Rapid degradation of chloroquine derivatives in a novel advanced reduction process: role of intramolecular hydrogen bond in the formation of excited triplet state compound

The role of triplet excited state compounds (TESC) in contaminants degradation by advanced reduction processes (ARPs) is rarely reported. In this study, Salicylic acid derivatives (SAD, e.g. Salicylic Acid (SA) and Sulfosalicylic acid (SSA)) were applied in ultraviolet activated sulfite process (UV/Sulfite) to generate TESC and enhance the decomposition of chloroquine derivatives (CQD, antiviral drugs being used for treating COVID-19 infection, e.g. chloroquine phosphate (CP)). The results indicated that the pseudo 1st order rate constant of CP (kobs-CP) increased by 2.76 and 6.26 fold, which increased from 9.10 × 10–4 s–1 in UV/Sulfite process to 2.51 × 10–3 s–1, 5.72 × 10–3 s–1 in UV/Sulfite/SA and UV/Sulfite/SSA process respectively. Similar phenomena were observed in other CQDs. Transient absorption spectra demonstrated that both triplet excited state SAD (3SAD*) and hydrated electron (eaq–) were the reactive intermediates in UV/Sulfite/SAD process, and contribute to the abatement of CP. The enhancement of SAD on contaminants degradation in UV/Sulfite/SAD process could attribute to the strong acceleration of eaq– toward the formation of 3SAD* in its photosensitive process, where SAD with intramoleuclar hydrogen bond would not undergo a directly photoionization process after absorbing a photon but undergo intersystem crossing to transform into 3SAD* which was then ionized to eaq– by biphotonic process, and constitute a hydrated electrons mediated photosensitization cycle with the supplement of eaq– from UV/Sulfite process. The higher CP degradation rate in UV/Sulfite/SSA process than that in UV/Sulfite/SA process was ascribed to a higher second order rate constant of 3SSA* toward CP and a higher yield of 3SSA*, which resulted from its higher intramolecular hydrogen bond energy enhancing photosensitization and photoionization.

Towards a free energy-based elastic network model and its application to the SARS-COV2 binding to ACE2.

Classical normal mode analysis (cNMA) is a standard method for studying the equilibrium vibrations of macromolecules. A major limitation of cNMA is that it requires a cumbersome step of energy minimization that also alters the input structure significantly. Variants of normal mode analysis (NMA) exist that perform NMA directly on PDB structures without energy minimization, while maintaining most of the accuracy of cNMA. Spring-based NMA (sbNMA) is such a model. sbNMA uses an all-atom force field as cNMA does, which includes bonded terms such as bond stretching, bond angle bending, torsional, improper, and non-bonded terms such as van der Waals interactions. Electrostatics was not included in sbNMA because it introduced negative spring constants. In this work, we present a way to incorporate most of the electrostatic contributions in normal mode computations, which marks another significant step toward a free-energy-based elastic network model (ENM) for NMA. The vast majority of ENMs are entropy models. One significance of having a free energy-based model for NMA is that it allows one to study the contributions of both entropy and enthalpy. As an application, we apply this model to study the binding stability between SARS-COV2 and angiotensin converting enzyme 2 (or ACE2). Our results show that the stability at the binding interface is contributed nearly equally by hydrophobic interactions and hydrogen bonds.

Curcumin from Curcuma longa L. as Dual Inhibitors Against Indonesian SARS-CoV-2 Isolates: A Molecular Docking Study

COVID-19 has become a global pandemic since 2020. The search for promising drugs based on the abundant herbal ingredients in Indonesia is one of the breakthroughs. Curcumin is a chemical compound with various potentials such as antioxidant, anti-inflammatory and antiviral. We conducted a molecular docking analysis to determine the potential of curcumin against SARS-CoV-2 non-structural and structural proteins, such as the main protease and spike protein. This study used the compound of curcumin (PubChem CID: 969516) from Curcuma longa L. or turmeric and two Indonesian SARS-CoV-2 isolates that have been deposited in the GISAID database (hCoV-19/Indonesia/JI-PNF-217315/2021 - EPI_ ISL_12777089 or lineage B.1.617.2 and hCoV-19/Indonesia/JI-PNF-211373/2021 - EPI_ISL_6425649 or lineage B.1.470). In addition, we used molnupiravir (PubChem CID: 145996610) as a drug control. We performed molecular docking analysis with PyRx software 0.9.9 (academic license) and visualization of molecular docking results with PyMOL software 2.5.4 (academic license). The results of this study found that curcumin had good potential against main protease and spike protein compared to the drug (control). In summary, we suggested that curcumin is a potential drug candidate against SARS-CoV-2. However, there is a need for future wet laboratory-based pre-clinical research such as in vitro and in vivo.Copyright © 2023 Phcogj.Com.

