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1.
Frontiers in molecular biosciences ; 9, 2022.
Article in English | EuropePMC | ID: covidwho-1863974

ABSTRACT

The ongoing pandemic coronavirus disease (COVID-19) caused by a novel corona virus, namely, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has had a major impact on global public health. COVID-19 cases continue to increase across the globe with high mortality rates in immunocompromised patients. There is still a pressing demand for drug discovery and vaccine development against this highly contagious disease. To design and develop antiviral drugs against COVID-19, the main protease (Mpro) has emerged as one of the important drug targets. In this context, the present work explored Jadwar (Delphinium denudatum)–derived natural alkaloids as potential inhibitors against Mpro of SARS-CoV-2 by employing a combination of molecular docking and molecular dynamic simulation–based methods. Molecular docking and interaction profile analysis revealed strong binding on the Mpro functional domain with four natural alkaloids viz. panicutine (−7.4 kcal/mol), vilmorrianone (−7.0 kcal/mol), denudatine (−6.0 kcal/mol), and condelphine (−5.9 kcal/mol). The molecular docking results evaluated by using the MD simulations on 200 nanoseconds confirmed highly stable interactions of these compounds with the Mpro. Additionally, mechanics/generalized Born/Poisson–Boltzmann surface area (MM/G/P/BSA) free energy calculations also affirmed the docking results. Natural alkaloids explored in the present study possess the essential drug-likeness properties, namely, absorption, distribution, metabolism, and excretion (ADME), and are in accordance with Lipinski’s rule of five. The results of this study suggest that these four bioactive molecules, namely, condelphine, denudatine, panicutine, and vilmorrianone, might be effective candidates against COVID-19 and can be further investigated using a number of experimental methods.

2.
Journal of Statistics and Management Systems ; : 1-18, 2022.
Article in English | Taylor & Francis | ID: covidwho-1784166
3.
Microb Pathog ; 168: 105512, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1768412

ABSTRACT

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is an illness caused by the new coronavirus severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). It has affected public health and the economy globally. Currently approved vaccines and other drug candidates could be associated with several drawbacks which urges developing alternative therapeutic approaches. AIM: To provide a comprehensive review of anti-SARS-CoV-2 activities of plants and their bioactive compounds. METHODS: Information was gathered from diverse bibliographic platforms such as PubMed, Google Scholar, and ClinicalTrials.gov registry. RESULTS: The present review highlights the potential roles of crude extracts of plants as well as plant-derived small molecules in inhibiting SARS-CoV-2 infection by targeting viral or host factors essential for viral entry, polyprotein processing, replication, assembly and release. Their anti-inflammatory and antioxidant properties as well as plant-based therapies that are under development in the clinical trial phases-1 to 3 are also covered. CONCLUSION: This knowledge could further help understanding SARS-CoV-2 infection and anti-viral mechanisms of plant-based therapeutics.


Subject(s)
COVID-19 , SARS-CoV-2 , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Humans , Virus Internalization
4.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-317117

ABSTRACT

COVID-19 pandemic has now expanded over 213 nations across the world. To date, there is no specific medication available for SARS CoV-2 infection. The main protease (M pro ) of SARS CoV-2 plays a crucial role in viral replication and transcription and thereby considered as an attractive drug target for the inhibition of COVID-19,. Natural compounds are widely recognised as valuabe source of antiviral drugs due to their structural diversity and safety. In the current study, we have screened twenty natural compounds having antiviral properties to discover the potential inhibitor molecules against M pro of COVID-19. Systematic molecular docking analysis was conducted using AuroDock 4.2 to determine the binding affinities and interactions between natural compounds and the M pro . Out of twenty molecules, four natural metabolites namely, amentoflavone, guggulsterone, puerarin, and piperine were found to have strong interaction with M pro of COVID-19 based on the docking analysis. These selected natural compounds were further validated using combination of molecular dynamic simulations and molecular mechanic/generalized/Born/Poisson-Boltzmann surface area (MM/G/P/BSA) free energy calculations. During MD simulations, all four natural compounds bound to M pro on 50ns and MM/G/P/BSA free energy calculations showed that all four shortlisted ligands have stable and favourable energies causing strong binding with binding site of M pro protein. These four natural compounds have passed the Absorption, Distribution, Metabolism, and Excretion (ADME) property as well as Lipinski’s rule of five. Our promising findings based on in-silico studies warrant further clinical trials in order to use these natural compounds as potential inhibitors of M pro protein of COVID.

