Virtual Screening Enabled Selection of Antiviral Agents Against Covid-19 Disease Targeting Coronavirus Endoribonuclease NendoU: Plausible Mechanistic Interventions in the Treatment of New Virus Strain

SARS-CoV-2 is the seventh coronavirus that is reported to cause infection in Homo sapiens. Considering its pandemic nature, development of newer and effective therapeutic strategies, drug repurposing in combination with target validation approaches has led to the identification of new antiviral molecules. In current work, we performed virtual screening and molecular docking of 8548 ligands on target protein coronavirus endoribonuclease NendoU (3VWW). The molecules selected includes FDA approved drugs along with investigational or experimental drugs recommended for anticancer, antiviral, antimicrobial, and antiprotozoal properties. The thorough selection and their rationality with Covid-19 led us to propose that FDA approved drug DB00876 (Eprosartan), Investigational drugs DB15063 (Inarigivir soproxil), DB12307 (Foretinib) and DB01813 an experimental drug may be repurposed for treatment of Covid-19 disease.

Virtual Screening Enabled Selection of Antiviral Agents Against Covid-19 Disease Targeting Coronavirus Endoribonuclease NendoU: Plausible Mechanistic Interventions in the Treatment of New Virus Strain

10.26434/chemrxiv.12198966 ◽

2020 ◽

Author(s):

Gaurav Joshi ◽

Ramarao Poduri

Keyword(s):

Virtual Screening ◽

Homo Sapiens ◽

Antiviral Agents ◽

Drug Repurposing ◽

Experimental Drugs ◽

Experimental Drug ◽

Investigational Drugs ◽

Approved Drugs ◽

Fda Approved Drugs ◽

SARS-CoV-2 is the seventh coronavirus that is reported to cause infection in Homo sapiens. Considering its pandemic nature, development of newer and effective therapeutic strategies, drug repurposing in combination with target validation approaches has led to the identification of new antiviral molecules. In current work, we performed virtual screening and molecular docking of 8548 ligands on target protein coronavirus endoribonuclease NendoU (6VWW). The molecules selected includes FDA approved drugs along with investigational or experimental drugs recommended for anticancer, antiviral, antimicrobial, and antiprotozoal properties. The thorough selection and their rationality with Covid-19 led us to propose that FDA approved drug DB00876 (Eprosartan), Investigational drugs DB15063 (Inarigivir soproxil), DB12307 (Foretinib) and DB01813 an experimental drug may be repurposed for treatment of Covid-19 disease.

Virtual Screening Enabled Selection of Antiviral Agents Against Covid-19 Disease Targeting Coronavirus Endoribonuclease NendoU: Plausible Mechanistic Interventions in the Treatment of New Virus Strain

10.26434/chemrxiv.12198966.v2 ◽

2020 ◽

Author(s):

Gaurav Joshi ◽

Ramarao Poduri

Keyword(s):

Virtual Screening ◽

Homo Sapiens ◽

Antiviral Agents ◽

Drug Repurposing ◽

Experimental Drugs ◽

Experimental Drug ◽

Investigational Drugs ◽

Approved Drugs ◽

Fda Approved Drugs ◽

SARS-CoV-2 is the seventh coronavirus that is reported to cause infection in Homo sapiens. Considering its pandemic nature, development of newer and effective therapeutic strategies, drug repurposing in combination with target validation approaches has led to the identification of new antiviral molecules. In current work, we performed virtual screening and molecular docking of 8548 ligands on target protein coronavirus endoribonuclease NendoU (6VWW). The molecules selected includes FDA approved drugs along with investigational or experimental drugs recommended for anticancer, antiviral, antimicrobial, and antiprotozoal properties. The thorough selection and their rationality with Covid-19 led us to propose that FDA approved drug DB00876 (Eprosartan), Investigational drugs DB15063 (Inarigivir soproxil), DB12307 (Foretinib) and DB01813 an experimental drug may be repurposed for treatment of Covid-19 disease.

Selection of Active Antiviral Compounds Against Covid-19 Disease Targeting Coronavirus Endoribonuclease Nendou/NSP15 Via Ligand- Based Virtual Screening and Molecular Docking

Letters in Drug Design & Discovery ◽

10.2174/1570180817999201211191445 ◽

2020 ◽

Vol 17 ◽

Author(s):

Gaurav Joshi ◽

Ramarao Poduri

Keyword(s):

Virtual Screening ◽

Drug Repurposing ◽

Antiviral Compounds ◽

Clinical Level ◽

Rapid Spread ◽

Approved Drugs ◽

Fda Approved Drugs ◽

Background: The rapid spread of SARS-CoV-2 has caused havoc and panic among individuals, which has further worsened due to the unavailability of a proven drug(s) regime. Objective: The current work involves drug repurposing from the pool of USFDA approved drugs involving in silico virtual screening technique against Covid-19. Methods: Methodology involves virtual screening of 8548 FDA approved drugs against target protein endoribonuclease NendoU (Nsp15) (PDB ID: 6VWW). Results: Virtual screening-based analysis enabled us to identify four drugs, Eprosartan, Inarigivir soproxil, Foretinib, and DB01813 that could plausibly target Nsp15 against Covid-19 disease. Conclusion: The work offers the scope to corroborate the findings via in vitro and in vivo techniques to identify the potential of selected leads against Covid-19. The outcome may also help in tracing their molecular mechanism(s) in addition to their development at the clinical level in the future.