Molecular Docking and Dynamics of Phytochemicals From Chinese Herbs With SARS-CoV-2 RdRp

The novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is causing coronavirus disease 2019 (COVID-19) pandemic. Ancient Chinese herbal formulas are effective for diseases caused by viral infection, and their effects on COVID-19 are currently being examined. To directly evaluate the role of Chinese herbs in inhibiting replication of SARS-CoV-2, we investigated how the phytochemicals from Chinese herbs interact with the viral RNA-dependent RNA polymerase (RdRP). Total 1025 compounds were screened, and then 181compounds were selected for molecular docking analysis. Four phytochemicals licorice glycoside E, diisooctyl phthalate, (-)-medicocarpin, and glycyroside showed good binding affinity with RdRp. The best complex licorice glycoside E/RdRp forms 3 hydrogen bonds, 4 hydrophobic interactions, 1 pair of Pi-cation/stacking, and 4 salt bridges. Furthermore, docking complexes licorice glycoside E/RdRp and diisooctyl phthalate/RdRp were optimized by molecular dynamics simulation to obtain the stable conformation. These studies indicate that they are promising as antivirals against SARS-CoV-2.Copyright © The Author(s) 2022.

In Silico Analysis of Bioactive Compounds from Sea Urchin (Echinometra mathaei) against SARS-COV-2

SARS-CoV-2 is a kind of coronavirus that produces Covid-19 illness, which is still a public health concern in Indonesia. Meanwhile, an effective drug has not yet been found and although vaccination has been carried out, in several regions and neighboring countries there is still an increase in Covid-19 cases. This study aimed to obtain bioactive compounds from sea urchins (Echinometra mathaei) that have greater antiviral potential and lower toxicity than remdesivir. This research was started by predicting druglikeness with SwissADME, followed ADMET predicition with pkCSM online, and docking of molecule using the Molegro Virtual Docker (MVD) 5.5 software against the main protease (Mpro) target (PDB ID: 6W63). The results showed that six compounds from sea urchins (Echinometra mathaei) had antiviral activity, where the bioactive compound from sea urchins (Echinometra mathaei) with the highest affinity was shown by Spinochrome C a smaller rerank score compared with Remdesivir and native ligand (X77). So that Spinochrome C compounds are candidates as SARS-CoV-2 inhibitors potential developed drug.Copyright Published by Oriental Scientific Publishing Company © 2023.

A new short synthesis route for favipiravir and its analogue: Their tautomerization behaviour

The study of tautomerism in biologically relevant heterocycles is essential, as it directly affects their chemical properties and biological function. Lactam-lactim tautomerization in pyridine/pyrazine derivatives is such a phenomenon. Favipiravir, a pyrazine derivative, is an essential antiviral drug molecule having notable performance against SARS-CoV-2. Along with a better yielding synthetic method for favipiravir, we have also investigated the lactam-lactim tautomerization of favipiravir and its analogous molecules. Most of these molecules were crystalized and studied for various interactions in their lattice. Many interesting supramolecular interactions such as hydrogen bonding, pi-pi stacking and halogen bonding were revealed during the analysis. Some of these structures show interesting F-F halogen bonding and water channels in their solid state.Copyright © 2022 The Royal Society of Chemistry.

Valorization of biomass ash for the effective removal of dipyrone from water: an efficient and low-cost option