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-314621

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel corona virus that causes corona virus disease 2019 (COVID-19). The COVID-19 rapidly spread across the nations with high mortality rate even as very little is known to contain the virus at present. In the current study, we report novel natural metabolites namely, ursolic acid, carvacrol and oleanolic acid as the potential inhibitors against main protease (M pro ) of COVID-19 by using integrated molecular modeling approaches. From a combination of molecular docking and molecular dynamic (MD) simulations, we found three ligands bound to protease during 50 ns of MD simulations. Furthermore, the molecular mechanic/generalized/Born/Poisson-Boltzmann surface area (MM/G/P/BSA) free energy calculations showed that these chemical molecules have stable and favourable energies causing strong binding with binding site of M pro protein. All these three molecules, namely, ursolic acid, carvacrol and oleanolic acid, have passed the ADME (Absorption, Distribution, Metabolism, and Excretion) property as well as Lipinski’s rule of five. The study provides a basic foundation and suggests that the three phytochemicals, viz. ursolic acid, carvacrol and oleanolic acid could serve as potential inhibitors in regulating the M pro protein's function and controlling viral replication.

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-311682

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease2019 (COVID-19). SARS-CoV-2 is known for its high pathogenicity and transmission due to thepresence of polybasic cleavage sites. No specific drug is available for the treatment. To identifythe potential inhibitors, we have performed molecular docking against the SARS-CoV-2 mainprotease (6Y84) with fifteen important natural xanthone compounds. The docking results showedall the compounds exhibited good binding energies and interactions with the main protease. Thevalidation of representative docking complexes through molecular dynamics simulations showedthat xanthones binds with a higher binding affinity and lower free energy than the standardligand with Brasixanthone C and Brasixanthone B on 50 ns. Natural xanthone compounds havealso passed the Absorption, Distribution, Metabolism, and Excretion (ADME) property criteriaas well as Lipinski’s rule of five. The present integrated molecular docking and dynamicssimulations study unveil the use of xanthones as potential antiviral agents against SARS-CoV-2.

7.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323104

ABSTRACT

Background: With the start of the Coronavirus disease19 (COVID19) pandemic, the Coronavirus has mutated constantly. Recently a new variant called Delta plus has been reported in few countries, including South Africa, Brazil and India. The Delta plus variant contains an additional mutation called K417N on the coronavirus spike. The present study aims to determine the virulence and transmissibility of the Delta plus variant and to check the efficiency of different antibodies on its neutralization. Materials: and Methods Different computational tools such as PROVEAN, an online tool, HOPE server, simulation using CABS Flex, Clus pro, an online docking tool, were used to predict the structure and function of Delta plus variant by performing a comparative study with wild type protein. Also, to find an effective antibody against Delta plus variant, antigen-antibody docking studies were conducted through Clus pro server. Furthermore, we performed a 2D interaction diagram analysis to find the amino acid residue's interaction against antibodies. Results: PROVEAN and HOPE showed the mutation (K417N) in the S-glycoprotein of Delta plus as NEUTRAL mutation. This mutation causes the loss of cysteine bonds leading to the destabilization of the 3D structure of spike protein. Furthermore, the RMSF plot emphasizing the 17 th amino acid position of wild and Delta plus mutant revealed the high fluctuation of mutant protein structure compared to the wild protein structure. Further, a comparative docking study against hACE2 shows higher binding energy of wild-type RBD (-751.7 kcal/mol) than mutant RBD (-750.1 kcal/mol). Moreover, antigen-antibody docking study revealed higher affinity of BD-23 Fab antibodies with greater interaction energy ( -997 kcal/mol) compared to other antibodies and thus may prove to be a promising therapeutic against Delta plus variant. Conclusion: Delta plus variant is less stable, has a lower binding affinity to hACE2 and has less virulence than wild type. However, the BD-23 Fab antibody has shown a more significant association for this variant and can be used in its treatment.

