In silico screening of FDA approved drugs predicts the therapeutic potentials of Antibiotic drugs against the papain like protease of SARS-CoV-2

2021 ◽  
pp. 4035-4039
Author(s):  
Vipul Kumar ◽  
Sudhakar Kancharla ◽  
Manoj Kumar Jena
Keyword(s):  
In Silico ◽  
Computational Study ◽  
Docking Study ◽  
Wild Type ◽  
In Silico Screening ◽  
Antibiotic Drugs ◽  
Experimental Validations ◽  
Novel Coronavirus ◽  
Approved Drugs ◽  
Fda Approved Drugs

Since the outbreak of severe acute respiratory syndrome corona Virus -2 (SARS-CoV-2) has happened in December 2019 in Wuhan, China, the cases of novel coronavirus disease (COVID-19) is rapidly increasing worldwide. In the absence of specific drugs against COVID-19, the fast and reliable choice would be repurposing of existing drugs. Here, we have chosen one of the crucial enzymes of the SARS-CoV-2, Papain like protease (PLpro) and its mutant C111S for the structure-based in-silico screening of the FDA approved drugs. Firstly, the alignment of the wild type and mutant PLpro was done, and no significant change in the global structure was observed. Then based on the docking study, we have reported the best 3 compounds against a mutant and wild type PLpro. These lead compounds include amikacin and mafenide, which are well-known antibiotics. The binding affinity, as well as number of polar and non-polar interactions, indicates their potential against the PLpro. This computational study strongly suggests the experimental validations of the predicted compounds for a confident claim.

scholarly journals In silico screening of FDA approved drugs reveals ergotamine and dihydroergotamine as potential coronavirus main protease enzyme inhibitors

2020 ◽  
Vol 27 (10) ◽  
pp. 2674-2682
Author(s):  
Arun Bahadur Gurung ◽  
Mohammad Ajmal Ali ◽  
Joongku Lee ◽  
Mohammad Abul Farah ◽  
Khalid Mashay Al-Anazi
Keyword(s):  
In Silico ◽  
Enzyme Inhibitors ◽  
In Silico Screening ◽  
Protease Enzyme ◽  
Main Protease ◽  
Approved Drugs ◽  
Fda Approved Drugs

In silico identification of novel kinase inhibitors targeting wild-type and T315I mutant ABL1 from FDA-approved drugs

2014 ◽  
Vol 10 (6) ◽  
pp. 1524 ◽  
Author(s):  
Huai-long Xu ◽  
Zi-jie Wang ◽  
Xiao-meng Liang ◽  
Xin Li ◽  
Zheng Shi ◽  
...  
Keyword(s):  
In Silico ◽  
Kinase Inhibitors ◽  
Wild Type ◽  
In Silico Identification ◽  
Approved Drugs ◽  
Fda Approved Drugs

scholarly journals In silico screening of potent inhibitors against COVID-19 key targets from a library of FDA-approved drugs

2021 ◽  
Author(s):  
Mohammad A. Elmorsy ◽  
Ahmed M. El-Baz ◽  
Nashwa H. Mohamed ◽  
Rafa Almeer ◽  
Mohamed M. Abdel-Daim ◽  
...  
Keyword(s):  
In Silico ◽  
In Silico Screening ◽  
Approved Drugs ◽  
Fda Approved Drugs

In silico identification of new anti-SARS-CoV-2 agents from bioactive phytocompounds targeting the viral spike glycoprotein and human TLR4

2021 ◽  
Vol 18 ◽  
Author(s):  
Nabarun Chandra Das ◽  
Rajendra Kumar Labala ◽  
Ritwik Patra ◽  
Asamanja Chattoraj ◽  
Suprabhat Mukherjee
Keyword(s):  
In Silico ◽  
Md Simulation ◽  
Docking Study ◽  
Spike Glycoprotein ◽  
Molecular Docking Study ◽  
S Protein ◽  
Proinflammatory Responses ◽  
Experimental Validations ◽  
The Stability ◽  
Novel Coronavirus

