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1.
Journal of Food Biochemistry ; : 1, 2022.
Artigo em Inglês | Academic Search Complete | ID: covidwho-1840460

RESUMO

Practical applications The current COVID‐19 pandemic is severely threatening public healthcare systems around the globe. Some supporting therapies such as remdesivir, favipiravir, and ivermectin are still under the process of a clinical trial, it is thus urgent to find alternative treatment and prevention options for SARS‐CoV‐2. In this regard, although many natural products have been tested and/or suggested for the treatment and prophylaxis of COVID‐19, carotenoids as an important class of natural products were underexplored. The dietary supplementation of some carotenoids was already suggested to be potentially effective in the treatment of COVID‐19 due to their strong antioxidant properties. In this study, we performed an in silico screening of common food‐derived carotenoids against druggable target proteins of SARS‐CoV‐2 including main protease, helicase, replication complex, spike protein and its mutants for the recent variants of concern, and ADP‐ribose phosphatase. Molecular docking results revealed that some of the carotenoids had low binding energies toward multiple receptors. Particularly, crocin had the strongest binding affinity (−10.5 kcal/mol) toward the replication complex of SARS‐CoV‐2 and indeed possessed quite low binding energy scores for other targets as well. The stability of crocin in the corresponding receptors was confirmed by molecular dynamics simulations. Our study, therefore, suggests that carotenoids, especially crocin, can be considered an effective alternative therapeutics and a dietary supplement candidate for the prophylaxis and treatment of SARS‐CoV‐2.In this study, food‐derived carotenoids as dietary supplements have the potential to be used for the prophylaxis and/or treatment of SARS‐CoV‐2. Using in silico techniques, we aimed at discovering food‐derived carotenoids with inhibitory effects against multiple druggable sites of SARS‐CoV‐2. Molecular docking experiments against main protease, helicase, replication complex, spike protein and its mutants for the recent variants of concern, and ADP‐ribose phosphatase resulted in a few carotenoids with multitarget inhibitory effects. Particularly, crocin as one of the main components of saffron exhibited strong binding affinities to the multiple drug targets including main protease, helicase, replication complex, mutant spike protein of lineage B.1.351, and ADP‐ribose phosphatase. The stability of the crocin complexed with these drug targets was further confirmed through molecular dynamics simulations. Overall, our study provides the preliminary data for the potential use of food‐derived carotenoids, particularly crocin, as dietary supplements in the prevention and treatment of COVID‐19. [ FROM AUTHOR] Copyright of Journal of Food Biochemistry is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

2.
Journal of Biomolecular Structure and Dynamics ; 2022.
Artigo em Inglês | Scopus | ID: covidwho-1839741

RESUMO

The present pandemic disease COVID-19 demands an urgent need for more efficient antiviral drugs against SARS-CoV-2. Computational drug designing and discovery enable us to explore ethnomedicinal plants as a source of various lead molecules that can be used against present and future pathogens. Adiantum latifolium Lam., a common fern, is resistant to pathogens mainly due to the presence of various phytochemicals having antimicrobial properties. In our previous study, 3β-acetoxy-21α-H-hop-22(29)ene, a terpenoid has been characterized from the methanol extract of leaves of A. latifolium. The manuscript evaluates the antiviral potency of the compound against SARS-CoV-2 through molecular docking method. Proteins essential for SARS-CoV-2 multiplication in host cells are the target sites. The study revealed strong binding affinity of the compound for all the ten proteins selected, including seven nonstructural proteins, two structural proteins and one receptor protein, with a binding energy of −4.67 to −8.76 kcal/mol. MDS and MMPBSA analysis of the best ranked complex further confirmed the results. The multitargeted compound can be considered as a natural lead molecule in drug designing against COVID-19, but requires wet-lab experimentation and clinical trials. Communicated by Ramaswamy H. Sarma. © 2022 Informa UK Limited, trading as Taylor & Francis Group.

