVID-19. Out of 7 selected compounds, alliin showed the best binding efficacy with target protein 6LU7. In silico ADME analysis revealed that these compounds are expected to have a standard drug-like property as well. Our findings propose that natural compounds from garlic and onion can be used as potent inhibitors against the main protease of COVID-19, which could be helpful in combating the COVID-19 pandemic.

Virtual screening based on molecular docking of possible inhibitors of Covid-19 main protease

Coronavirus (COVID-19) is an enveloped RNA virus that is diversely found in humans and that has now been declared a global pandemic by the World Health Organization. Thus, there is an urgent need to develop effective therapies and vaccines against this disease. In this context, this study aimed to evaluate in silico the molecular interactions of drugs with therapeutic indications for treatment of COVID-19 (Azithromycin, Baricitinib and Hydroxychloroquine) and drugs with similar structures (Chloroquine, Quinacrine and Ruxolitinib) in docking models from the SARS-CoV-2 main protease (M-pro) protein. The results showed that all inhibitors bound to the same enzyme site, more specifically in domain III of the SARS-CoV-2 main protease. Therefore, this study allows proposing the use of baricitinib and quinacrine, in combination with azithromycin; however, these computer simulations are just an initial step for conceiving new projects for the development of antiviral molecules.

In silico identification of potential inhibitors from Cinnamon against main protease and spike glycoprotein of SARS CoV-2

Cinnamon has been utilized to remedy a lot of afflictions of humans. Literary works illustrate that it possesses numerous biological activities. Our research study is intended to recognize the phyto-derived antiviral substances from Cinnamon against COVID-19 main protease enzyme and to understand the in silico molecular basis of its activity. In the present study, 48 isolates compounds from Cinnamon retrieved from the PubMed database, are subjected to docking analysis. Docking study was performed using Autodock vina and PyRx software. Afterwards, admetSAR, as well as DruLiTo servers, were used to investigate drug-likeness prophecy. Our study shows that the nine phytochemicals of Cinnamon are very likely against the main protease enzyme of COVID-19. Further MD simulations could identify Tenufolin (TEN) and Pavetannin C1 (PAV) as hit compounds. Utilizing contemporary strategies, these phyto-compounds from a natural origin might establish a reliable medication or support lead identification. Identified hit compounds can be further taken for in vitro and in vivo studies to examine their effectiveness versus COVID-19.

Recognition of Natural Products as Potential Inhibitors of COVID-19 Main Protease (Mpro): In-Silico Evidences

SARS-CoV-2 (2019-nCoV) emerged in 2019 and proliferated rapidly across the globe. Scientists are attempting to investigate antivirals specific to COVID-19 treatment. The 2019-nCoV and SARS-CoV utilize the same receptor of the host which is COVID-19 of the main protease (Mpro).COVID-19 caused by SARS-CoV-2 is burdensome to overcome by presently acquired antiviral candidates. So the objective and purpose of this work was to investigate the plants with reported potential antiviral activity. With the aid of in silico techniques such as molecular docking and druggability studies, we have proposed several natural active compounds including glycyrrhizin, bicylogermecrene, tryptanthrine, β-sitosterol, indirubin, indican, indigo, hesperetin, crysophanic acid, rhein, berberine and β-caryophyllene which can be encountered as potential herbal candidate exhibiting anti-viral activity against SARS-CoV-2. Promising docking outcomes have been executed which evidenced the worthy of these selected herbal remedies for future drug development to combat coronavirus disease.Graphic

An in silico approach for identification of novel inhibitors as potential therapeutics targeting COVID-19 main protease