Background: In order to propose a destination for the bottom ash generated from biomass burning, its morphology, functional groups and mineral phases were studied. Dipyrone has been extensively used as an antipyretic, increased due to cases of COVID-19, and due to excretion by urine, incorrect disposal and industrial effluents has been destined to wastewater, being harmful to human and animal life. The present study proposes using biomass ash for the adsorption of dipyrone. Result(s): The characterization of biomass ash shows a sufficient surface area size for adsorption, and a mainly amorphous structure with some peaks of quartz, calcite and other mineral phases. The results show that the kinetic model which best describes the adsorption is the pseudo-first-order model. The Langmuir model best fits at 25 degreeC, and the Freundlich model best describes the adsorption at 35 and 45 degreeC. The thermodynamic parameters indicated that the process is endothermic with a maximum adsorptive capacity of 65.27 mg g-1. In addition, the adsorption is spontaneous, disordered and chemical. The ionic strength study reveals that the adsorbent is promising for real effluent treatment and there is evidence that electrostatic interaction is not the primary adsorptive mechanism, agreeing with the result obtained from pH testing. The proposed mechanism for dipyrone removal involves hydrogen bonds, pi bonds and electron donor-acceptor complex. Conclusion(s): The results are promising in comparison with recent literature and solve two environmental problems: biomass bottom ash disposal and pharmaceutical removal in aqueous medium. The ash may be regarded as a low-cost and environmentally friendly adsorbent. © 2023 Society of Chemical Industry (SCI).

In-silico Discovery of Fungal Metabolites Bergenin, Quercitrin and Dihy-droartemisinin as Potential Inhibitors against Main Protease of SARS-CoV-2

Background: Emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has given rise to COVID-19 pandemic, which has become a wreaking havoc worldwide. Therefore, there is an urgent need to find out novel drugs to combat SARS-CoV-2 in-fection. In this backdrop, the present study aimed to assess potent bioactive compounds from different fungi as potential inhibitors of SARS-CoV-2 main protease (Mpro) using an in-silico analysis. Method(s): High-Resolution Liquid Chromatography Mass Spectrometry analysis (HR-LCMS) was used for the bioactive profiling of ethanolic crude extract of Dictyophora indusiata, Geastrum tri-plex and Cyathus stercoreus. Of which, only bergenin (D. indusiata), quercitrin (G. triplex) and di-hydroartemisinin (C. stercoreus) were selected based on their medicinal uses, binding score and the active site covered. The 6LU7, a protein crystallographic structure of SARS-CoV-2 Mpro, was docked with bergenin, quercitrin and dihydroartemisinin using Autodock 4.2. Result(s): A total of 118 bioactive compounds were analyzed from the crude extract of used fungi and identified using HR LC/MS analysis. The binding energies obtained were-7.86,-10.29 and-7.20 kcal/mol, respectively, after docking analysis. Bergenin, quercitrin and dihydroartemisinin formed hydrogen bond, electrostatic interactions and hydrophobic interactions with foremost active site amino acids THR190, GLU166, GLN189, GLY143, HIS163, HIS164, CYS145 and PHE140. Conclusion(s): Present investigation suggests that these three compounds may be used as alternative inhibitors against SARS-CoV-2 Mpro. However, further research is necessary to assess in vitro potential of these compounds. To the best of our knowledge, the present investigation reported these three bioactive compounds of fungal origin for the first time.Copyright © 2021 Bentham Science Publishers.

Discovery of Potential Inhibitors of SARS-CoV-2 (COVID-19) Main Protease (Mpro) from Nigella Sativa (Black Seed) by Molecular Docking Study

Purpose: A new human coronavirus (SARS-CoV-2), triggering pneumonia, is termed as Coronavirus Disease-19 (COVID-19). There is an alarming situation now as this new virus is spreading around the world. At present, there are no specific treatments for COVID-19. Nigella sativa is known as Prophetic Medicine as its use has been mentioned in Prophetic Hadith, as a natural remedy for all the diseases except death. Seeds and oils of N. sativa have a long history of folklore usage in various systems of medicine such as Unani and Tibb, Ayurveda and Siddha in the treatment of different diseases and ailments. The aim of this research is to provide a potential inhibitor of SARS-CoV-2 Mpro. Method(s): The Molecular docking tool was used to optimize the binding affinities of chemical constituents of N. sativa with SARS-CoV-2 Mpro. Result(s): Many constituents from N. Sativa have shown better binding affinity than reported drugs with SARS-CoV-2 Mpro i.e., the alpha-hederin, Stigmasterol glucoside, Nigellidine-4-O-sulfite, Nigellidine, Sterol-3-beta-D-glucoside, Dithymoquinone, beta-sitosterol have binding affinities (kcal/mol) of-9,-8.1,-8,-7.7,-7.7,-7.4,-7.4, and-6.9 and number of hydrogen bonds formed are 06, 04, 03, 03, 03, 00, and 01, respectively. Conclusion(s): There is rationale and pre-clinical evidence of the effectiveness of N. Sativa that it may be helpful for the treatment of COVID-19 and can serve as a potential natural candidate. However, more studies should be conducted to collect high-quality data and scientific evidence of N. Sativa to use it against COVID-19 clinically.Copyright © 2021 Bentham Science Publishers.