3.
J Ayurveda Integr Med ; 13(1): 100343, 2022.
Artigo em Inglês | MEDLINE | ID: covidwho-1838942

RESUMO

BACKGROUND: COVID-19 is the disease caused by SARS-CoV2, it was identified in Wuhan, China, in 2019. It then extended across the globe and was termed as a pandemic in 2020. Though research work on its vaccine and drugs are carried out across the globe, it is even necessary to look over it through alternative sciences. OBJECTIVE: The objective of this study is to look over the disease through Ayurvedic perspective, analyse possible pathologies, select appropriate drugs and to study in-silico screening on these selected drugs. MATERIALS & METHODS: Available symptoms of COVID-19 were thoroughly studied and reviewed through Ayurveda classics, internet, preprints, etc. to understand the nature of the disease with the Ayurvedic perspective. The molecular Docking and Grid were generated through Pyrx Software with Autodock. The Lipinski Rule of Five data generated from Swiss ADME software and Target prediction of selected phytoconstituents were done by Swiss target prediction. RESULTS: In Ayurveda, COVID-19 can be considered as Janapadaudhwans, Va t a -Kaphaj a Sannipatik a Jwara, Aup a sargika Vyadhi, and Dhatupaka Awastha. In the molecular docking study, the binding energy and inhibition of 6 Gingesulphonic acid from Zingiber officinalis (Sunthi) is greater than hydroxychloroquine and quinine. Most of the selected phytoconstituents follow the Lipinski rule of five. Target prediction of selected phytoconstituents was done on target of SARS-CoV-2, humoral immunity, and antiviral activity. Every selected phytoconstituents works on minimum one of the targets. CONCLUSION: Thus, from the above results obtained from reviewing Ayurveda classics and after the virtual screening of selected drugs we can conclude that Nagara di Kashaya (Sunthi, Puskarmoola, Kantakari, Guduchi) may have appreciable results in combating SARS-CoV-2. Thus, Nagara di Kashayam, a classical formulation can be a trial candidate for conducting further clinical trial.

4.
J Ayurveda Integr Med ; 13(1): 100324, 2022.
Artigo em Inglês | MEDLINE | ID: covidwho-1838938

RESUMO

BACKGROUND: Siddha Medicine is a valuable therapeutic choice which is classically used for treating viral respiratory infections, this principle of medicine is proven to contain antiviral compounds. OBJECTIVE: The study is aimed to execute the In Silico computational studies of phytoconstituents of Siddha official formulation Kabasura Kudineer and novel herbal preparation - JACOM which are commonly used in treating viral fever and respiratory infectious diseases and could be affective against the ongoing pandemic novel corona virus disease SARS-CoV-2. METHOD: Cresset Flare software was used for molecular docking studies against the spike protein SARS-CoV-2 (PDB ID: 6VSB). Further, we also conducted insilico prediction studies on the pharmacokinetics (ADME) properties and the safety profile in order to identify the best drug candidates by using online pkCSM and SwissADME web servers. RESULTS: Totally 37 compounds were screened, of these 9 compounds showed high binding affinity against SARS-CoV-2 spike protein. All the phytoconstituents were free from carcinogenic and tumorigenic properties. Based on these, we proposed the new formulation called as "SNACK-V" CONCLUSION: Based on further experiments and clinical trials, these formulations could be used for effective treatment of COVID-19.

5.
Virology ; 570:18-28, 2022.
Artigo em Inglês | CAB Abstracts | ID: covidwho-1839384

RESUMO

The challenge continues globally triggered by the absence of an approved antiviral drug against COVID-19 virus infection necessitating global concerted efforts of scientists. Nature still provides a renewable source for drugs used to solve many health problems. The aim of this work is to provide new candidates from natural origin to overcome COVID-19 pandemic. A virtual screening of the natural compounds database (47,645 compounds) using structure-based pharmacophore model and molecular docking simulations reported eight hits from natural origin against SARS-CoV-2 main proteinase (Mpro) enzyme. The successful candidates were of terpenoidal nature including taxusabietane, Isoadenolin A & C, Xerophilusin B, Excisanin H, Macrocalin B and ponicidin, phytoconstituents isolated from family Lamiaceae and sharing a common ent-kaurane nucleus, were found to be the most successful candidates. This study suggested that the diterpene nucleus has a clear positive contribution which can represent a new opportunity in the development of SARS-CoV-2 main protease inhibitors.