8.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323103

ABSTRACT

Background: A global outbreak of coronavirus disease 19 (COVID-19) led researchers to investigate various active compounds that can inhibit the replication of SARS-CoV2 (severe acute respiratory syndrome coronavirus 2). The present work targets to evaluate small covalent synthetic molecules through a virtual screening and docking approach that can efficiently inhibit Spike Glycoprotein of SARS CoV2. Methods: We retrieved around 50,000 small covalent synthetic molecules through the American chemical society (CAS) database. The initial evaluation of these synthetic molecules depends on the ADMET screening. A Lipinski's Rule of Five (RO5) was also applied to find whether the drug met the criteria of good bioavailability. Then, the further selection was made through virtual screening using BIOVIA Discovery Studio. Further, comparison among top hits was performed via a docking approach based on the binding energy (kcal/mol) calculated using the AutoDock Vina plugin and Patch Dock-like docking engines. Finally, the selected top five molecules were compared for their binding efficiency with reference drugs like Favipiravir, Chloroquine, Ribavirin, Hydroxychloroquine (approved by the FDA), and molecules with better binding affinity than reference drugs was selected. Results: In the first tier of selection, 215 molecules were screened out, satisfying all the necessary conditions of RO5 and ADMET. Among 215 molecules screened, only 203 molecules were stable in structure to undergo the second tier of target-based virtual screening. Further, based upon the LibDock score generated by virtual screening, the top five molecules with the highest LibD score were selected. Molecular docking of these five selected compounds reveals compound2 (3-ethyl-5-propyladamantan-1-amine) with the best binding energy. Furthermore, we compared the binding affinity of 3-ethyl-5-propyladamantan-1-amine with reported drugs that show 3-ethyl-5-propyladamantan-1-amine as the most promising ligand efficient hydrogen bond interactions with amino acid residues of protein which provides more excellent stability in the docked region of the protein with efficient binding energy as compared to the reference molecule. Moreover, Compound2 also has a high oral bioavailability, non-mutagenicity, non-toxicity and follows all RO5 criteria. Conclusion: Thus, it has potential as an antiviral covalent synthetic molecule that may prevent the replication of spike protein. These findings are just preliminary selection to facilitate the upcoming tests from in vivo and in vitro studies.

9.
Frontiers in immunology ; 12, 2021.
Article in English | EuropePMC | ID: covidwho-1651316

ABSTRACT

Innate immunity is the frontline of defense against infections and tissue damage. It is a fast and semi-specific response involving a myriad of processes essential for protecting the organism. These reactions promote the clearance of danger by activating, among others, an inflammatory response, the complement cascade and by recruiting the adaptive immunity. Any disequilibrium in this functional balance can lead to either inflammation-mediated tissue damage or defense inefficiency. A dynamic and coordinated gene expression program lies at the heart of the innate immune response. This expression program varies depending on the cell-type and the specific danger signal encountered by the cell and involves multiple layers of regulation. While these are achieved mainly via transcriptional control of gene expression, numerous post-transcriptional regulatory pathways involving RNA-binding proteins (RBPs) and other effectors play a critical role in its fine-tuning. Alternative splicing, translational control and mRNA stability have been shown to be tightly regulated during the innate immune response and participate in modulating gene expression in a global or gene specific manner. More recently, microRNAs assisting RBPs and post-transcriptional modification of RNA bases are also emerging as essential players of the innate immune process. In this review, we highlight the numerous roles played by specific RNA-binding effectors in mediating post-transcriptional control of gene expression to shape innate immunity.

