scholarly journals Molecular Docking Studies on the Anti-viral Effects of Compounds From Kabasura Kudineer on SARS-CoV-2 3CLpro

2020 ◽  
Vol 7 ◽  
Author(s):  
Savariar Vincent ◽  
Selvaraj Arokiyaraj ◽  
Muthupandian Saravanan ◽  
Manoj Dhanraj
Keyword(s):  
Molecular Docking ◽  
Critical Role ◽  
Drug Repurposing ◽  
Docking Studies ◽  
World Health ◽  
Synthetic Drugs ◽  
Energy Score ◽  
Main Protease ◽  
Novel Coronavirus ◽  
Health Organization

The COVID-19 has now been declared a global pandemic by the World Health Organization. No approved drug is currently available; therefore, an urgent need has been developed for any antiviral therapy for COVID-19. Main protease 3CLpro of this novel Coronavirus (SARS-CoV-2) play a critical role in the disease propagation, and hence represent a crucial target for the drug discovery. Herein, we have applied a bioinformatics approach for drug repurposing to identify the possible potent inhibitors of SARS-CoV-2 main proteases 3CLpro (6LU7). In search of the anti-COVID-19 compound, we selected 145 phyto-compounds from Kabasura kudineer (KK), a poly-herbal formulation recommended by AYUSH for COVID-19 which are effective against fever, cough, sore throat, shortness of breath (similar to SARS-CoV2-like symptoms). The present study aims to identify molecules from natural products which may inhibit COVID-19 by acting on the main protease (3CLpro). Obtained results by molecular docking showed that Acetoside (−153.06), Luteolin 7 -rutinoside (−134.6) rutin (−133.06), Chebulagic acid (−124.3), Syrigaresinol (−120.03), Acanthoside (−122.21), Violanthin (−114.9), Andrographidine C (−101.8), myricetin (−99.96), Gingerenone -A (−93.9), Tinosporinone (−83.42), Geraniol (−62.87), Nootkatone (−62.4), Asarianin (−79.94), and Gamma sitosterol (−81.94) are main compounds from KK plants which may inhibit COVID-19 giving the better energy score compared to synthetic drugs. Based on the binding energy score, we suggest that these compounds can be tested against Coronavirus and used to develop effective antiviral drugs.

scholarly journals Naturally Occurring Anthraquinones as Potential Inhibitors of SARS-CoV-2 Main Protease: A Molecular Docking Study

2020 ◽  
Author(s):  
Sourav Das ◽  
Atanu Singha Roy
Keyword(s):  
Molecular Docking ◽  
Drug Targets ◽  
Docking Study ◽  
Docking Studies ◽  
World Health ◽  
Molecular Docking Study ◽  
Inhibitory Potential ◽  
Novel Coronavirus ◽  
Health Organization ◽  
Potential Inhibitors

<i>Background:</i> The novel coronavirus (COVID-19) has quickly spread throughout the globe, affecting millions of people. The World Health Organization (WHO) has recently declared this infectious disease as a pandemic. At present, several clinical trials are going on to identify possible drugs for treating this infection. SARS-CoV-2 M<sup>pro</sup> is one of the most critical drug targets for the blockage of viral replication. <i>Method:</i> The blind molecular docking analyses of natural anthraquinones with SARS-CoV-2 M<sup>pro</sup> were carried out in an online server, SWISSDOCK, which is based on EADock DSS docking software. <i>Results: </i>Blind molecular docking studies indicated that several<i> </i>natural antiviral anthraquinones could prove to be effective inhibitors for SARS-CoV-2 M<sup>pro</sup> of COVID-19 as they bind near the active site having the catalytic dyad, HIS41 and CYS145 through non-covalent forces. The anthraquinones showed less inhibitory potential as compared to the FDA approved drug, remdesivir.<i></i> <p><b><i>Conclusion:</i></b><i> </i>Among the natural anthraquinones<i>, </i>alterporriol Q could be the most potential inhibitor of SARS-CoV-2 M<sup>pro</sup> among the natural anthraquinones studied here, as its ∆<i>G</i> value differed from that of remdesivir only by 0.51 kcal/ mol. The uses of these alternate compounds might be favorable for the treatment of the COVID-19.</p>

scholarly journals Hispidin and Lepidine E: two Natural Compounds and Folic acid as Potential Inhibitors of 2019-novel coronavirus Main Protease (2019-nCoVMpro), molecular docking and SAR study