6.
Journal of Molecular Structure ; 1261:N.PAG-N.PAG, 2022.
Artigo em Inglês | Academic Search Complete | ID: covidwho-1839169

RESUMO

• Novel phthalimide derivatives 8 (a - f) and 9 (a-f) bearing a 1,2,3-triazole subunit were synthesized via CuAAC reactions. • Spectroscopic characterization was performed with 1H, 13C NMR, HR-MS, and FT-IR analyses. • The interactions with the proteins of SARS-CoV-2 (Mpro and PLpro) and the PPI between ACE2-S1 of the target compounds were examined via molecular docking studies. • 8a for Mpro, 8b for PLpro, and 9a for 'ACE2-S1' showed the best binding energy and predicted Ki values. • The ligand-protein stabilities were investigated via molecular dynamics simulation studies. • In silico ADMET studies were carried out. The target compounds have acceptable pharmacokinetic profiles and display low toxicity levels. • Finally, the target compounds may prevent the entry of SARS-CoV-2 into the host-cell, and the progression of the Mpro and PLpro proteins. In the present study, novel phthalimide derivatives 8 (a - f) and 9 (a-f) bearing a 1,2,3-triazole subunit were synthesized via CuAAC reactions and characterized by 1H, 13C NMR, HR-MS, and FT-IR analyses. To support the fight against SARS-CoV-2, in silico molecular docking studies were carried out to examine their interactions with the proteins of SARS-CoV-2 (Mpro and PLpro) and the protein-protein interactions (PPI) between the ACE2-spike (S1) in comparison with various inhibitors reported to be active by in vitro experiments. The ligand-protein stabilities of compounds 8a -Mpro, 8b -PLpro, and 9a -'ACE2-S1' showing the best binding energy and predicted inhibition constant values (Ki) were examined by molecular dynamics simulation studies. Finally, in silico ADMET properties of the target compounds were investigated using the Swiss ADME and ProTox-II web tools. According to in silico results, all phthalimide analogs may block the PPI between S1 and ACE2. The compounds may also inhibit the progression of the Mpro, and PLpro proteins of SARS-CoV-2. Additionally, it has been estimated that the compounds are suitable for oral administration and exhibit low levels of toxicity. [Display omitted] [ FROM AUTHOR] Copyright of Journal of Molecular Structure is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

7.
Journal of Molecular Structure ; 1261:N.PAG-N.PAG, 2022.
Artigo em Inglês | Academic Search Complete | ID: covidwho-1839168

RESUMO

• Design and synthesis of a series of hetero-cycle substituted benzimidazoles. • Straightforward and green-synthetic route. • SARS-CoV-2 screening activities against main protease and non-structural proteins. • X-ray structure of the thiophene-substituted benzimidazole. The manuscript deals with cost-effective synthesis, structural characterization and in silico SARS-CoV-2 screening activity of 5-membered heterocycle-substituted benzimidazole derivatives, 1-((1H-pyrrol-2-yl)methyl)-2-(1H-pyrrol-2-yl)-1H-benzo[d]imidazole (L1), 2-(furan-2-yl)-1-(furan-2-ylmethyl)-1H-benzo[d]imidazole (L2), 2-(thiophen-2-yl)-1-(thiophen-2-ylmethyl)-1H-benzo[d]imidazole (L3). The benzimidazole compounds were synthesized through a green-synthetic approach by coupling of 5-membered heterocyclic-carboxaldehyde and o-phenylenediamine in water under an aerobic condition. The compounds were characterized by various spectroscopic methods and X-ray structural analysis. The suitable single-crystals of the methyl derivative of L3 were grown as L3′ which crystallized in a monoclinic system and the thiophene groups co-existed in a nearly a perpendicular orientation. Further, in silico anti-SARS-CoV-2 proficiency of the synthetic derivatives is evaluated against main protease (Mpro) and non-structural proteins (nsp2 and nsp7) of SARS-CoV-2. Molecular docking and molecular dynamics analysis of the ligands (L1-L3) against Mpro and nsp2 and nsp7 for 50 ns reveal that L3 turns out to be the superlative antiviral candidate against Mpro, nsp2 and nsp7 of SARS-CoV-2 as evident from the binding score and stability of the ligand-docked complexes with considerable binding energy changes. [Display omitted] [ FROM AUTHOR] Copyright of Journal of Molecular Structure is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

