A Review on Drug Repurposing: A Strategy to Treat Human Coronavirus Disease (COVID-19)

2020 ◽  
pp. 42-54
Author(s):  
Neetu Bhattacharya ◽  
Shashank Kumar Maurya ◽  
Sabyasachi Senapati ◽  
Amit Bhattacharya
Keyword(s):  
Indian Subcontinent ◽  
Drug Repurposing ◽  
Controlled Clinical Trials ◽  
Wuhan City ◽  
Human Coronavirus ◽  
Plasma Therapy ◽  
Mass Immunization ◽  
Place Of Origin ◽  
Repurposed Drugs ◽  
Novel Coronavirus

Novel coronavirus pandemic has created a massive public health emergency causing around 1.85 million deaths world-wide till 5th January, 2021. New SARS (Severe Acute Respiratory Syndrome) coronavirus strain known as SARS-CoV-2 is the causative agent which infected more than 84 million people across the globe. Current epicentre of the pandemic has shifted to Europe and United States and Indian subcontinent from its place of origin-Wuhan City, Hubei province in China. Due to limited availability of vaccines against SARS-CoV-2 or its related β-coronavirus (SARS-CoV or MERS-CoV), mass immunization is currently not possible. Thus, use of curative therapies could be the only choice of intervention. Therefore, rapid treatment of millions of COVID-19 patients in limited time can only be achieved by repurposing pre-approved and existing drugs. Network-based high-throughput computational approach has also predicted several repurposable drugs. Cheaper, less toxic and well tolerated drugs such as antimalarial drugs: Chloroquine (CQ) & Hydroxychloroquine (HCQ); antiviral drugs: Remdesivir, Lopinavir and Ritonavir are among many others that have been proposed for the COVID-19 treatment. Presently limited controlled clinical trials are underway to assess the therapeutic outcome of these repurposed drugs along with novel candidate vaccines and medicines. Beside these, convalescent plasma therapy has also emerged as potential therapeutic approach being tested in several countries. This review focuses on few of the promising repurposed drugs and their outcomes that are presently under evaluation for their safety and efficacy against the coronavirus disease 2019 (COVID-19).

scholarly journals Resveratrol Inhibits HCoV-229E and SARS-CoV-2 Coronavirus Replication In Vitro

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 354
Author(s):  
Sébastien Pasquereau ◽  
Zeina Nehme ◽  
Sandy Haidar Ahmad ◽  
Fadoua Daouad ◽  
Jeanne Van Assche ◽  
...  
Keyword(s):  
Drug Repurposing ◽  
Effective Concentration ◽  
Selectivity Index ◽  
Viral Titer ◽  
Human Coronavirus ◽  
Candidate Drug ◽  
Drug Compounds ◽  
Low Cytotoxicity ◽  
Novel Coronavirus

A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in China at the end of 2019 causing a large global outbreak. As treatments are of the utmost importance, drug repurposing embodies a rich and rapid drug discovery landscape, where candidate drug compounds could be identified and optimized. To this end, we tested seven compounds for their ability to reduce replication of human coronavirus (HCoV)-229E, another member of the coronavirus family. Among these seven drugs tested, four of them, namely rapamycin, disulfiram, loperamide and valproic acid, were highly cytotoxic and did not warrant further testing. In contrast, we observed a reduction of the viral titer by 80% with resveratrol (50% effective concentration (EC50) = 4.6 µM) and lopinavir/ritonavir (EC50 = 8.8 µM) and by 60% with chloroquine (EC50 = 5 µM) with very limited cytotoxicity. Among these three drugs, resveratrol was less cytotoxic (cytotoxic concentration 50 (CC50) = 210 µM) than lopinavir/ritonavir (CC50 = 102 µM) and chloroquine (CC50 = 67 µM). Thus, among the seven drugs tested against HCoV-229E, resveratrol demonstrated the optimal antiviral response with low cytotoxicity with a selectivity index (SI) of 45.65. Similarly, among the three drugs with an anti-HCoV-229E activity, namely lopinavir/ritonavir, chloroquine and resveratrol, only the latter showed a reduction of the viral titer on SARS-CoV-2 with reduced cytotoxicity. This opens the door to further evaluation to fight Covid-19.

scholarly journals An Update on Antiviral Therapy Against SARS-CoV-2: How Far Have We Come?