2020 ◽  
Vol 16 ◽  
Author(s):  
Talia Serseg ◽  
Khedidja Benarous ◽  
Mohamed Yousfi
Keyword(s):  
Molecular Docking ◽  
Folic Acid ◽  
Docking Study ◽  
Natural Compounds ◽  
Inhibitory Effect ◽  
World Health ◽  
Molecular Docking Study ◽  
Main Protease ◽  
Novel Coronavirus ◽  
Health Organization

: 2019-nCoVis a novel coronavirus was isolated and identified in 2019 in Wuhan, China. On 17 February and according to the world health organization, a number of 71 429 confirmed cases worldwide, among them 2162 new cases recorded in the last 24 hours. One month later the confirmed cases jumped to 179111, with 11525new cases in the last 24 hours, with 7426total deaths. There is no drug or vaccine for humanand animal coronavirus.The inhibition of 3CL hydrolase enzyme provides a promising therapeutic principle for developing treatments against CoViD-19.The 3CLpro (Mpro) known for involving in counteracting the host innate immune response.Thiswork presents the inhibitory effect of some natural compounds against 3CL hydrolase enzyme, and explain the main interactions in inhibitor-enzyme complex. Molecular docking study carried out using Autodock Vina. By screening several molecules, we identified three candidate agents that inhibit the main protease of coronavirus. Hispidin, lepidine E,and folic acid bound tightly in the enzyme, strong hydrogen bonds have been formed (1.69-1.80Å) with the active site residues.This study provides a possible therapeutic strategy for CoViD-19.

scholarly journals Naturally Occurring Anthraquinones as Potential Inhibitors of SARS-CoV-2 Main Protease: A Molecular Docking Study

2020 ◽  
Author(s):  
Sourav Das ◽  
Atanu Singha Roy
Keyword(s):  
Molecular Docking ◽  
Drug Targets ◽  
Docking Study ◽  
Docking Studies ◽  
World Health ◽  
Molecular Docking Study ◽  
Inhibitory Potential ◽  
Novel Coronavirus ◽  
Health Organization ◽  
Potential Inhibitors

<i>Background:</i> The novel coronavirus (COVID-19) has quickly spread throughout the globe, affecting millions of people. The World Health Organization (WHO) has recently declared this infectious disease as a pandemic. At present, several clinical trials are going on to identify possible drugs for treating this infection. SARS-CoV-2 M<sup>pro</sup> is one of the most critical drug targets for the blockage of viral replication. <i>Method:</i> The blind molecular docking analyses of natural anthraquinones with SARS-CoV-2 M<sup>pro</sup> were carried out in an online server, SWISSDOCK, which is based on EADock DSS docking software. <i>Results: </i>Blind molecular docking studies indicated that several<i> </i>natural antiviral anthraquinones could prove to be effective inhibitors for SARS-CoV-2 M<sup>pro</sup> of COVID-19 as they bind near the active site having the catalytic dyad, HIS41 and CYS145 through non-covalent forces. The anthraquinones showed less inhibitory potential as compared to the FDA approved drug, remdesivir.<i></i> <p><b><i>Conclusion:</i></b><i> </i>Among the natural anthraquinones<i>, </i>alterporriol Q could be the most potential inhibitor of SARS-CoV-2 M<sup>pro</sup> among the natural anthraquinones studied here, as its ∆<i>G</i> value differed from that of remdesivir only by 0.51 kcal/ mol. The uses of these alternate compounds might be favorable for the treatment of the COVID-19.</p>

scholarly journals An evidence-based systematic review on emerging therapeutic and preventive strategies to treat novel coronavirus (SARS-CoV-2) during an outbreak scenario