Respiratory disease caused by a novel coronavirus, COVID-19, has been labeled a pandemic by the World Health Organization. Very little is known about the infection mechanism for this virus. More importantly, there are no drugs or vaccines that can cure or prevent a person from getting COVID-19. In this study, the binding affinity of 2692 protease inhibitor compounds that are known in the protein data bank, are calculated against the main protease of the novel coronavirus with docking and molecular dynamics (MD). Both the docking and MD methods predict the macrocyclic tissue factor–factor VIIa (PubChem ID: 118098670) inhibitor to bind strongly with the main protease with a binding affinity of −10.6 and −10.0 kcal/mol, respectively. The TF-FVIIa inhibitors are known to prevent the coagulation of blood and have antiviral activity as shown in the case of SARS coronavirus. Two more inhibitors, phenyltriazolinones (PubChem ID: 104161460) and allosteric HCV NS5B polymerase thumb pocket 2 (PubChem ID: 163632044) have shown antiviral activity and also have high affinity towards the main protease of COVID-19. Furthermore, these inhibitors interact with the catalytic dyad in the active site of the COVID-19 main protease that is especially important in viral replication. The calculated theoretical dissociation constants of the proposed COVID-19 inhibitors are found to be very similar to the experimental dissociation constant values of similar protease-inhibitor systems. Communicated by Ramaswamy H. Sarma

Inhibitory activity of hydroxychloroquine on COVID-19 main protease: An insight from MD-simulation studies

The present work is an investigation to test hydroxychloroquine as an inhibitor for the COVID-19 main protease. Molecular docking studies revealed a high docking score and interaction energies and decent level of docking within the cavity in protease moiety. Molecular dynamics simulations also lead to the evaluation of conformational energies, average H-bonding distance, RMSD plots etc. Large RMSD fluctuations for the first 2 ns seem to provide the conformational and rotational changes associated with the drug molecule when it comes into the vicinity on the protease matrix. Snapshots of structural changes with respect to time vividly indicates that drug molecule has a profound impact on the binding sites as well as overall geometry of the protease moiety. On the whole, hydroxyxhloroquine confers good inhibitory response to COVID-19 main protease. We hope the present study should help workers in the field to develop potential vaccines and therapeutics against the novel coronavirus.

Fractional-Order Susceptible-Infected Model: Definition and Applications to the Study of COVID-19 Main Protease.

We propose a model for the transmission of perturbations across the amino acids of a protein represented as an interaction network. The dynamics consists of a Susceptible-Infected (SI) model based on the Caputo fractional-order derivative. We find an upper bound to the analytical solution of this model which represents the worse-case scenario on the propagation of perturbations across a protein residue network. This upper bound is expressed in terms of Mittag-Leffler functions of the adjacency matrix of the network of inter-amino acids interactions. We then apply this model to the analysis of the propagation of perturbations produced by inhibitors of the main protease of SARS CoV-2. We find that the perturbations produced by strong inhibitors of the protease are propagated far away from the binding site, confirming the long-range nature of intra-protein communication. On the contrary, the weakest inhibitors only transmit their perturbations across a close environment around the binding site. These findings may help to the design of drug candidates against this new coronavirus.

Favipiravir May Acts as COVID-19 Main Protease PDB ID 6LU7 Inhibitor: Docking Analysis

Coronavirus is a well-known threat to the human being in the form of COVID-19. Virus replication may be controlled by inhibition of protease enzyme. Hence, well known 13 antiviral drugs have been observed by docking analysis for understanding the binding pattern of drugs with COVID-19 main protease PDB ID: 6LU7 for any possibilities of protease inhibition. For docking analysis PyRx- Python Prescription 0.8 was used. This analysis reveals that the essential amino acids involved in binding of antiviral drugs to COVID-19 main protease PDB ID: 6LU7 are Glycine (Gly), Serine (Ser), Cysteine (Cys), Leucine (Leu), Asparagine (Asn), Glutamine (Gln), Glutamic acid (Glu) and Threonine (Thr). After docking analysis, it was observed that Favipiravir maybe act as COVID-19 main protease inhibitor despite being vRNA polymerase inhibitor and may further be used in the treatment of COVID-19 infection.