The emerging Omicron variant spike mutation: the relative receptor-binding domain affinity and molecular dynamics

This study aims to fill a knowledge gap in our understanding of Omicron variant receptor-binding domain (RBD) interactions with host cell receptor, angiotensin-converting enzyme 2 (ACE2). Protein-protein docking, scoring, and filtration were all performed using the HDOCK server. A coarse-grained prediction of the changes in binding free energy caused by point mutations in Omicron RBD was requested from the Binding Affinity Changes upon Mutation (BeAtMuSiC) tools. GROMACS was utilized to perform molecular dynamics simulations (MD). Within the 15 mutations in Omicron RBD, several mutations have been linked to increased receptor affinity, immunological evasion, and inadequate antibody response. Wild-type (wt) SARS-CoV-2 and its Omicron variant have 92.27% identity. Nonetheless, Omicron RBD mutations resulted in a slight increase in the route mean square deviations (RMSD) of the Omicron structural model during protein-protein docking, as evidenced by RMSDs of 0.47 and 0.85 A for the wt SARS-CoV-2 and Omicron RBD-ACE2 complexes, respectively. About five-point mutations had essentially an influence on binding free energy, namely G6D, S38L, N107K, E151A, and N158Y. The rest of the mutations were expected to reduce the binding affinity of Omicron RBD and ACE2. The MD simulation supports the hypothesis that Omicron RBD is more stably bound to ACE2 than wt SARS-CoV-2 RBD. Lower RMSD and greater radius of gyration (Rg) imply appropriate Omicron structure 3D folding and stability. However, the increased solvent accessible surface area (SASA) with a greater Omicron shape may have a different interaction with receptor binding and regulate virus entrance. Omicron RBD's mutations help it maintain its structural stability, compactness, ACE2 binding, and immune evasion.Copyright © 2022 AEPress, s.r.o.. All rights reserved.

DFT, ADMET, molecular docking and molecular dynamics studies of pyridoxal

We report in silico studies of pyridoxal, which is of interest both as a precursor for further functionalization due to the presence of the aldehyde functionality, as well as a bioactive compound. So far, the crystal structure of pyridoxal has not been reported and, thus, we have optimized its structure both under water solvation and in gas phase using the DFT calculations. Under water solvation conditions the optimized structure of pyridoxal is 7.62 kcal/mol more favorable in comparison to that in gas phase. The DFT calculations were also applied to verify optical and electronic properties of the optimized structure of pyridoxal in water. The HOMO and LUMO were revealed to subtract a set of descriptors of the so-called global chemical reactivity as well as to probe pyridoxal as a potential corrosion inhibitor for some important metals used in implants. The title compound exhibits the best electron charge transfer from the molecule to the surface of Ni and Co. Some biological properties of pyridoxal were evaluated using the respective on-line tools. Molecular docking was additionally applied to study interaction of pyridoxal with some SARS-CoV-2 proteins as well as one of the monkeypox proteins. It was established that the title compound is active against all the applied proteins with the most efficient interaction with nonstructural protein 15 (endoribonuclease) and Omicron Spike protein of SARS-CoV-2. Pyridoxal was found to be also active against the studied monkeypox protein. Interaction of pyridoxal with nonstructural protein 15 (endoribonuclease) was further studied using molecular dynamics simulation.Copyright © 2023 Indian Chemical Society

Repurposing of RdRp Inhibitors against SARS-CoV-2 through Molecular Docking Tools

In the present hour, the COVID-19 pandemic needs no introduction. There is continuous and keen research in progress in order to discover or develop a suitable therapeutic candidate/vaccine against the fatal, severe acute respiratory syndrome causing coronavirus (SARS-CoV-2). Drug repurposing is an approach of utilizing the therapeutic potentials of previously approved drugs against some new targets or pharmacological responses. In the presented work, we have evaluated the RNA dependent RNA polym-erase (RdRp) inhibitory potentials of FDA approved anti-viral drugs remdesivir, ribavirin, sofosbuvir and galidesivir through molecular docking. The studies were carried out using MOE 2019.0102 software against RdRp (PDB ID:7BTF, released on 8th April, 2020). All four drugs displayed good docking scores and significant binding interactions with the amino acids of the receptor. The docking protocol was validated by redocking of the ligands and the root mean square deviation (RMSD) value was found to be less than 2. The 2D and 3D binding patterns of the drugs were studied and evaluated with the help of poses. The drugs displayed excellent hydrogen bonding interactions within the cavity of the receptor and displayed comparable docking scores. These drugs may serve as new therapeutic candidates or leads against SARS-CoV-2.Copyright © 2020 Bentham Science Publishers.