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Anupama M. Gudadappanavar ◽  
Jyoti Benni
Keyword(s):  
Antiviral Drug ◽  
Drug Repurposing ◽  
Respiratory Illness ◽  
World Health ◽  
Recombinant Vaccines ◽  
Subunit Vaccines ◽  
Coronavirus Infection ◽  
Novel Coronavirus ◽  
Health Organization ◽  
Full Length Genome

AbstractA novel coronavirus infection coronavirus disease 2019 (COVID-19) emerged from Wuhan, Hubei Province of China, in December 2019 caused by SARS-CoV-2 is believed to be originated from bats in the local wet markets. Later, animal to human and human-to-human transmission of the virus began and resulting in widespread respiratory illness worldwide to around more than 180 countries. The World Health Organization declared this disease as a pandemic in March 2020. There is no clinically approved antiviral drug or vaccine available to be used against COVID-19. Nevertheless, few broad-spectrum antiviral drugs have been studied against COVID-19 in clinical trials with clinical recovery. In the current review, we summarize the morphology and pathogenesis of COVID-19 infection. A strong rational groundwork was made keeping the focus on current development of therapeutic agents and vaccines for SARS-CoV-2. Among the proposed therapeutic regimen, hydroxychloroquine, chloroquine, remdisevir, azithromycin, toclizumab and cromostat mesylate have shown promising results, and limited benefit was seen with lopinavir–ritonavir treatment in hospitalized adult patients with severe COVID-19. Early development of SARS-CoV-2 vaccine started based on the full-length genome analysis of severe acute respiratory syndrome coronavirus. Several subunit vaccines, peptides, nucleic acids, plant-derived, recombinant vaccines are under pipeline. This article concludes and highlights ongoing advances in drug repurposing, therapeutics and vaccines to counter COVID-19, which collectively could enable efforts to halt the pandemic virus infection.

Phytoconstituents in the Management of Covid-19: Demystifying the Fact

Drug Research ◽  
2022 ◽  
Author(s):  
Md. Abul Barkat ◽  
Pawan Kaushik ◽  
Harshita Abul Barkat ◽  
Mohammad Idreesh Khan ◽  
Hazrina Ab Hadi
Keyword(s):  
Therapeutic Agent ◽  
Clinical Development ◽  
World Health ◽  
Therapeutic Drug ◽  
Scientific Communities ◽  
Synthetic Drugs ◽  
Naturally Occurring ◽  
Deadly Disease ◽  
Novel Coronavirus ◽  
Health Organization

AbstractThe 2019-nCoV (COVID-19; novel coronavirus disease-2019) outbreak is caused by the coronavirus, and its continued spread is responsible for increasing deaths, social and economic burden. COVID-19 created a chaotic situation worldwide and claimed the lives of over 5,027,183 and 248,467,363 confirmed cases have been reported so far as per the data published by WHO (World Health Organization) till 5th November 2021. Scientific communities all over the world are toiling to find a suitable therapeutic drug for this deadly disease. Although till date no promising drug has been discovered for this COVID-19. However, as per the WHO, over 102 COVID-19 vaccines are in clinical development and 185 in pre-clinical development. Naturally occurring phytoconstituents possess considerable chemical richness in the form of anti-viral and anti-parasitic potential and have been extensively exploited for the same globally. Still, phytomedicine-based therapies are considered as the best available treatment option to minimize and treat the symptoms of COVID-19 because of the least possible side effects compared to synthetic drugs recommended by the physicians/clinicians. In this review, the use of plant chemicals as a possible therapeutic agent for severe acute respiratory syndrome coronavirus 2 (SARS CoV2) is highlighted with their proposed mechanism of action, which will prove fruitful and effective in finding a cure for this deadly disease.