2021 ◽  
Vol 12 ◽  
Author(s):  
Omkar Indari ◽  
Shweta Jakhmola ◽  
Elangovan Manivannan ◽  
Hem Chandra Jha
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Drug Repurposing ◽  
Clinical Findings ◽  
Open Label ◽  
Plasma Therapy ◽  
Clinical Safety ◽  
Treatment Research ◽  
Repurposed Drugs ◽  
Approved Drugs

COVID-19 pandemic has spread worldwide at an exponential rate affecting millions of people instantaneously. Currently, various drugs are under investigation to treat an enormously increasing number of COVID-19 patients. This dreadful situation clearly demands an efficient strategy to quickly identify drugs for the successful treatment of COVID-19. Hence, drug repurposing is an effective approach for the rapid discovery of frontline arsenals to fight against COVID-19. Successful application of this approach has resulted in the repurposing of some clinically approved drugs as potential anti-SARS-CoV-2 candidates. Several of these drugs are either antimalarials, antivirals, antibiotics or corticosteroids and they have been repurposed based on their potential to negate virus or reduce lung inflammation. Large numbers of clinical trials have been registered to evaluate the effectiveness and clinical safety of these drugs. Till date, a few clinical studies are complete and the results are primary. WHO also conducted an international, multi-country, open-label, randomized trials-a solidarity trial for four antiviral drugs. However, solidarity trials have few limitations like no placebos were used, additionally any drug may show effectiveness for a particular population in a region which may get neglected in solidarity trial analysis. The ongoing randomized clinical trials can provide reliable long-term follow-up results that will establish both clinical safety and clinical efficacy of these drugs with respect to different regions, populations and may aid up to worldwide COVID-19 treatment research. This review presents a comprehensive update on majorly repurposed drugs namely chloroquine, hydroxychloroquine, remdesivir, lopinavir-ritonavir, favipiravir, ribavirin, azithromycin, umifenovir, oseltamivir as well as convalescent plasma therapy used against SARS-CoV-2. The review also summarizes the data recorded on the mechanism of anti-SARS-CoV-2 activity of these repurposed drugs along with the preclinical and clinical findings, therapeutic regimens, pharmacokinetics, and drug-drug interactions.

Drug Repurposing Studies Targeting SARS-nCoV2: An Ensemble Docking Approach on Drug Target 3C-like Protease (3CLpro)

2020 ◽  
Author(s):  
Shruti Koulgi ◽  
Vinod Jani ◽  
Mallikarjunachari Uppuladinne ◽  
Uddhavesh Sonavane ◽  
Asheet Kumar Nath ◽  
...  
Keyword(s):  
Drug Repurposing ◽  
Drug Binding ◽  
Ensemble Docking ◽  
Drug Molecules ◽  
Drug Binding Site ◽  
Main Protease ◽  
Docking Approach ◽  
Novel Coronavirus ◽  
Markov State Modeling ◽  
Viral Polyprotein

<p>The COVID-19 pandemic has been responsible for several deaths worldwide. The causative agent behind this disease is the Severe Acute Respiratory Syndrome – novel Coronavirus 2 (SARS-nCoV2). SARS-nCoV2 belongs to the category of RNA viruses. The main protease, responsible for the cleavage of the viral polyprotein is considered as one of the hot targets for treating COVID-19. Earlier reports suggest the use of HIV anti-viral drugs for targeting the main protease of SARS-CoV, which caused SARS in the year 2002-03. Hence, drug repurposing approach may prove to be useful in targeting the main protease of SARS-nCoV2. The high-resolution crystal structure of 3CL<sup>pro</sup> (main protease) of SARS-nCoV2 (PDB ID: 6LU7) was used as the target. The Food and Drug Administration (FDA) approved and SWEETLEAD database of drug molecules were screened. The apo form of the main protease was simulated for a cumulative of 150 ns and 10 μs open source simulation data was used, to obtain conformations for ensemble docking. The representative structures for docking were selected using RMSD-based clustering and Markov State Modeling analysis. This ensemble docking approach for main protease helped in exploring the conformational variation in the drug binding site of the main protease leading to efficient binding of more relevant drug molecules. The drugs obtained as best hits from the ensemble docking possessed anti-bacterial and anti-viral properties. Small molecules with these properties may prove to be useful to treat symptoms exhibited in COVID-19. This <i>in-silico</i> ensemble docking approach would support identification of potential candidates for repurposing against COVID-19.</p>

