scholarly journals Identification of potential inhibitors of SARS-COV-2 endoribonuclease (EndoU) from FDA approved drugs: a drug repurposing approach to find therapeutics for COVID-19

Author(s):  
Anshuman Chandra ◽  
Vaishali Gurjar ◽  
Imteyaz Qamar ◽  
Nagendra Singh
2020 ◽  
Author(s):  
Bello Martiniano ◽  
Martínez-Muñoz Alberto ◽  
Balbuena-Rebolledo Irving

Abstract Among targets selected for studies aimed to identify potential inhibitors against COVID-19, SARS-CoV2 main proteinase (Mpro) is highlighted. Mpro is indispensable for virus replication, and is a promising target of potential inhibitors of COVID-19. Recently, monomeric SARS-CoV2 Mpro, drug repurposing and docking methods have facilitated the identification of several potential inhibitors. Results were refined through the assessment of dimeric SARS-CoV2 Mpro, which represents the functional state of enzyme. Docking and molecular dynamics (MD) simulations combined with molecular mechanics/generalized Born surface area (MM/GBSA) studies indicated that dimeric Mpro most significantly impacts binding affinity tendency compared with the monomeric state, which suggesting that dimeric state is most useful when performing studies aimed to identify drugs targeting Mpro. In this study, we extend previous research by performing docking and MD simulation studies coupled with an MM/GBSA approach to assess binding of dimeric SARS-CoV2 Mpro to 12 FDA-approved drugs (darunavir, indinavir, saquinavir, tipranavir, diosmin, hesperidin, rutin, raltegravir, velpatasvir, ledipasvir, rosuvastatin and bortezomib), which were identified as the best candidates for treatment of COVID-19 in some previous dockings studies involving monomeric SARS-CoV2 Mpro. This analysis identified saquinavir as a potent inhibitor of dimeric SARS-CoV2 Mpro, therefore, the compound may have clinical utility against COVID-19.


2018 ◽  
Vol 14 (2) ◽  
pp. 106-116 ◽  
Author(s):  
Olujide O. Olubiyi ◽  
Maryam O. Olagunju ◽  
James O. Oni ◽  
Abidemi O. Olubiyi

Antibiotics ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 40
Author(s):  
David Gur ◽  
Theodor Chitlaru ◽  
Emanuelle Mamroud ◽  
Ayelet Zauberman

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.


2019 ◽  
pp. 625-648 ◽  
Author(s):  
Carolina L. Belllera ◽  
María L. Sbaraglini ◽  
Lucas N. Alberca ◽  
Juan I. Alice ◽  
Alan Talevi

Viruses ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1325
Author(s):  
Yoonjung Choi ◽  
Bonggun Shin ◽  
Keunsoo Kang ◽  
Sungsoo Park ◽  
Bo Ram Beck

Previously, our group predicted commercially available Food and Drug Administration (FDA) approved drugs that can inhibit each step of the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using a deep learning-based drug-target interaction model called Molecule Transformer-Drug Target Interaction (MT-DTI). Unfortunately, additional clinically significant treatment options since the approval of remdesivir are scarce. To overcome the current coronavirus disease 2019 (COVID-19) more efficiently, a treatment strategy that controls not only SARS-CoV-2 replication but also the host entry step should be considered. In this study, we used MT-DTI to predict FDA approved drugs that may have strong affinities for the angiotensin-converting enzyme 2 (ACE2) receptor and the transmembrane protease serine 2 (TMPRSS2) which are essential for viral entry to the host cell. Of the 460 drugs with Kd of less than 100 nM for the ACE2 receptor, 17 drugs overlapped with drugs that inhibit the interaction of ACE2 and SARS-CoV-2 spike reported in the NCATS OpenData portal. Among them, enalaprilat, an ACE inhibitor, showed a Kd value of 1.5 nM against the ACE2. Furthermore, three of the top 30 drugs with strong affinity prediction for the TMPRSS2 are anti-hepatitis C virus (HCV) drugs, including ombitasvir, daclatasvir, and paritaprevir. Notably, of the top 30 drugs, AT1R blocker eprosartan and neuropsychiatric drug lisuride showed similar gene expression profiles to potential TMPRSS2 inhibitors. Collectively, we suggest that drugs predicted to have strong inhibitory potencies to ACE2 and TMPRSS2 through the DTI model should be considered as potential drug repurposing candidates for COVID-19.


2019 ◽  
Vol 26 (28) ◽  
pp. 5363-5388 ◽  
Author(s):  
Ananda Kumar Konreddy ◽  
Grandhe Usha Rani ◽  
Kyeong Lee ◽  
Yongseok Choi

: Drug repurposing is a safe and successful pathway to speed up the novel drug discovery and development processes compared with de novo drug discovery approaches. Drug repurposing uses FDA-approved drugs and drugs that failed in clinical trials, which have detailed information on potential toxicity, formulation, and pharmacology. Technical advancements in the informatics, genomics, and biological sciences account for the major success of drug repurposing in identifying secondary indications of existing drugs. Drug repurposing is playing a vital role in filling the gap in the discovery of potential antibiotics. Bacterial infections emerged as an ever-increasing global public health threat by dint of multidrug resistance to existing drugs. This raises the urgent need of development of new antibiotics that can effectively fight multidrug-resistant bacterial infections (MDRBIs). The present review describes the key role of drug repurposing in the development of antibiotics during 2016–2017 and of the details of recently FDA-approved antibiotics, pipeline antibiotics, and antibacterial properties of various FDA-approved drugs of anti-cancer, anti-fungal, anti-hyperlipidemia, antiinflammatory, anti-malarial, anti-parasitic, anti-viral, genetic disorder, immune modulator, etc. Further, in view of combination therapies with the existing antibiotics, their potential for new implications for MDRBIs is discussed. The current review may provide essential data for the development of quick, safe, effective, and novel antibiotics for current needs and suggest acuity in its effective implications for inhibiting MDRBIs by repurposing existing drugs.


2021 ◽  
Vol 10 (4) ◽  
pp. 2766-2776

Diabetes mellitus is considered a global epidemic disease and is one of the metabolic diseases affecting individuals irrespective of age, sex, and race. According to WHO epidemiology data, the DM prevalence globally has risen from 4.7% to 8.5 % from 1980 to 2014. The discovery of new drugs has become more challenging for the pharmaceutical companies even though major investment has made in the conventional drug discovery approach. To overcome this obstacle, drug repurposing is an emerging field of development where an existing drug is tested for treatment. Successful repurposing of zidovudine, minoxidil, sildenafil, celecoxib, aspirin, and topiramate are reported for respective diseases. The present study focused on the computational approach to fetch the favorable drugs from the pool of FDA approved drugs against diabetes. Initially, structure similarity studies were carried out by using the template structure of standard DPP-IV inhibitor, Linagliptin. About 26 drugs have shown similarity, and the other 14 drugs filtered by Pass Online binding energies are determined by molecular docking at the binding site of DPP-IV (PDB ID 2i78). Among these, pranlukast and mirabegron have shown good binding interactions with dock scores of -13.81 and -13.06.


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