8.
Computers in Biology and Medicine ; 145, 2022.
Artigo em Inglês | ProQuest Central | ID: covidwho-1838690

RESUMO

The causative agent of the COVID-19 pandemic, the SARS-CoV-2 virus has yielded multiple relevant mutations, many of which have branched into major variants. The Omicron variant has a huge similarity with the original viral strain (first COVID-19 strain from Wuhan). Among different genes, the highly variable orf8 gene is responsible for crucial host interactions and has undergone multiple mutations and indels. The sequence of the orf8 gene of the Omicron variant is, however, identical with the gene sequence of the wild type. orf8 modulates the host immunity making it easier for the virus to conceal itself and remain undetected. Variants seem to be deleting this gene without affecting the viral replication. While analyzing, we came across the conserved orf7a gene in the viral genome which exhibits a partial sequence homology as well as functional similarity with the SARS-CoV-2 orf8. Hence, we have proposed here in our hypothesis that, orf7a might be an alternative reserve of orf8 present in the virus which was compensating for the lost gene. A computational approach was adopted where we screened various miRNAs targeted against the orf8 gene. These miRNAs were then docked onto the orf8 mRNA sequences. The same set of miRNAs was then used to check for their binding affinity with the orf7a reference mRNA. Results showed that miRNAs targeting the orf8 had favorable shape complementarity and successfully docked with the orf7a gene as well. These findings provide a basis for developing new therapeutic approaches where both orf8 and orf7a can be targeted simultaneously.

9.
In Silico Pharmacol ; 10(1):5, 2022.
Artigo em Inglês | ProQuest Central | ID: covidwho-1838440

RESUMO

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global threat. Despite the production of various vaccines and different treatments, finding natural compounds to control COVID-19 is still a challenging task. Isoquinoline alkaloids are naturally occurring compounds known to have some potential antiviral activity. In this study, ten abundant isoquinoline alkaloids with antiviral activity were selected to analyze the preventive effect on COVID-19. A scrutinized evaluation based on Lipinski's rule showed that one out of ten compounds was toxic. Based on molecular docking analysis using Autodock software one of the best molecules with maximum negative binding energy was selected for further analysis. The Gromacs simulation analysis revealed that Coptisine has more action against active site M(pro) of COVID-19. Overall, to make a rational design of various preventive analogues that inhibit the COVID-19, associated in vitro and in vivo analyses are needed to confirm this claim.

10.
Structural Chemistry ; : 1-21, 2022.
Artigo em Inglês | Academic Search Complete | ID: covidwho-1838392

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected billions and has killed millions to date. Studies are being carried out to find therapeutic molecules that can potentially inhibit the replication of SARS-CoV-2. 3-chymotrypsin-like protease (3CL pro) involved in the polyprotein cleavage process is believed to be the key target for viral replication, and hence is an attractive target for the discovery of antiviral molecules. In the present study, we aimed to identify natural phytocompounds from Bridelia retusa as potential inhibitors of SARS-CoV-2 3CL pro (PDB ID: 6M2N) using in silico techniques. Molecular docking studies conducted with three different tools in triplicates revealed that ellagic acid (BR6) and (+)-sesamin (BR13) has better binding affinity than the co-crystal inhibitor “3WL” of 6M2N. BR6 and BR13 were found to have a high LD50 value with good bioavailability. 3WL, BR6, and BR13 bind to the same active binding site and interacted with the HIS41-CYS145 catalytic dyad including other crucial amino acids. Molecular dynamics simulation studies revealed stability of protein–ligand complexes as evidenced from root-mean-square deviations, root-mean-square fluctuations (RMSF), protein secondary structure elements, ligand-RMSF, protein–ligand contacts, ligand torsions, and ligand properties. BR6 (−22.3064 kcal/mol) and BR13 (−19.1274 kcal/mol) showed a low binding free energy value. The Bayesian statistical model revealed BR6 and BR13 as better protease inhibitors than 3WL. Moreover, BR6 and BR13 had already been reported to elicit antiviral activities. Therefore, we conclude that ellagic acid and (+)-sesamin as natural antiviral phytocompounds with inhibitory potential against SARS-CoV-2 3CL pro. [ FROM AUTHOR] Copyright of Structural Chemistry is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

