Drug Repurposing Commonly Against Dengue Virus Capsid and SARS-CoV-2 Nucleocapsid: An in Silico Approach

10.26434/chemrxiv.12611861.v2 ◽

2020 ◽

Author(s):

Debica Mukherjee ◽

Rupesh Roy ◽

UPASANA RAY

Keyword(s):

Dengue Virus ◽

Capsid Protein ◽

In Silico ◽

Rna Binding ◽

Drug Repurposing ◽

Virus Capsid ◽

Approved Drugs ◽

Full Swing ◽

Fda Approved Drugs ◽

Virus Capsid Protein

In the middle of SARS-CoV-2 pandemic, dengue virus (DENV) is giving a silent warning as the season approaches nearer. There is no specific antiviral against DENV for use in the clinics. Thus, considering these facts we can potentially face both these viruses together increasing the clinical burden. The search for anti-viral drugs against SARS-CoV-2 is in full swing and repurposing of already ‘in-use’ drugs against other diseases or COVID-19 has drawn significant attention. Earlier we had reported few FDA approved anti-viral and anti-microbial drugs that could be tested for binding with SARS-CoV-2 nucleocapsid N terminal domain. We explored the possibility of interactions of the drugs screened for SARS-CoV2 with Dengue virus capsid protein. We report five FDA approved drugs that were seen to be docking onto the SARS-CoV-2 nucleocapsid RNA binding domain, also docking well with DENV capsid protein on the RNA binding site and/or the capsid’s membrane fusion domain. Thus, the present study proposes these five drugs as common antiviral candidates against both SARS-CoV-2 and DENV although the in silico study is subject to further validations.

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Drug Repurposing Commonly Against Dengue Virus Capsid and SARS-CoV-2 Nucleocapsid: An in Silico Approach

10.26434/chemrxiv.12611861 ◽

2020 ◽

Author(s):

Debica Mukherjee ◽

Rupesh Roy ◽

UPASANA RAY

Keyword(s):

Dengue Virus ◽

Capsid Protein ◽

In Silico ◽

Rna Binding ◽

Drug Repurposing ◽

Virus Capsid ◽

Approved Drugs ◽

Full Swing ◽

Fda Approved Drugs ◽

Virus Capsid Protein

In the middle of SARS-CoV-2 pandemic, dengue virus (DENV) is giving a silent warning as the season approaches nearer. There is no specific antiviral against DENV for use in the clinics. Thus, considering these facts we can potentially face both these viruses together increasing the clinical burden. The search for anti-viral drugs against SARS-CoV-2 is in full swing and repurposing of already ‘in-use’ drugs against other diseases or COVID-19 has drawn significant attention. Earlier we had reported few FDA approved anti-viral and anti-microbial drugs that could be tested for binding with SARS-CoV-2 nucleocapsid N terminal domain. We explored the possibility of interactions of the drugs screened for SARS-CoV2 with Dengue virus capsid protein. We report five FDA approved drugs that were seen to be docking onto the SARS-CoV-2 nucleocapsid RNA binding domain, also docking well with DENV capsid protein on the RNA binding site and/or the capsid’s membrane fusion domain. Thus, the present study proposes these five drugs as common antiviral candidates against both SARS-CoV-2 and DENV although the in silico study is subject to further validations.

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Computational Drug Repurposing Studies on SARS-CoV-2 Protein Targets

10.26434/chemrxiv.12315437.v1 ◽

2020 ◽

Author(s):

Guangfeng Zhou ◽

Lance Stewart ◽

Gabriella Reggiano ◽

Frank DiMaio

Keyword(s):

Experimental Validation ◽

Rna Binding ◽

Drug Repurposing ◽

Protein Targets ◽

Priority List ◽

Computational Docking ◽

Docking Protocol ◽

Approved Drugs ◽

Aids Drugs ◽

Fda Approved Drugs

To contribute to the combat of COVID-2019, we applied structure-based computational docking screens using flexible docking protocol of Rosetta GALigandDock against multiple potential SARS-CoV-2 protein targets, including the Nsp5 3-chymotrypsin-like protease (3CLpro), the Nsp3 ADP ribose phosphatase, the Nsp15 Endoribonuclease, the RNA binding domain of nucleocapsid phosphoprotein, the Nsp16 2'-O-MTase, Nsp14, and Nsp12 RNA-dependent RNA polymerase. Screening against a re-purposing library of 8,395 FDA approved drugs at various stages of drug development and various natural products from DrugBank, we found a total of 124 putative inhibitors with predicted binding ∆G less than -8.9 kcal/mol, including HIV-AIDS drugs Nelfinavir and Tipranavir, targeting 3Clpro with ∆G=-18.8 kcal/mol and ∆G=-16.6 kcal/mol respectively. These primarily involve binders to the Nsp5 3CLpro (37 hits) and the Nsp3 ADP ribose phosphatase (36 hits), with smaller numbers of hits to other targets. These small molecule putative inhibitors suggest a possible avenue for drug repurposing, and the identified compounds should serve as a high-priority list for experimental validation via co-crystallization, enzymatic and cell based assays.