In silico drug repurposing of FDA-approved drugs to predict new inhibitors for drug resistant T315I mutant and wild-type BCR-ABL1: A virtual screening and molecular dynamics study

Journal of Molecular Graphics and Modelling ◽

10.1016/j.jmgm.2017.04.005 ◽

2017 ◽

Vol 74 ◽

pp. 234-240 ◽

Cited By ~ 7

Author(s):

Farzin Sohraby ◽

Milad Bagheri ◽

Masoud Aliyar ◽

Hassan Aryapour

Keyword(s):

Molecular Dynamics ◽

Virtual Screening ◽

In Silico ◽

Drug Repurposing ◽

Drug Resistant ◽

Wild Type ◽

Approved Drugs ◽

Thiazole Compounds as Antiviral Agents: An Update

Medicinal Chemistry ◽

10.2174/1573406415666190614101253 ◽

2020 ◽

Vol 16 (1) ◽

pp. 4-23 ◽

Cited By ~ 8

Author(s):

Inder P. Singh ◽

Shiv Gupta ◽

Sanjay Kumar

Keyword(s):

Biological Activities ◽

Relevant Literature ◽

Antiviral Agents ◽

Experimental Drugs ◽

Patent Literature ◽

Antiviral Activities ◽

Approved Drugs ◽

Fda Approved Drugs ◽

Anti Hiv ◽

Hiv 1

Background: Thiazole is a good nucleus owing to its various pharmaceutical applications. Thiazole containing compounds (thiazoles) have shown various biological activities like antioxidant, analgesic, antibacterial, anticancer, antiallergic, antihypertensive, antiinflammatory, antimalarial, antifungal and antipsychotic. The scaffold is present in more than 18 FDA approved drugs and also in more than 70 experimental drugs. Only a few reviews are available in the literature despite its great medicinal importance. During the course of time, this scaffold has been studied extensively for its antiviral activities and provided compounds with activity in the nM range. However, no focused review is available on the compilation of antiviral activities shown by this scaffold. Objective: In the present review, we have made an effort to compile antiviral literature of thiazoles reported from the year 2011 to till date. Methods: We searched the SciFinder database (excluding patent literature) with keywords like “antiviral”, “anti-HIV” and “virus”. Further filters were applied for the year of publication and keywords thiazole, reviews etc. to find relevant literature reported on the antiviral activities of thiazoles. Results: Nearly, 50 research articles were selected to compile and review the antiviral literature of thiazoles reported from the year 2011 to till date. Compounds 8, 25, 40, 62, 72, 73, 91, 112, 113, 131, 137, 175, 198, 200, 201 and 213 were reported in the literature with potent antiviral activity against CVB, SARS, RSV, HCV, HRV, VZV, TMV, FMDV, DENV, YFV, influenza virus, Junin virus, HIV-1, HSV, VV and EBV, respectively. Conclusion: There is further scope for the synthesis and evaluation of novel thiazole compounds by taking the most active compounds as lead structures. In conclusion, this review provides an overview of antiviral activities of thiazole compounds reported from the year 2011 to till date.

Virtual Screening of Potential Drug Molecules Against Covid-19 Targets: A Drug Repurposing Approach

Letters in Applied NanoBioScience ◽

10.33263/lianbs111.29652980 ◽

2021 ◽

Vol 11 (1) ◽

pp. 2965-2980

Keyword(s):

Virtual Screening ◽

Drug Repurposing ◽

Structural Protein ◽

Drug Molecules ◽

Main Protease ◽

The World ◽

Nelfinavir Mesylate ◽

Tenofovir Alafenamide ◽

Approved Drugs ◽

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shattered normal life across the world. This deadly virus displays many variants and has claimed many lives in various countries. Spike protein plays a major role in the transmission and infectivity of this virus. The scientific community is trying hard to reign this virus and save human lives. In this effort, drug repurposing has emerged as a reliable tool to screen FDA-approved drugs. In the present study, we did a virtual screening of 265 FDA-approved drugs against two important covid-19 targets (Non-structural protein & main protease) with PDB IDs 6W4H, 6LU7, and 6W63. A comparative analysis of the best drugs based on docking score, binding energy, and effective hits was done against both targets. Out of 265 molecules, the best 7 molecules showed reliable hits against both targets. Best seven drugs namely Saquinavir, Indinavir, Tenofovir Alafenamide, Ritonavir, Nelfinavir mesylate, Cefiderocol and Plazomicin. Our results suggest that these ligands, in combination or individually, can be taken as novel prospects for developing a drug against SARS CoV-2.

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 ◽

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 ◽

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.

Thiazole Ring—A Biologically Active Scaffold

Molecules ◽

10.3390/molecules26113166 ◽

2021 ◽

Vol 26 (11) ◽

pp. 3166

Author(s):

Anthi Petrou ◽

Maria Fesatidou ◽

Athina Geronikaki

Keyword(s):

Recent Literature ◽

Biological Activities ◽

Literature Survey ◽

Biologically Active ◽

Thiazole Ring ◽

Peer Reviews ◽

Experimental Drugs ◽

Wide Range ◽

Approved Drugs ◽

Background: Thiazole is a good pharmacophore nucleus due to its various pharmaceutical applications. Its derivatives have a wide range of biological activities such as antioxidant, analgesic, and antimicrobial including antibacterial, antifungal, antimalarial, anticancer, antiallergic, antihypertensive, anti-inflammatory, and antipsychotic. Indeed, the thiazole scaffold is contained in more than 18 FDA-approved drugs as well as in numerous experimental drugs. Objective: To summarize recent literature on the biological activities of thiazole ring-containing compounds Methods: A literature survey regarding the topics from the year 2015 up to now was carried out. Older publications were not included, since they were previously analyzed in available peer reviews. Results: Nearly 124 research articles were found, critically analyzed, and arranged regarding the synthesis and biological activities of thiazoles derivatives in the last 5 years.