11.
Journal of Molecular Modeling ; 28(6), 2022.
Artigo em Inglês | ProQuest Central | ID: covidwho-1838345

RESUMO

COVID-19 has recently grown to be pandemic all around the world. Therefore, efforts to find effective drugs for the treatment of COVID-19 are needed to improve humans’ life quality and survival. Since the main protease (Mpro) of SARS-CoV-2 plays a crucial role in viral replication and transcription, the inhibition of this enzyme could be a promising and challenging therapeutic target to fight COVID-19. The present study aims to identify alkaloid compounds as new potential inhibitors for SARS-CoV-2 Mpro by the hybrid modeling analyses. The docking-based virtual screening method assessed a collection of alkaloids extracted from over 500 medicinal plants and sponges. In order to validate the docking process, classical molecular dynamic simulations were applied on selected ligands, and the calculation of binding free energy was performed. Based on the proper interactions with the active site of the SARS-CoV-2 Mpro, low binding energy, few side effects, and the availability in the medicinal market, two indole alkaloids were found to be potential lead compounds that may serve as therapeutic options to treat COVID-19. This study paves the way for developing natural alkaloids as stronger potent antiviral agents against the SARS-CoV-2.

12.
Pakistan Journal of Zoology ; 54(1):433, 2022.
Artigo em Inglês | ProQuest Central | ID: covidwho-1837597

RESUMO

Coronavirus disease 2019 (COVID-19) is a pandemic and this disease has infected millions of people globally now. COVID-19 is caused by a novel beta coronavirus strain known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Once SARS-CoV-2 manages to enter the body, it identifies and binds to the angiotensin converting enzyme 2 (ACE2) receptors through the binding receptor of Spike Protein (S-protein). The present study aimed to investigate the phytochemicals as potential inhibitors of the binding domain of S protein so that the binding of COVID-19 with ACE2 receptors could be restrained. For this purpose, the library of 2113 phytochemicals was docked against the binding domain of the S-protein. Top ten compounds with maximum binding affinity to the active sites of target protein were further screened for ADMET properties by adopting SwissADME and ADMETsar online servers. The compounds namely Morin, Curcumin, Apigenin, Cedronolactone A and Matairesinol showed acceptable drug-like properties therefore these compounds can be proposed as effective inhibitors, disrupting the S-protein-ACE2 interaction. This study might help in the development of a natural and cost-effective drug against COVID-19. Further, in vivo and in vitro examinations are required to validate our results.

13.
J Ayurveda Integr Med ; 13(1): 100413, 2022.
Artigo em Inglês | MEDLINE | ID: covidwho-1838953

RESUMO

BACKGROUND: Outbreak of Corona Virus Disease in late 2019 (COVID-19) has become a pandemic global Public health emergency. Since there is no approved anti-viral drug or vaccine declared for the disease and investigating existing drugs against the COVID-19. OBJECTIVE: AYUSH-64 is an Ayurvedic formulation, developed and patented by Central Council of Research in Ayurvedic Sciences, India, has been in clinical use as anti-malarial, anti-inflammatory, anti-pyretic drug for few decades. Thus, the present study was undertaken to evaluate AYUSH-64 compounds available in this drug against Severe Acute Respiratory Syndrome-Corona Virus (SARS-CoV-2) Main Protease (Mpro; PDB ID: 6LU7) via in silico techniques. MATERIALS AND METHODS: Different molecular docking software's of Discovery studio and Auto Dock Vina were used for drugs from selected AYUSH-64 compounds against SARS-CoV-2. We also conducted 100 ns period of molecular dynamics simulations with Desmond and further MM/GBSA for the best complex of AYUSH-64 with Mpro of SARS-CoV-2. RESULTS: Among 36 compounds of four ingredients of AYUSH-64 screened, 35 observed to exhibits good binding energies than the published positive co-crystal compound of N3 pepetide. The best affinity and interactions of Akuammicine N-Oxide (from Alstonia scholaris) towards the Mpro with binding energy (AutoDock Vina) of -8.4 kcal/mol and Discovery studio of Libdock score of 147.92 kcal/mol. Further, molecular dynamics simulations with MM-GBSA were also performed for Mpro- Akuammicine N-Oxide docked complex to identify the stability, specific interaction between the enzyme and the ligand. Akuammicine N-Oxide is strongly formed h-bonds with crucial Mpro residues, Cys145, and His164. CONCLUSION: The results provide lead that, the presence of Mpro- Akuammicine N-Oxide with highest Mpro binding energy along with other 34 chemical compounds having similar activity as part of AYUSH-64 make it a suitable candidate for repurposing to management of COVID-19 by further validating through experimental, clinical studies.