10.
Mol Ther ; 30(5): 2058-2077, 2022 05 04.
Article in English | MEDLINE | ID: covidwho-1612108

ABSTRACT

The ongoing COVID-19 pandemic highlights the need to tackle viral variants, expand the number of antigens, and assess diverse delivery systems for vaccines against emerging viruses. In the present study, a DNA vaccine candidate was generated by combining in tandem envelope protein domain III (EDIII) of dengue virus serotypes 1-4 and a dengue virus (DENV)-2 non-structural protein 1 (NS1) protein-coding region. Each domain was designed as a serotype-specific consensus coding sequence derived from different genotypes based on the whole genome sequencing of clinical isolates in India and complemented with data from Africa. This sequence was further optimized for protein expression. In silico structural analysis of the EDIII consensus sequence revealed that epitopes are structurally conserved and immunogenic. The vaccination of mice with this construct induced pan-serotype neutralizing antibodies and antigen-specific T cell responses. Assaying intracellular interferon (IFN)-γ staining, immunoglobulin IgG2(a/c)/IgG1 ratios, and immune gene profiling suggests a strong Th1-dominant immune response. Finally, the passive transfer of immune sera protected AG129 mice challenged with a virulent, non-mouse-adapted DENV-2 strain. Our findings collectively suggest an alternative strategy for dengue vaccine design by offering a novel vaccine candidate with a possible broad-spectrum protection and a successful clinical translation either as a stand alone or in a mix and match strategy.


Subject(s)
COVID-19 , Dengue Vaccines , Dengue Virus , Dengue , Vaccines, DNA , Antibodies, Neutralizing , Antibodies, Viral , Dengue/prevention & control , Dengue Vaccines/genetics , Dengue Virus/genetics , Humans , Pandemics , Viral Envelope Proteins/genetics
11.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-295905

ABSTRACT

Following the recent clinical clearance of an Indian DNA COVID-19 vaccine, India and Africa are potential regions where DNA vaccines may become a major delivery system subject to a range of immunological and regulatory scrutiny. The ongoing COVID pandemic highlights the need to tackle viral variants and expand the number of antigens and assess diverse delivery systems. To address some of these key issues, we have created a Dengue DNA vaccine candidate with the EDIII region as the key antigen given the promise of this segment in not causing ADE, a challenge with this disease. In addition, we have added the NS1 region to broaden the immune response. Following a large Dengue viral sequencing exercise in India, complemented with data from east Africa, our approach was to generate a consensus of four serotypes ED3-NS1 vaccine to explore tackling the issue of diversity. Our In silico structural analysis of EDIII consensus vaccine sequence revealed that epitopes are structurally conserved and immunogenic across HLA diversity. Vaccination of mice with this construct induced pan-serotype neutralizing antibodies and antigen-specific T cell responses. Furthermore, the DNA vaccination confers protection against DENV challenge in AG129 mice. Finally, assaying of intracellular staining for IFN-γ, immunoglobulin IgG2(a/c) /IgG1 ratios as well as immune gene profiling suggested a strong Th1-dominant immune response. Our Dengue DNA platform with a focus on Indo-African sequences offers an approach for assessing cross reactive immunity in animal models and lays the foundation for human vaccine roll out either as a stand-alone or mix and match strategy.