In Silico Insight into the Inhibitory Effects of Active Antidiabetic Compounds from Medicinal Plants Against SARS-CoV-2 Replication and Post-translational Modification

Background: The recent reemergence of the coronavirus (COVID-19) caused by the virus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has prompted the search for effective treatments in the forms of drugs and vaccines. Aim(s): In this regard, we performed an in silico study on 39 active antidiabetic compounds of medicinal plants to provide insight into their possible inhibitory potentials against SARS-CoV-2 replications and post-translational modifications. Top 12 active antidiabetic compounds with potential for dual inhibition of the replications and post-translational modifications of SARS-CoV-2 were ana-lyzed. Result(s): Boswellic acids, celastrol, rutin, sanguinarine, silymarin, and withanolides expressed binding energy for 3-chymotrypsin-like protease (3CLpro) (-8.0 to-8.9 Kcal/mol), papain-like protease (PLpro) (-9.1 to-10.2 Kcal/mol), and RNA-dependent RNA polymerase (RdRp) (-8.5 to-9.1 Kcal/-mol) which were higher than the reference drugs (Lopinavir and Remdesivir) used in this study. Sanguinarine, silymarin, and withanolides are the most druggable phytochemicals among other phy-tochemicals as they follow Lipinski's rule of five analyses. Sanguinarine, silymarin, and withano-lides expressed moderate solubility with no hepatotoxicity, while silymarin and withanolides could not permeate the blood-brain barrier and showed no Salmonella typhimurium reverse mutation as-say (AMES) toxicity, unlike sanguinarine from the predictive absorption, distribution, metabolism, elimination, and toxicity (ADMET) studies. Conclusion(s): Sanguinarine, silymarin, and withanolides could be proposed for further experimental studies for their development as possible phytotherapy for the COVID-19 pandemic.Copyright © 2022 Bentham Science Publishers.

Studying the Predictive Effects of Bacterial Carotenoids in the Treatment of Endometriosis Using Virtual Screening Methods

Background: Endometriosis is a chronic inflammatory disease defined as the presence of endometrial tissue outside the uterus, which causes pelvic pain and infertility. Cytokines appear to play vital roles in the development and progression of endometriosis and associated infertility. Tumor necrosis factoralpha (TNF-alpha) is a multifunctional pro-inflammatory cytokine, responsible for autoimmune and inflammatory disorders. TNF- alpha plays an important role in endometrial physiology as well as during early implantation. In addition, this cytokine has a considerable pathophysiological function in diseases such as menorrhagia, endometriosis, or infertility due to its regulatory impact on proliferation, differentiation, and angiogenesis in the human endometrium. In women with endometriosis, TNF-alpha levels increases in peritoneal fluid and serum significantly. In the present study, we focused on finding novel small molecules that can directly block TNFalpha- hTNFR1 (human TNF receptor 1) interaction. Method(s): In this regard, TNF-alpha inhibiting capacity of natural carotenoids was investigated in terms of blocking TNF-alpha-hTNFR1 interaction with the help of a combination of in silico approaches, based on virtual screening, molecular docking, and molecular dynamics (MD) simulation. Result(s): A total of 125 carotenoids were selected out of 1204 natural molecules, based on their pharmacokinetics properties, and they all met Lipinski's rule of five. Among them, sorgomol, strigol, and orobanchol had the most favorable DELTAG with the best pharmacokinetics properties and were selected for MD simulation studies, which explored the complex stability and the impact of ligands on protein conformation. It was shown that sorgomol formed the most hydrogen bonds, resulting in the highest binding energy with the lowest RMSD and RMSF. Conclusion(s): Our results showed that sorgomol was the most appropriate candidate as a TNF-alpha inhibitor. In conclusion, the present study could serve to expand possibilities to develop new therapeutic small molecules against TNF-alpha which plays an important role in the inflammation of endometriosis.