14.
European Review for Medical & Pharmacological Sciences ; 26(8):2651-2661, 2022.
Artigo em Inglês | MEDLINE | ID: covidwho-1836394

RESUMO

OBJECTIVE: The study aims to predict the target and molecular mechanism of Xuebijing injection in the treatment of novel coronavirus-induced acute respiratory distress syndrome (ARDS), based on network pharmacology. MATERIALS AND METHODS: Chinese and English studies were searched to obtain the main active components of Xuebijing injection. ETCM, TCMSP and Targetnet online databases were adopted used to predict Xuebijing therapeutic targets. GeneCards, CTD and OMIM databases were researched used to research for the novel coronavirus Disease-2019 (COVID-19) and ARDS-related targets. Integrate analysis was carried out to obtain the targets of Xuebijing injection in the treatment of ARDS caused by novel coronavirus. STRING was adopted to analyze the interaction of common target proteins. GO and KEGG enrichment analyses were carried out using Bioconductor bioinformatics software package based on R software. Network visualization was performed with Cytoscape software. RESULTS: A total of 30 main active components in Xuebijing injection were collected in this study, which can act on 615 targets. The core components of Xuebijing injection in treating the coronavirus-induced ARDS are Ferulic acid, Ethyl ferulate, Albiflorin, Caffeic acid, Rosmarinic acid, Naringenin, Quercetin. Xuebijing injection has 56 target points for the treatment of ARDS caused by the novel coronavirus, among which AKT1, TNF, CASP3 and STAT3 are the core ones. The main molecular mechanisms of Xuebijing injection in treating the coronavirus-induced ARDs include PI3K-Akt, TNF, STAT3, NF-kappaB and apoptosis-related pathways. CONCLUSIONS: Xuebijing mainly treats ARDS caused by the novel coronavirus through anti-inflammation, anti-apoptosis, and regulation of immunity since it has the characteristics of multi-component, multi-target and multi-pathway.

15.
Embase; 2022.
Preprint em Inglês | EMBASE | ID: ppcovidwho-335151

RESUMO

Variants of coronavirus (SARS-CoV-2) have been spreading in a global pandemic. It is important to understand quick the infectivity of future new variants for effective countermeasure against them. In this research, we aimed to investigate the prediction of infectivity of SARSCoV-2 by using mathematical model with molecular simulation analysis and the evolutionary distance of spike protein gene (S gene) of SARS -CoV-2 in the phylogenetic analysis. We subjected the six variants and wild type (WT) of spike protein and Angiotensin-Converting Enzyme 2 (ACE2) of human to molecular docking simulation analyses in order to understand the binding affinity. Then the regression analysis of the coefficient from our mathematical model and the infectivity of SARS-CoV-2 were investigated for the prediction of infectivity. The evolutionary distance by S gene (spike protein) correlated to the infectivity of SARSCoV-2 variants. And the coefficient of mathematical model by using the results of molecular docking simulation correlated to the infectivity of SARS-CoV-2 variants, too. These results suggests that the provided data from the docking simulation for Receptor Binding Domain (RBD) of variant spike protein and ACE2 of human were valuable to the prediction of SARS-CoV-2 infectivity. Finally, we established the mathematical model for the prediction of infectivity in the SARS-CoV-2 variant by using the binding affinity under the molecular docking experiment and evolutionary distance by S gene.