Treatment Options in COVID-19: The Role of Bioavailable Antiviral Ribonucleoside Analog on NHC in vitro

2020 ◽  
Author(s):  
Lara Bittmann
Keyword(s):  
World Health Organization ◽  
Clinical Picture ◽  
Treatment Options ◽  
World Health ◽  
Wuhan City ◽  
The World ◽  
Novel Coronavirus ◽  
Health Organization

On December 31, 2019, WHO was informed of cases of pneumonia of unknown cause in Wuhan City, China. A novel coronavirus was identified as the cause by Chinese authorities on January 7, 2020 and was provisionally named "2019-nCoV". This new Coronavirus causes a clinical picture which has received now the name COVID-19. The virus has spread subsequently worldwide and was explained on the 11th of March, 2020 by the World Health Organization to the pandemic.

The Antiviral and Antimalarial Drug Repurposing in Quest of Chemotherapeutics to Combat COVID-19 Utilizing Structure-Based Molecular Docking

2020 ◽  
Vol 23 ◽  
Author(s):  
Sisir Nandi ◽  
Mohit Kumar ◽  
Mridula Saxena ◽  
Anil Kumar Saxena
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Drug Repurposing ◽  
Clinical Settings ◽  
The Novel ◽  
In Silico Docking ◽  
Biochemical Mechanisms ◽  
Novel Coronavirus ◽  
In Silico Molecular Docking

Background: The novel coronavirus disease (COVID-19) is caused by a new strain (SARS-CoV-2) erupted in 2019. Nowadays, it is a great threat that claims uncountable lives worldwide. There is no specific chemotherapeutics developed yet to combat COVID-19. Therefore, scientists have been devoted in the quest of the medicine that can cure COVID- 19. Objective: Existing antivirals such as ASC09/ritonavir, lopinavir/ritonavir with or without umifenovir in combination with antimalarial chloroquine or hydroxychloroquine have been repurposed to fight the current coronavirus epidemic. But exact biochemical mechanisms of these drugs towards COVID-19 have not been discovered to date. Method: In-silico molecular docking can predict the mode of binding to sort out the existing chemotherapeutics having a potential affinity towards inhibition of the COVID-19 target. An attempt has been made in the present work to carry out docking analyses of 34 drugs including antivirals and antimalarials to explain explicitly the mode of interactions of these ligands towards the COVID-19protease target. Results: 13 compounds having good binding affinity have been predicted towards protease binding inhibition of COVID-19. Conclusion: Our in silico docking results have been confirmed by current reports from clinical settings through the citation of suitable experimental in vitro data available in the published literature.

Can Mandated BCG Vaccine Promote herd Immunity against Novel Coronavirus? A Potential Solution at Hand to Tackle Covid-19 Pandemic

2020 ◽  
Vol 16 (1) ◽  
pp. 6-11
Author(s):  
Ashok Arasu ◽  
Pavithra Balakrishnan ◽  
Thirunavukkarasu Velusamy ◽  
Thiagarajan Ramesh
Keyword(s):  
Protective Factor ◽  
Herd Immunity ◽  
Bcg Vaccine ◽  
Intestinal Cells ◽  
Global Public Health ◽  
Wuhan City ◽  
Live Attenuated Vaccine ◽  
Angiotensin Converting Enzyme 2 ◽  
Lung Epithelial ◽  
Novel Coronavirus