Screening of Kabasura Kudineer Chooranam against COVID-19 through Targeting of Main Protease and RNA-Dependent RNA Polymerase of SARS-CoV-2 by Molecular Docking Studies

2020 ◽  
Vol 5 (4) ◽  
pp. 319-331
Author(s):  
K. Gopalasatheeskumar ◽  
Karthikeyen Lakshmanan ◽  
Anguraj Moulishankar ◽  
Jerad Suresh ◽  
D. Kumuthaveni Babu ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Rna Polymerase ◽  
Docking Studies ◽  
The Novel ◽  
Rna Dependent Rna Polymerase ◽  
Molecular Docking Studies ◽  
Main Protease ◽  
Short Span ◽  
Novel Coronavirus

COVID-19 is the infectious pandemic disease caused by the novel coronavirus. The COVID-19 is spread globally in a short span of time. The Ministry of AYUSH, India which promotes Siddha and other Indian system of medicine recommends the use of formulation like Nilavembu Kudineer and Kaba Sura Kudineer Chooranam (KSKC). The present work seeks to provide the evidence for the action of 74 different constituents of the KSKC formulation acting on two critical targets. That is main protease and SARS-CoV-2 RNAdependent RNA polymerase target through molecular docking studies. The molecular docking was done by using AutoDock Tools 1.5.6 of the 74 compounds, about 50 compounds yielded docking results against COVID-19 main protease while 42 compounds yielded against SARSCoV- 2 RNA-dependent RNA polymerase. This research has concluded that the KSKC has the lead molecules that inhibits COVID-19’s target of main protease of COVID-19 and SARS-CoV-2 RNA-dependent RNA polymerase.

scholarly journals In Silico Identification and Docking-Based Drug Repurposing Against the Main Protease of SARS-CoV-2, Causative Agent of COVID-19

2020 ◽  
Author(s):  
Yogesh Kumar ◽  
Harvijay Singh
Keyword(s):  
Virtual Screening ◽  
Active Site ◽  
Viral Infections ◽  
Drug Repurposing ◽  
Docking Study ◽  
Docking Studies ◽  
Main Protease ◽  
Novel Coronavirus ◽  
Approved Drugs

<div>The rapidly enlarging COVID-19 pandemic caused by novel SARS-coronavirus 2 is a global</div><div>public health emergency of unprecedented level. Therefore the need of a drug or vaccine that</div><div>counter SARS-CoV-2 is an utmost requirement at this time. Upon infection the ssRNA genome</div><div>of SARS-CoV-2 is translated into large polyprotein which further processed into different</div><div>nonstructural proteins to form viral replication complex by virtue of virus specific proteases:</div><div>main protease (3-CL protease) and papain protease. This indispensable function of main protease</div><div>in virus replication makes this enzyme a promising target for the development of inhibitors and</div><div>potential treatment therapy for novel coronavirus infection. The recently concluded α-ketoamide</div><div>ligand bound X-ray crystal structure of SARS-CoV-2 Mpro (PDB ID: 6Y2F) from Zhang et al.</div><div>has revealed the potential inhibitor binding mechanism and the determinants responsible for</div><div>involved molecular interactions. Here, we have carried out a virtual screening and molecular</div><div>docking study of FDA approved drugs primarily targeted for other viral infections, to investigate</div><div>their binding affinity in Mpro active site. Virtual screening has identified a number of antiviral</div><div>drugs, top ten of which on the basis of their bending energy score are further examined through </div><div>molecular docking with Mpro. Docking studies revealed that drug Lopinavir-Ritonavir, Tipranavir</div><div>and Raltegravir among others binds in the active site of the protease with similar or higher</div><div>affinity than the crystal bound inhibitor α-ketoamide. However, the in-vitro efficacies of the drug</div><div>molecules tested in this study, further needs to be corroborated by carrying out biochemical and</div><div>structural investigation. Moreover, this study advances the potential use of existing drugs to be</div><div>investigated and used to contain the rapidly expanding SARS-CoV-2 infection.</div>