16.
Mol Divers ; 2022.
Artigo em Inglês | PubMed | ID: covidwho-1826726

RESUMO

The coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is affecting human life in an unprecedented manner and has become a global public health emergency. Identification of novel inhibitors of viral infection/replication is the utmost priority to curtail COVID-19 progression. A pre-requisite for such inhibitors is good bioavailability, non-toxicity and serum stability. Computational studies have shown that curcumin can be a candidate inhibitor of certain SARS-CoV-2 proteins;however, poor bio-availability of curcumin limits its possible therapeutic application. To circumvent this limitation, we have used mitocurcumin (MC), a triphenyl phosphonium conjugated curcumin derivative, to study the ability to inhibit SARS-CoV-2 infection using molecular docking and molecular dynamics (MD) simulation. MC is serum stable and several fold more potent as compared to curcumin. Molecular docking studies revealed that MC can bind at active site of SARS-CoV-2 ADP Ribose Phosphatase (NSP3) and SARS-CoV-2 methyltransferase (NSP10-NSP16 complex) with a high binding energy of - 10.3 kcal/mol and - 10.4 kcal/mol, respectively. MD simulation (100 ns) studies revealed that binding of MC to NSP3 and NSP16 resulted in a stable complex. MC interacted with critical residues of NSP3 macro-domain and NSP10-NSP16 complex and occupied their active sites. NSP3 is known to suppress host immune responses whereas NSP10-NSP16 complex is known to prevent immune recognition of viral mRNA. Our study suggests that MC can potentially inhibit the activity of NSP3 and NSP10-NSP16 complex, resulting in compromised viral immune evasion mechanism, and thereby accentuate the innate immune mediated clearance of viral load.

17.
Proteins ; 90(5): 1029-1043, 2022 May.
Artigo em Inglês | MEDLINE | ID: covidwho-1826108

RESUMO

A multi-pronged approach with help in all forms possible is essential to completely overcome the Covid-19 pandemic. There is a requirement to research as many new and different types of approaches as possible to cater to the entire world population, complementing the vaccines with promising results. The need is also because SARS-CoV-2 has several unknown or variable facets which get revealed from time to time. In this work, in silico scientific findings are presented, which are indicative of the potential for the use of the LL-37 human anti-microbial peptide as a therapeutic against SARS-CoV-2. This indication is based on the high structural similarity of LL-37 to the N-terminal helix, with which the virus interacts, of the receptor for SARS-CoV-2, Angiotensin Converting Enzyme 2. Moreover, there is positive prediction of binding of LL-37 to the receptor-binding domain of SARS-CoV-2; this is the first study to have described this interaction. In silico data on the safety of LL-37 are also reported. As Vitamin D is known to upregulate the expression of LL-37, the vitamin is a candidate preventive molecule. This work provides the possible basis for an inverse correlation between Vitamin D levels in the body and the severity of or susceptibility to Covid-19, as widely reported in literature. With the scientific link put forth herein, Vitamin D could be used at an effective, medically prescribed, safe dose as a preventive. The information in this report would be valuable in bolstering the worldwide efforts to eliminate the pandemic as early as possible.


Assuntos
COVID-19 , COVID-19/tratamento farmacológico , Catelicidinas , Humanos , Pandemias , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/química , Vitamina D
18.
International Journal of Pharmacy and Pharmaceutical Sciences ; 14(4):44-50, 2022.
Artigo em Inglês | EMBASE | ID: covidwho-1822680