Molecular Docking Strategy for Multi-Target Inhibitor Discovery of Selected Plant Constituents in Bauhinia Acuminata

Objective: Traditional medicine is often considered to be a kind of complementary or alternative medicine (CAM) nowadays. Therefore, documenting and identifying the herbs that are effective in treating various diseases is vital for future disease control programs. This study aims to perform a molecular docking analysis of the thirteen plant components in Bauhinia acuminata against the target proteins in lung cancer (PDB IDs: 2ITY), breast cancer (1A52), diabetes (3L4U), obesity (IT02), inflammation (5COX) and corona viral infections (6VYO). Material(s) and Method(s): All the plant components used for the present study were retrieved from the plant Bauhinia acuminata and were evaluated for their biological activity results using molinspiration. Further in-silico docking analysis was performed using AutoDock Vina software and the binding interactions were visualized using Discovery studio program. Result and Discussion: The docking scores and analysis of the interactions of the plant components with targets suggest that all the selected plant components showed excellent binding to the chosen targets when compared to that of the standard drugs. As a result of the docking process on 6 different targets, the selected plant components like Quercetin, Beta-sitosterol, and Rheagenine were observed to show good binding energy values against all the 5 targets except 6VYO as shown in (Table 9). These results can further pave the way for getting better insights in identifying and designing potential lead candidates.Copyright © 2022 University of Ankara. All rights reserved.

Molecularly imprinted polymer-modified carbon paste electrodes (MIP-CPE): A review on sensitive electrochemical sensors for pharmaceutical determinations

Recent years have been associated with the development of various sensor-based technologies in response to the undeniable need for the rapid and precise analysis of an immense variety of pharmaceuticals. In this regard, special attention has been paid to the design and fabrication of sensing platforms based on electrochemical detection methods as they can offer many advantages, such as portability, ease of use, relatively cheap instruments, and fast response times. Carbon paste electrodes (CPEs) are among the most promising conductive electrodes due to their beneficial properties, including ease of electrode modification, facile surface renewability, low background currents, and the ability to modify with different analytes. However, their widespread use is affected by the lack of sufficient selectivity of CPEs. Molecularly imprinted polymers (MIPs) composed of tailor-made cavities for specific target molecules are appealing complementary additives that can overcome this limitation. Accordingly, adding MIP to the carbon paste matrix can contribute to the required selectivity of sensing platforms. This review aims to present a categorized report on the recent research and the outcomes in the combinatory fields of MIPs and CPEs for determining pharmaceuticals in complex and simple matrices. CPEs modified with MIPs of various pharmaceutical compounds, including analgesic drugs, antibiotics, antivirals, cardiovascular drugs, as well as therapeutic agents affecting the central nervous system (CNS), will be addressed in detail.Copyright © 2023 Elsevier B.V.

Chemi-Informatic Approach to Investigate Putative Pharmacoactive Agents of Plant Origin to Eradicate COVID-19

Background: The scientific community has supported the medicinal flora of ancient as well as modern times in extracting chemicals, which holds therapeutic potential. In many previous studies, Amentoflavone discovered as an anti-viral agent, and it is present as a bioactive constituent in many plants of different families like Selaginellaceae, Euphorbiaceae, and Calophyllaceae. Withania somnifera (Ashwagandha) is already considered a significant anti-viral agent in traditional medicine, and it is the main source of Somniferine-A and Withanolide-B. Objective(s): In this study, phytochemicals such as withanolide-b, somniferine-a, stigmasterol, amentoflavone, and chavicine were analyzed to screen protein inhibitors, out of them;such proteins are involved in the internalization and interaction of SARS-CoV-2 with human cytological domains. This will help in developing a checkpoint for SARS-CoV-2 internalization. Method(s): Chemi-informatic tools like basic local alignment search tool (BLAST), AutoDock-vina, SwissADME, MDWeb, Molsoft, ProTox-II, and LigPlot were used to examine the action of pharmacoactive agents against SARS-CoV-2. The tools used in the study were based on the finest algorithms like artificial neural networking, machine learning, and artificial intelligence. Result(s): On the basis of binding energies less than equal to-8.5 kcal/mol, amentoflavone, stigmasterol, and somniferine-A were found to be the most effective against COVID-19 disease as these chemical agents exhibit hydrogen bond interactions and competitively inhibit major proteins (SARS-CoV-2 Spike, Human ACE-2 receptor, Human Furin protease, SARS-CoV-2 RNA binding protein) that are involved in its infection and pathogenesis. Simulation analysis provides more validity to the selection of the drug candidate Amentoflavone. ADMET properties were found to be in the feasible range for putative drug candidates. Conclusion(s): Computational analysis was successfully used for searching pharmacoactive phytochemicals like Amentoflavone, Somniferine-A, and Stigmasterol that can bring control over COVID-19 expansion. This new methodology was found to be efficient, as it reduces monetary expenditures and time consumption. Molecular wet-lab validations will provide approval for finalizing our selected drug model for controlling the COVID-19 pandemic.Copyright © 2022 Bentham Science Publishers.