12.
Clin Epidemiol Glob Health ; 12: 100902, 2021.
Article in English | MEDLINE | ID: covidwho-1527608

ABSTRACT

INTRODUCTION: COVID-19 and subsequent country-wide lockdown has impacted smokeless tobacco (SLT) product availability in India. We aimed to examine SLT quitting during COVID-19 lockdown among SLT users who consented to be enrolled in a cessation programme. METHODS: Between January-March 2020, we screened 227 exclusive SLT users to be enrolled in a randomized-controlled feasibility study on SLT cessation. However, all activities were suspended due to national lockdown in response to the COVID-19 pandemic. To examine the quitting intention and behaviour during COVID-19 lockdown, we re-contacted these individuals telephonically; during September-October 2020. RESULTS: Of 227 participants, 87 (38.3%) could not be contacted on phone. We conducted telephonic qualitative interviews and assessed the SLT use status, willingness to quit and participate in the SLT cessation trial among the remaining 140 participants. Among these, 12.1% (17/140) showed no willingness to participate in the study due to migration. Since COVID-19 lockdown, 32.1% (45/140) participants reported quitting SLT due to non-availability, increased cost of products, shifts in community norms and family pressures. CONCLUSIONS: COVID-19 pandemic presented an opportunity for tobacco cessation as stringent bans and isolation from social circles enabled tobacco cessation. It also triggered improvement in dissemination of public health information at an unprecedented scale, particularly related to the vulnerability of tobacco users to co-morbidities and harm from SARS CoV-2 infection. Implementation of strict bans on sale and consumption of SLT and strengthening of cessation support may lead to sustainable tobacco control. This study provides insight into effective policy strategies to reduce SLT use; which need to be substantiated with adequate cessation support.

13.
Sustainability ; 13(21):11855, 2021.
Article in English | MDPI | ID: covidwho-1488721

ABSTRACT

The progress of Indoor Environmental Quality (IEQ) research in school buildings has increased profusely in the last two decades and the interest in this area is still growing worldwide. IEQ in classrooms impacts the comfort, health, and productivity of students as well as teachers. This article systematically discusses IEQ parameters related to studies conducted in Indian school classrooms during the last fifteen years. Real-time research studies conducted on Indoor Air Quality (IAQ), Thermal Comfort (TC), Acoustic Comfort (AcC), and Visual Comfort (VC) in Indian school classrooms from July 2006 to March 2021 are considered to gain insight into the existing research methodologies. This review article indicates that IEQ parameter studies in Indian school buildings are tortuous, strewn, inadequate, and unorganized. There is no literature review available on studies conducted on IEQ parameters in Indian school classrooms. The results infer that in India, there is no well-established method to assess the indoor environmental condition of classrooms in school buildings to date. Indian school classrooms are bleak and in dire need of energy-efficient modifications that maintain good IEQ for better teaching and learning outcomes. The prevailing COVID-19 Pandemic, Artificial Intelligence (AI), National Education Policy (NEP), Sick Building Syndrome (SBS), Internet of Things (IoT), and Green Schools (GS) are also discussed to effectively link existing conditions with the future of IEQ research in Indian school classrooms.

14.
Front Chem ; 9: 744376, 2021.
Article in English | MEDLINE | ID: covidwho-1485033

ABSTRACT

The ongoing COVID-19 pandemic, caused by SARS-CoV-2, has now spread across the nations with high mortality rates and multifaceted impact on human life. The proper treatment methods to overcome this contagious disease are still limited. The main protease enzyme (Mpro, also called 3CLpro) is essential for viral replication and has been considered as one of the potent drug targets for treating COVID-19. In this study, virtual screening was performed to find out the molecular interactions between 36 natural compounds derived from sesame and the Mpro of COVID-19. Four natural metabolites, namely, sesamin, sesaminol, sesamolin, and sesamolinol have been ranked as the top interacting molecules to Mpro based on the affinity of molecular docking. Moreover, stability of these four sesame-specific natural compounds has also been evaluated using molecular dynamics (MD) simulations for 200 nanoseconds. The molecular dynamics simulations and free energy calculations revealed that these compounds have stable and favorable energies, causing strong binding with Mpro. These screened natural metabolites also meet the essential conditions for drug likeness such as absorption, distribution, metabolism, and excretion (ADME) properties as well as Lipinski's rule of five. Our finding suggests that these screened natural compounds may be evolved as promising therapeutics against COVID-19.