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Computational Drug Repurposing Studies on SARS-CoV-2 Protein Targets

10.26434/chemrxiv.12315437 ◽

2020 ◽

Author(s):

Guangfeng Zhou ◽

Lance Stewart ◽

Gabriella Reggiano ◽

Frank DiMaio

Keyword(s):

Experimental Validation ◽

Rna Binding ◽

Drug Repurposing ◽

Protein Targets ◽

Priority List ◽

Computational Docking ◽

Docking Protocol ◽

Approved Drugs ◽

Aids Drugs ◽

Fda Approved Drugs

To contribute to the combat of COVID-2019, we applied structure-based computational docking screens using flexible docking protocol of Rosetta GALigandDock against multiple potential SARS-CoV-2 protein targets, including the Nsp5 3-chymotrypsin-like protease (3CLpro), the Nsp3 ADP ribose phosphatase, the Nsp15 Endoribonuclease, the RNA binding domain of nucleocapsid phosphoprotein, the Nsp16 2'-O-MTase, Nsp14, and Nsp12 RNA-dependent RNA polymerase. Screening against a re-purposing library of 8,395 FDA approved drugs at various stages of drug development and various natural products from DrugBank, we found a total of 124 putative inhibitors with predicted binding ∆G less than -8.9 kcal/mol, including HIV-AIDS drugs Nelfinavir and Tipranavir, targeting 3Clpro with ∆G=-18.8 kcal/mol and ∆G=-16.6 kcal/mol respectively. These primarily involve binders to the Nsp5 3CLpro (37 hits) and the Nsp3 ADP ribose phosphatase (36 hits), with smaller numbers of hits to other targets. These small molecule putative inhibitors suggest a possible avenue for drug repurposing, and the identified compounds should serve as a high-priority list for experimental validation via co-crystallization, enzymatic and cell based assays.

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Structural Basis of Antisickling Effects of Selected FDA Approved Drugs: A Drug Repurposing Study

Current Computer - Aided Drug Design ◽

10.2174/1573409914666180129163711 ◽

2018 ◽

Vol 14 (2) ◽

pp. 106-116 ◽

Cited By ~ 1

Author(s):

Olujide O. Olubiyi ◽

Maryam O. Olagunju ◽

James O. Oni ◽

Abidemi O. Olubiyi

Keyword(s):

Drug Repurposing ◽

Structural Basis ◽

Approved Drugs ◽

Fda Approved Drugs

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Screening of an FDA-Approved Library for Novel Drugs against Y. pestis

Antibiotics ◽

10.3390/antibiotics10010040 ◽

2021 ◽

Vol 10 (1) ◽

pp. 40

Author(s):

David Gur ◽

Theodor Chitlaru ◽

Emanuelle Mamroud ◽

Ayelet Zauberman

Keyword(s):

Drug Repurposing ◽

Mortality Rates ◽

Systematic Screening ◽

Antibiotic Resistant ◽

Gram Negative ◽

Therapy Initiation ◽

Novel Drugs ◽

Resistant Strains ◽

Approved Drugs ◽

Fda Approved Drugs

Yersinia pestis is a Gram-negative pathogen that causes plague, a devastating disease that kills millions worldwide. Although plague is efficiently treatable by recommended antibiotics, the time of antibiotic therapy initiation is critical, as high mortality rates have been observed if treatment is delayed for longer than 24 h after symptom onset. To overcome the emergence of antibiotic resistant strains, we attempted a systematic screening of Food and Drug Administration (FDA)-approved drugs to identify alternative compounds which may possess antibacterial activity against Y. pestis. Here, we describe a drug-repurposing approach, which led to the identification of two antibiotic-like activities of the anticancer drugs bleomycin sulfate and streptozocin that have the potential for designing novel antiplague therapy approaches. The inhibitory characteristics of these two drugs were further addressed as well as their efficiency in affecting the growth of Y. pestis strains resistant to doxycycline and ciprofloxacin, antibiotics recommended for plague treatment.

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