Recent advances of nanotechnology in COVID 19: A critical review and future perspective

The global anxiety and economic crisis causes the deadly pandemic coronavirus disease of 2019 (COVID 19) affect millions of people right now. Subsequently, this life threatened viral disease is caused due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, morbidity and mortality of infected patients are due to cytokines storm syndrome associated with lung injury and multiorgan failure caused by COVID 19. Thereafter, several methodological advances have been approved by WHO and US-FDA for the detection, diagnosis and control of this wide spreadable communicable disease but still facing multi-challenges to control. Herein, we majorly emphasize the current trends and future perspectives of nano-medicinal based approaches for the delivery of anti-COVID 19 therapeutic moieties. Interestingly, Nanoparticles (NPs) loaded with drug molecules or vaccines resemble morphological features of SARS-CoV-2 in their size (60–140 nm) and shape (circular or spherical) that particularly mimics the virus facilitating strong interaction between them. Indeed, the delivery of anti-COVID 19 cargos via a nanoparticle such as Lipidic nanoparticles, Polymeric nanoparticles, Metallic nanoparticles, and Multi-functionalized nanoparticles to overcome the drawbacks of conventional approaches, specifying the site-specific targeting with reduced drug loading and toxicities, exhibit their immense potential. Additionally, nano-technological based drug delivery with their peculiar characteristics of having low immunogenicity, tunable drug release, multidrug delivery, higher selectivity and specificity, higher efficacy and tolerability switch on the novel pathway for the prevention and treatment of COVID 19. © 2022 The Author(s)

Computational tools for aptamer identification and optimization

Aptamers are single-stranded DNA or RNA oligonucleotides that can selectively bind to a specific target. They are generally obtained by SELEX, but the procedure is challenging and time-consuming. Moreover, the identified aptamers tend to be insufficient in stability, specificity, and affinity. Thus, only a handful of aptamers have entered the practical use stage. Recently, computational approaches have demonstrated a significant capacity to assist in the discovery of high-performance aptamers. This review discusses the advances achieved in several aspects of computational tools in this field, as well as the new progress in machine learning and deep learning, which are used in aptamer identification and optimization. To illustrate these computationally aided processes, aptamer selections against SARS-CoV-2 are discussed in detail as a case study. We hope that this review will aid and motivate researchers to develop and utilize more computational techniques to discover ideal aptamers effectively. Copyright © 2022 Elsevier B.V.

Computational Method on Hydroxychloroquine and Azithromycin for SARS-CoV-2: Binding Affinity Studies

World is facing a new pandemic called covid-19SARS-CoV-2) since a year ago. Unfortunately there is no treatment for Covid 19 nowadays as well as no potential therapies has been developed to overcome from coronavirus pandemic. Some potential drug molecules with combination have ability to respond for covid19 virus. From the research it was found that the reduction of viral load can be treated with hydroxychloroquine and azithromycin combination. We evaluate the mode of interactions of hydroxychloroquine and azithromycin with the dynamic site of SARS-CoV-2 coronavirus main protease. Molecular Structure-based computational approach viz. molecular docking simulations were performed to scale up their affinity and binding fitness of the docked complex of novel SARS-CoV-2 coronavirus protease and hydroxychloroquine and azithromycin. The natural inhibitor N3 of novel SARS-CoV-2 coronavirus protease were exhibited highest affinity in terms of MolDock score (-167.203Kcal/mol), and hydroxychloroquine was found with lowest target affinity (-55.917 Kcal/mol).The amino acid residue cysteine 145 and histidine 41 is bound covalently and formed hydrogen bond interaction with SARS-CoV-2 inhibitor known as inhibitor N3 as such, hydroxychloroquine and azithromycin also formed hydrogen bond interaction. The binding patterns of the inhibitor N3 of SARS-CoV-2 coronavirus main protease could be used as a guideline for medicinal chemist to explore their SARS-CoV-2 inhibitory potential. Copyright © RJPT All right reserved.