Synthesis of New Thiosemicarbazones and Semicarbazones Containing the 1,2,3-1H-triazole-isatin Scaffold: Trypanocidal, Cytotoxicity, Electrochemical Assays, and Molecular Docking

2019 ◽  
Vol 15 (3) ◽  
pp. 240-256 ◽  
Author(s):  
Bianca N.M. Silva ◽  
Policarpo A. Sales Junior ◽  
Alvaro J. Romanha ◽  
Silvane M.F. Murta ◽  
Camilo H.S. Lima ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Docking Studies ◽  
World Health ◽  
Neglected Diseases ◽  
Alkyl Aryl ◽  
Development Of Resistance ◽  
Health Organization

Background: Chagas disease, also known as American trypanosomiasis, is classified as one of the 17 most important neglected diseases by the World Health Organization. The only drugs with proven efficacy against Chagas disease are benznidazole and nifurtimox, however both show adverse effects, poor clinical efficacy, and development of resistance. For these reasons, the search for new effective chemical entities is a challenge to research groups and the pharmaceutical industry. Objective: Synthesis and evaluation of antitrypanosomal activities of a series of thiosemicarbazones and semicarbazones containing 1,2,3-1H triazole isatin scaffold. Method: 5&'-(4-alkyl/aryl)-1H-1,2,3-triazole-isatins were prepared by Huisgen 1,3-dipolar cycloaddition and the thiosemicarbazones and semicarbazones were obtained by the 1:1 reactions of the carbonylated derivatives with thiosemicarbazide and semicarbazide hydrochloride, respectively, in methanol, using conventional reflux or microwave heating. The compounds were assayed for in vitro trypanocidal activity against Trypanosoma cruzi, the aetiological agent of Chagas disease. Beyond the thio/semicarbazone derivatives, isatin and triazole synthetic intermediates were also evaluated for comparison. Results: A series of compounds were prepared in good yields. Among the 37 compounds evaluated, 18 were found to be active, in particular thiosemicarbazones containing a non-polar saturated alkyl chain (IC50 = 24.1, 38.6, and 83.2 &µM; SI = 11.6, 11.8, and 14.0, respectively). To further elucidate the mechanism of action of these new compounds, the redox behaviour of some active and inactive derivatives was studied by cyclic voltammetry. Molecular docking studies were also performed in two validated protein targets of Trypanosoma cruzi, i.e., cruzipain (CRZ) and phosphodiesterase C (TcrPDEC). Conclusion: A class of thio/semicarbazones structurally simple and easily accessible was synthesized. Compounds containing thiosemicarbazone moieties showed the best results in the series, being more active than the corresponding semicarbazones. Our results indicated that the activity of these compounds does not originate from an oxidation-reduction pathway but probably from the interactions with trypanosomal enzymes.

scholarly journals Tackling the COVID-19 Pandemic- A Review

2021 ◽  
Vol 29 (2) ◽  
pp. 175-186
Author(s):  
CC Nganwuchu ◽  
K Habas ◽  
N Mohammed ◽  
M Osei Wusuansa ◽  
D Makanjuola ◽  
...  
Keyword(s):  
Drug Repurposing ◽  
Health Impact ◽  
Diagnostic Methods ◽  
World Health ◽  
Personal Hygiene ◽  
Diagnostic Tools ◽  
Wide Range ◽  
The World ◽  
Novel Coronavirus ◽  
Health Organization