15.
Mater Today Proc ; 56: 3211-3215, 2022.
Article in English | MEDLINE | ID: covidwho-1440255

ABSTRACT

During the Disease outbreak and in the future, there will be a lot of learning. Since the pandemic has interrupted global schooling, remote learning has emerged as a viable option, depending on machine learning to accomplish its goals. Using the example of ten international science journals that speak out about artificial intelligence in education today and the future of earning, we hope to gain a better understanding of the large extend of the power of artificial intelligence in education, both during the COVID-19 period and during the future learning time frame. Additionally, in addition to evaluating 10 articles, we used an internet search engine to look for relevant material. We conducted searches using terms such as artificial intelligence, learning during a pandemic, and Machine learning, among other things. After that, we used a phenomenological technique to confirm that our results answered the research questions, which was done in accordance with a qualitative approach. Our findings can be summarized by taking into account the evidence from research and literature. Among our findings are that the detailed assessment of artificial intelligence in education, the use of AI in education, typical learning in the pandemic era, and the role of artificial intelligence (AI) disease outbreak learning are all important for both current and future residents. While statistical methods and automated based on learning jobs that are smarter than normal continue to be important, learning is becoming more automated. It helps individuals to be more concentrated on their learning opportunities and to recognize when they do not grasp a subject completely. First and foremost, the instructors provide valuable assistance throughout the assessment process of student learning outcomes.

16.
J Med Phys ; 46(3): 189-196, 2021.
Article in English | MEDLINE | ID: covidwho-1413027

ABSTRACT

PURPOSE: The purpose of this study is to analyze the utility of Convolutional Neural Network (CNN) in medical image analysis. In this study, deep learning (DL) models were used to classify the X-ray into COVID, viral pneumonia, and normal categories. MATERIALS AND METHODS: In this study, we have compared the results 9 layers CNN model (9 LC) developed by us with 2 transfer learning models (Visual Geometry Group) 16 and VGG19. Two different datasets used in this study were obtained from the Kaggle database and the Radiodiagnosis department of our institution. RESULTS: In our study, VGG16 yields the highest accuracy among all three models for different datasets as the Kaggle dataset-94.96% and the department of Radiodiagnosis dataset 85.71%. Although, the precision was found better while using 9 LC and VGG19 for both datasets. CONCLUSIONS: DL can help the radiologists in the speedy prediction of diseases and detecting minor features of the disease which may be missed by the human eye. In the present study, we have used three models, i.e.,, CNN with 9 LCs, VGG16, and VGG19 transfer learning models for the classification of X-ray images with good accuracy and precision. DL may play a key role in analyzing the medical image dataset.

17.
Academy of Strategic Management Journal ; 20:1-6, 2021.
Article in English | ProQuest Central | ID: covidwho-1391063

ABSTRACT

The strategic human resource management approach can help HR managers in applying emotional intelligence. In this research paper, the authors are looking for an effective solution for human resource managers in the form of strategic human resource management to manage the crisis at the organizational level. The emotional intelligence of the human resource managers will also play an important role in managing the employees. The strategic human resource management system can provide a sustainable competitive advantage to the employees, and it can further help them in improving their competencies and capabilities.

18.
Academy of Marketing Studies Journal ; 25(3):1-13, 2021.
Article in English | ProQuest Central | ID: covidwho-1268990

ABSTRACT

The purpose of this study is to discuss the importance of technology for SMEs. The world is moving towards technology 5.0, SMEs have not able to adopt technology 2.0 effectively. COVID-19 pandemic has taught the world about the importance of technology in effective working from remote places. In the first section of this study, the authors will discuss the importance of technology adoption;later, the second section will focus on the various challenges in the adoption of technology. The research methodology is based on a systematic literature review. The authors have reviewed the literature of the last twenty years to judge the challenges pertaining to technology adoption. The literature has been reviewed in a longitudinal manner. The findings of this study suggest that the significant challenges in technology adoption are the cost of technology and infrastructure, technical skills and efficiency, adoption challenges, lack of organizational support, and governmental support.