Background: The recent outbreak of novel coronavirus disease (COVID-19) pandemic caused by SARS-CoV-2 has posed a tremendous threat to mankind. The unavailability of a specific drug or vaccine has been the major concern to date. Spike (S) glycoprotein of SARS-CoV-2 plays the most crucial role in the viral infection and immunopathogenesis, and hence this protein appears to be an efficacious target for drug discovery. Objective: Identifying potent bioactive phytocompound that can target viral spike (S) glycoprotein and human TLR4 to reduce immunopathological manifestations of COVID-19. Method: A series of thirty (30) bioactive phytocompounds, previously documented for antiviral activity, were theoretically screened for their binding efficacy against key proteins related to pathogenesis of SARSCoV-2 namely viral spike (S) glycoprotein and human TLR4. MD simulation was employed to verify the postulations of molecular docking study and further ADME analysis was performed to predict the most effective one. Results: Studies hypothesized that two new phytochemicals viz. cajaninstilbene acid (-8.83 kcal/mol) and papaverine (-5.81 kcal/mol) might be the potent inhibitors of spike glycoprotein with stout binding affinity and favourable ADME attributes. MD simulation further ratified the stability of the docked complexes between the phytochemicals and S protein through strong hydrogen bonding. Our in silico data also indicated that cajaninstilbene acid and papaverine might block human TLR4 which could be useful to mitigate SARS-CoV-2-induced lethal proinflammatory responses. Conclusion: Experimental data collectively predict cajaninstilbene acid as the potential blocker of S protein which may be used as anti-viral against COVID-19 in the future. However, further experimental validations alongside toxicological detailing are needed for claiming the candidature of these molecules as future anti-corona therapeutics.

scholarly journals FDA-Approved Drugs Efavirenz, Tipranavir, and Dasabuvir Inhibit Replication of Multiple Flaviviruses in Vero Cells

2020 ◽  
Vol 8 (4) ◽  
pp. 599
Author(s):  
Michal Stefanik ◽  
James J. Valdes ◽  
Fortunatus C. Ezebuo ◽  
Jan Haviernik ◽  
Ikemefuna C. Uzochukwu ◽  
...  
Keyword(s):  
Human Health ◽  
Zika Virus ◽  
In Silico ◽  
Vero Cells ◽  
In Silico Screening ◽  
Tick Borne Encephalitis ◽  
Vector Borne ◽  
Tick Borne Encephalitis Virus ◽  
Approved Drugs ◽  
Fda Approved Drugs

Vector-borne flaviviruses (VBFs) affect human health worldwide, but no approved drugs are available specifically to treat VBF-associated infections. Here, we performed in silico screening of a library of U.S. Food and Drug Administration-approved antiviral drugs for their interaction with Zika virus proteins. Twelve hit drugs were identified by the docking experiments and tested in cell-based antiviral assay systems. Efavirenz, tipranavir, and dasabuvir at micromolar concentrations were identified to inhibit all VBFs tested; i.e., two representatives of mosquito-borne flaviviruses (Zika and West Nile viruses) and one representative of flaviviruses transmitted by ticks (tick-borne encephalitis virus). The results warrant further research into these drugs, either individually or in combination, as possible pan-flavivirus inhibitors.

Design and in-silico screening of Peptide Nucleic Acid (PNA) inspired novel pronucleotide scaffolds targeting COVID-19

2020 ◽  
Vol 16 ◽  
Author(s):  
Bichismita Sahu ◽  
Santosh Kumar Behera ◽  
Rudradip Das ◽  
Tanay Dalvi ◽  
Arnab Chowdhury ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
In Silico ◽  
Peptide Nucleic Acid ◽  
Large Set ◽  
Nonstructural Proteins ◽  
In Silico Screening ◽  
Replication Process ◽  
Enveloped Virus ◽  
Treatment Regimens ◽  
Novel Coronavirus

Introduction: The outburst of the novel coronavirus COVID-19, at the end of December 2019 has turned itself into a pandemic taking a heavy toll on human lives. The causal agent being SARS-CoV-2, a member of the long-known Coronaviridae family, is a positive sense single-stranded enveloped virus and quite closely related to SARS-CoV. It has become the need of the hour to understand the pathophysiology of this disease, so that drugs, vaccines, treatment regimens and plausible therapeutic agents can be produced. Methods: In this regard, recent studies uncovered the fact that the viral genome of SARS-CoV-2 encodes nonstructural proteins like RNA dependent RNA polymerase (RdRp) which is an important tool for its transcription and replication process. A large number of nucleic acid based anti-viral drugs are being repurposed for treating COVID-19 targeting RdRp. Few of them are in the advanced stage of clinical trials including Remdesivir. While performing close investigation of the large set of nucleic acid based drugs, we were surprised to find that the synthetic nucleic acid backbone is explored very little or rare. Results: We have designed scaffolds derived from peptide nucleic acid (PNA) and subjected them for in-silico screening systematically. These designed molecules have demonstrated excellent binding towards RdRp. Compound 12 was found to possess similar binding affinity as Remdesivir with comparable pharmacokinetics. However, the in-silico toxicity prediction indicates compound 12 may be a superior molecule which can be explored further due to its excellent safety-profile with LD50 (12,000mg/kg) as opposed to Remdesivir (LD50 =1000mg/kg). Conclusion: Compound 12 falls in the safe category of class 6. Synthetic feasibility, equipotent binding and very low toxicity of this peptide nucleic acid derived compounds can serve as a leading scaffold to design, synthesize and evaluate many of similar compounds for the treatment of COVID-19.

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