Since December 2019, a new type of coronavirus called novel coronavirus (2019-nCoV, or COVID-19) was identified in Wuhan, China and on March 11, 2020, the World Health Organization (WHO) has declared the novel coronavirus (COVID-19) outbreak a global pandemic. With more than 101,797,158 confirmed cases, resulting in 3,451,354 deaths as of May 21, 2021, the world faces an unprecedented economic, social, and health impact. The clinical spectrum of COVID-19 has a wide range of manifestations, ranging from an asymptomatic state or mild respiratory symptoms to severe viral pneumonia and acute respiratory distress syndrome. Several diagnostic methods are currently available for detecting the coronavirus in clinical, research, and public health laboratories. Some tests detect the infection directly by detecting the viral RNA using real time reverse transcriptase polymerase chain reaction (RT-PCR) and other tests detect the infection indirectly by detecting the host antibodies. Additional techniques are using medical imaging diagnostic tools such as X-ray and computed tomography (CT). Various approaches have been employed in the development of COVID-19 therapies. Some of these approaches use drug repurposing (e.g. Remdesivir and Dexamethasone) and combinational therapy (e.g. Lopinavir/Ritonavir), whilst others aim to develop anti-viral vaccines (e.g. mRNA and antibody). Additionally, health experts integrate data sharing, provide with guidelines and advice to minimize the effects of the pandemic. These guidelines include wearing masks, avoiding direct contact with infectious people, respiratory and personal hygiene. Taken together, an extensive knowledge on transmission mechanisms, clinical spectrums, specific diagnostics methods, host-virus interactions are required to tackle this pandemic. J. Bio-Sci. 29(2): 175-186, 2021 (December)

scholarly journals In Silico Identification and Docking-Based Drug Repurposing Against the Main Protease of SARS-CoV-2, Causative Agent of COVID-19

2020 ◽  
Author(s):  
Yogesh Kumar ◽  
Harvijay Singh
Keyword(s):  
Virtual Screening ◽  
Active Site ◽  
Viral Infections ◽  
Drug Repurposing ◽  
Docking Study ◽  
Docking Studies ◽  
Main Protease ◽  
Novel Coronavirus ◽  
Approved Drugs

<div>The rapidly enlarging COVID-19 pandemic caused by novel SARS-coronavirus 2 is a global</div><div>public health emergency of unprecedented level. Therefore the need of a drug or vaccine that</div><div>counter SARS-CoV-2 is an utmost requirement at this time. Upon infection the ssRNA genome</div><div>of SARS-CoV-2 is translated into large polyprotein which further processed into different</div><div>nonstructural proteins to form viral replication complex by virtue of virus specific proteases:</div><div>main protease (3-CL protease) and papain protease. This indispensable function of main protease</div><div>in virus replication makes this enzyme a promising target for the development of inhibitors and</div><div>potential treatment therapy for novel coronavirus infection. The recently concluded α-ketoamide</div><div>ligand bound X-ray crystal structure of SARS-CoV-2 Mpro (PDB ID: 6Y2F) from Zhang et al.</div><div>has revealed the potential inhibitor binding mechanism and the determinants responsible for</div><div>involved molecular interactions. Here, we have carried out a virtual screening and molecular</div><div>docking study of FDA approved drugs primarily targeted for other viral infections, to investigate</div><div>their binding affinity in Mpro active site. Virtual screening has identified a number of antiviral</div><div>drugs, top ten of which on the basis of their bending energy score are further examined through </div><div>molecular docking with Mpro. Docking studies revealed that drug Lopinavir-Ritonavir, Tipranavir</div><div>and Raltegravir among others binds in the active site of the protease with similar or higher</div><div>affinity than the crystal bound inhibitor α-ketoamide. However, the in-vitro efficacies of the drug</div><div>molecules tested in this study, further needs to be corroborated by carrying out biochemical and</div><div>structural investigation. Moreover, this study advances the potential use of existing drugs to be</div><div>investigated and used to contain the rapidly expanding SARS-CoV-2 infection.</div>

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