19.
Netw Model Anal Health Inform Bioinform ; 10(1): 44, 2021.
Article in English | MEDLINE | ID: covidwho-1265590

ABSTRACT

Coronavirus disease 2019 (COVID-19) is caused by a Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2), which is a positive-strand RNA virus. The SARS-CoV-2 genome and its association to SAR-CoV-1 vary from ca. 66 to 96% depending on the type of betacoronavirideae family members. With several drugs, viz. chloroquine, hydroxychloroquine, ivermectin, artemisinin, remdesivir, azithromycin considered for clinical trials, there has been an inherent need to find distinctive antiviral mechanisms of these drugs. Curcumin, a natural bioactive molecule has been shown to have therapeutic potential for various diseases, and its effect on COVID-19 is also currently being explored. In this study, we show the binding potential of curcumin targeted to a variety of SARS-CoV-2 proteins, viz. spike glycoproteins (PDB ID: 6VYB), nucleocapsid phosphoprotein (PDB ID: 6VYO), spike protein-ACE2 (PDB ID: 6M17) along with nsp10 (PDB ID: 6W4H) and RNA dependent RNA polymerase (PDB ID: 6M71) structures. Furthermore, representative docking complexes were validated using molecular dynamics simulations and mechanistic studies at 100 ns was carried on nucleocapsid and nsp10 proteins with curcumin complexes which resulted in stable and efficient binding energies and correlated with that of docked binding energies of the complexes. Both the docking and simulation studies indicate that curcumin has the potential as an antiviral against COVID-19.

20.
Pharmacol Rep ; 73(3): 926-938, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1220621

ABSTRACT

INTRODUCTION: Drug repurposing is the need of the hour considering the medical emergency caused by the COVID-19 pandemic. Recently, cytokine storm by the host immune system has been linked with high viral load, loss of lung function, acute respiratory distress syndrome (ARDS), multiple organ failure, and subsequent fatal outcome. OBJECTIVE: This study aimed to identify potential FDA approved drugs that can be repurposed for COVID-19 treatment using an in-silico analysis. METHODS: In this study, virtual screening of selected FDA approved drugs was performed by targeting the main protease (Mpro) of SARS-CoV-2 and the key molecules involved in the 'Cytokine storm' in COVID-19 patients. Based on our preliminary screening supported by extensive literature search, we selected FDA approved drugs to target the SARS-CoV-2 main protease (Mpro) and the key players of cytokine storm, TNF-α, IL-6, and IL-1ß. These compounds were examined based on systematic docking studies and further validated using a combination of molecular dynamics simulations and molecular mechanic/generalized/Born/Poisson-Boltzmann surface area (MM/G/P/BSA) free energy calculations. RESULTS: Based on the findings, Rifampicin and Letermovir appeared as the most promising drug showing a very good binding affinity with the main protease of SARS-CoV-2 and TNF-α, IL-6, and IL-1ß. However, it is pertinent to mention here that our findings need further validation by in vitro analysis and clinical trials. CONCLUSION: This study provides an insight into the drug repurposing approach in which several FDA approved drugs were examined to inhibit COVID-19 infection by targeting the main protease of SARS-COV-2 and the cytokine storm.


Subject(s)
Acetates/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Quinazolines/therapeutic use , Rifampin/therapeutic use , COVID-19/metabolism , Cytokine Release Syndrome/drug therapy , Cytokines/metabolism , Drug Repositioning/methods , Humans , Molecular Docking Simulation , SARS-CoV-2/drug effects , Viral Proteases/metabolism
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