The 2019 novel coronavirus (2019-nCoV) infection is an emerging pandemic that poses a severe threat to global public health. This pandemic started from the Wuhan City of Hubei Province in China, and is speculated to have originated from bats and spread among humans with an unknown intermediate transmitter. The virus binds to angiotensin-converting enzyme 2 (ACE2), which is abundantly expressed on various human cells, including lung epithelial and intestinal cells, thereby entering into these cells and causing infection. It is transmitted to other humans through airborne droplets from infected patients. Presently there are no specific treatments or vaccines that are available to curtail the spread of this disease. There are few indirect reports that explain the potential importance of the mandated BCG vaccine as a protective factor against COVID-19. There is a speculation that a live attenuated vaccine (BCG vaccine) can be beneficial against COVID-19 to develop the initial immune response, and can also spread in the community, thereby boosting herd immunity to fight against COVID-19. This review summarizes the conclusions of various reports on the BCG vaccine, and is an attempt to establish BCG-vaccination mediated herd immunity as an effective instant intermediate approach in curbing COVID-19 spread in highly populous countries.

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.

Determination of binding potential of HCV protease inhibitors against SARS-CoV-2 Papain-like protease with computational docking

2021 ◽  
Vol 18 ◽  
Author(s):  
Zihni Onur Çalışkaner
Keyword(s):  
Protease Inhibitors ◽  
Drug Repurposing ◽  
Docking Study ◽  
Binding Energies ◽  
Binding Potential ◽  
Computational Docking ◽  
In Silico Docking ◽  
Hcv Protease ◽  
Novel Coronavirus ◽  
Inhibitory Molecules

Background: SARS-CoV-2, a novel coronavirus that causes a pandemic respiratory disease, has recently emerged from China. Since it’s a life-threatening virus, investigation of curative medications along with protective vaccines still maintains its importance. Drug repurposing is a reasonable and immediate approach to combat SARS-CoV-2 infection by identifying inhibitory molecules from marketed drugs. PL protease (PLpro.) is one of the essential enzymes for the progression of SARS-CoV-2 replication and life cycle. Objective: We aimed to investigate the potential of 4 HCV protease inhibitors as probable repurposing drugs in Covid-19 treatment. Methods: In order to understand the possible binding affinity of HCV protease inhibitors, Boceprevir, Grazoprevir, Simeprevir, and Telaprevir, against to PLpro, we performed docking analysis in silico. Docking study was accomplished using AutoDock 4.2 software. Potential druggable pockets on PLpro were predicted by DoGSiteScorer tool in order to explore any overlapping with binding regions and these pockets. Results: This analysis demonstrated Boceprevir, Grazoprevir, Simeprevir and Telaprevir interacted by PLpro with binding energies (kcal/mol) of -4.97, -4.24, -6.98, -1.08, respectively. Asn109, one of the interacted residues with both Boceprevir and Simeprevir, is a neighbouring residue to catalytic Cys111. Additionally, Telaprevir notably interacted with catalytic His272 in the active site. Conclusion: Present study explains the binding efficiency and repurposing potential of certain HCV protease inhibitors against to SARS-CoV-2 PLpro enzyme. Docking sites and potential druggability of ligands were also crosschecked by the estimation of druggable pockets. Thereby our results can promote promising preliminary data for research on drug development in the fight of Covid-19.

scholarly journals Potential 2019-nCoV 3C-like Protease Inhibitors Designed Using Generative Deep Learning Approaches

2020 ◽  
Author(s):  
Alex Zhavoronkov ◽  
Vladimir Aladinskiy ◽  
Alexander Zhebrak ◽  
Bogdan Zagribelnyy ◽  
Victor Terentiev ◽  
...  
Keyword(s):  
Homology Modelling ◽  
Drug Repurposing ◽  
Hiv Protease ◽  
Learning Approaches ◽  
Protein Targets ◽  
Chemical Libraries ◽  
Internal Resources ◽  
Novel Coronavirus ◽  
Approved Drugs ◽  
Novel Drug