RESUMO

Objective: The aim of the present study was to assess bioactive compounds found in Tulsi as potential COVID-19 Mpr °inhibitor using molecular docking and to provide scientific justification in term of its active ingredient to target protein for prevention and symptomatic treatment of COVID-19. Methods: COVID-19 Mpr °was docked with eight phytochemicals of Ocimum sanctum Linn. Using Autodock 4.2. Determination of active site and visualization of molecular interactions between ligands and target enzyme was done by Biovia Discovery Studio 4.5. Results: Our result demonstrates that Vicenin, Caryophyllene, Cirsimaritin, Isothymusin and Isothymonin have a better binding affinity to target enzyme. However, only Vicenin exhibited better binding energy i.e.-7.02 kcal/mol to COVID-19 Main protease among other phytochemicals through some responsible interactions to inhibit the replication of SARS-CoV-2 in the human body, whereas Caryophyllene and Cirsimaritin exhibited similar binding affinity i.e.-6.46 kcal/mol but different interactions with target enzyme. Conclusion: Tulsi (Ocimum sanctum Linn.) is a preeminent traditional drug of Ayurveda for prophylaxis and treatment of various ailments, including respiratory disorders like cough, cold and flu. With no specific therapies available, reevaluating and repurposing traditional drugs could be an effective approach for the prevention and treatment of SARS-CoV-2 infection. Therefore our study provides scientific evidence for the potential use of Tulsi as an adjunct therapy for the prevention and symptomatic treatment of COVID-19. However, further in vitro and in vivo studies should be conducted to validate use of proposed compounds in drug discovery and as therapeutics against COVID-19.

19.
International Journal of Current Pharmaceutical Research ; 14(2):5-10, 2022.
Artigo em Inglês | EMBASE | ID: covidwho-1822678

RESUMO

Covid Virus particles engage with host cells via the ACE-2 and GRP78 receptors, transferring the genome particle to the host cell and transforming it into a replicating machine. RdRP is a key protein in the replication mechanism of all RNA viruses. 3CLpro is a cleavage enzyme that breaks down polyproteins into non-structural polyproteins. All four elements of the Covid viral particle are required for its propagation and action, and blocking any one of them can shut down the entire system. EGCG and Theaflavins are flavonoids that block virus particles from attaching to the host cell's ACE-2 and GRP78 receptors, preventing the genome from being transferred into the cell. EGCG binds to 3CLpro with a molecular docking value of 11.7, while TF3 has a docking score of 10.574, indicating that it prevents host cell contact. TF binds to RdRP with a binding energy of 9.11 kcal/mol, implying that RdRP activities are interfered with. Furthermore, these flavonoids have anti-inflammatory properties and reduce the action of cytokines, which can cause serious respiratory difficulties. Except these two there are many others flavonoids which possess anti-inflammatory and anti-viral properties. All of these data suggest that flavonoids could be a useful treatment for SARS-CoV19;however, the issue of stability and bioavailability arises because it is unstable at lungs pH.

20.
Egyptian Journal of Medical Human Genetics ; 23(1), 2022.
Artigo em Inglês | EMBASE | ID: covidwho-1822226

RESUMO

Background: As the new pandemic created by COVID-19 virus created the need of rapid acquisition of a suitable vaccine against SARS-CoV-2 to develop Immunity and to reduce the mortality, the aim of this study was to identify SARS-CoV-2 S protein and N antigenic epitopes by using immunoinformatic methods to design a vaccine against SARS-CoV-2, for which S and N protein-dependent epitopes are predicted. B cell, CTL and HTL were determined based on antigenicity, allergenicity and toxicity that were non-allergenic, non-toxic, and antigenic and were selected for the design of a multi-epitope vaccine structure. Then, in order to increase the safety of Hbd-3 and Hbd-2 as adjuvants, they were connected to the N and C terminals of the vaccine construct, respectively, with a linker. The three-dimensional structure of the structure was predicted and optimized, and its quality was evaluated. The vaccine construct was ligated to MHCI. Finally, after optimizing the codon to increase expression in E. coli K12, the vaccine construct was cloned into pET28a (+) vector. Results: Epitopes which were used in our survey were based on non-allergenic, non-toxic and antigenic. Therefore, 543-amino-acid-long multi-epitope vaccine formation was invented through linking 9 cytotoxic CTL, 5 HTL and 14 B cell epitopes with appropriate adjuvants and connectors that can control the SARS coronavirus 2 infection and could be more assessed in medical scientific researches. Conclusion: We believe that the proposed multi-epitope vaccine can effectively evoke an immune response toward SARS-CoV-2.

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