<div> <div> <div> <p>The emergence of the 2019 novel coronavirus (2019-nCoV), for which there is no vaccine or any known effective treatment created a sense of urgency for novel drug discovery approaches. One of the most important 2019-nCoV protein targets is the 3C-like protease for which the crystal structure is known. Most of the immediate efforts are focused on drug repurposing of known clinically-approved drugs and virtual screening for the molecules available from chemical libraries that may not work well. For example, the IC50 of lopinavir, an HIV protease inhibitor, against the 3C-like protease is approximately 50 micromolar. In an attempt to address this challenge, on January 28th, 2020 Insilico Medicine decided to utilize a part of its generative chemistry pipeline to design novel drug-like inhibitors of 2019-nCoV and started generation on January 30th. It utilized three of its previously validated generative chemistry approaches: crystal-derived pocked- based generator, homology modelling-based generation, and ligand-based generation. Novel druglike compounds generated using these approaches are being published at www.insilico.com/ncov-sprint/ and will be continuously updated. Several molecules will be synthesized and tested using the internal resources; however, the team is seeking collaborations to synthesize, test, and, if needed, optimize the published molecules. </p> </div> </div> </div>

scholarly journals Early epidemiological assessment of the transmission potential and virulence of coronavirus disease 2019 (COVID-19) in Wuhan City: China, January-February, 2020

2020 ◽  
Author(s):  
Kenji Mizumoto ◽  
Katsushi Kagaya ◽  
Gerardo Chowell
Keyword(s):  
Basic Reproduction Number ◽  
Reproduction Number ◽  
Public Health Intervention ◽  
Ecological Modelling ◽  
The Novel ◽  
Wuhan City ◽  
Transmission Potential ◽  
The World ◽  
Novel Coronavirus ◽  
Epidemiological Parameters

AbstractBackgroundSince the first cluster of cases was identified in Wuhan City, China, in December, 2019, coronavirus disease 2019 (COVID-19) rapidly spread around the world. Despite the scarcity of publicly available data, scientists around the world have made strides in estimating the magnitude of the epidemic, the basic reproduction number, and transmission patterns. Accumulating evidence suggests that a substantial fraction of the infected individuals with the novel coronavirus show little if any symptoms, which highlights the need to reassess the transmission potential of this emerging disease. In this study, we derive estimates of the transmissibility and virulence of COVID-19 in Wuhan City, China, by reconstructing the underlying transmission dynamics using multiple data sources.MethodsWe employ statistical methods and publicly available epidemiological datasets to jointly derive estimates of transmissibility and severity associated with the novel coronavirus. For this purpose, the daily series of laboratory–confirmed COVID-19 cases and deaths in Wuhan City together with epidemiological data of Japanese repatriated from Wuhan City on board government–chartered flights were integrated into our analysis.ResultsOur posterior estimates of basic reproduction number (R) in Wuhan City, China in 2019–2020 reached values at 3.49 (95%CrI: 3.39–3.62) with a mean serial interval of 6.0 days, and the enhanced public health intervention after January 23rd in 2020 was associated with a significantly reduced R at 0.84 (95%CrI: 0.81–0.88), with the total number of infections (i.e. cumulative infections) estimated at 1906634 (95%CrI: 1373500–2651124) in Wuhan City, elevating the overall proportion of infected individuals to 19.1% (95%CrI: 13.5–26.6%). We also estimated the most recent crude infection fatality ratio (IFR) and time–delay adjusted IFR at 0.04% (95% CrI: 0.03%–0.06%) and 0.12% (95%CrI: 0.08–0.17%), respectively, estimates that are several orders of magnitude smaller than the crude CFR estimated at 4.06%ConclusionsWe have estimated key epidemiological parameters of the transmissibility and virulence of COVID-19 in Wuhan, China during January-February, 2020 using an ecological modelling approach. The power of this approach lies in the ability to infer epidemiological parameters with quantified uncertainty from partial observations collected by surveillance systems.

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