Advancements in COVID- 19 Testing: An in-depth overview.

COVID-19 rapidly evolved as a pandemic, killing and hospitalising millions of people, creating unprecedented hurdles for communities and health care systems worldwide. The rapidly evolving pandemic prompted the head of the World Health Organisation to deliver a critical message: "test, test, test." The response from the diagnostic industry and researchers worldwide was overwhelming, resulting in more than a thousand commercial tests available in the market worldwide. Several sampling approaches and diagnostic techniques have been employed from the early stages of the pandemic, such as SARS-CoV-2 detection by targeting the viral RNA or protein, indirectly via antibody testing, biochemical estimation, and various imaging techniques, and many are still in the various stages of development and yet to be marketed. Accurate testing techniques and appropriate sampling are the need of the hour to manage, diagnose and treat the pandemic, especially in the current crisis, where SARS-CoV-2 undergoes constant mutation, evolving into various strains, which are pretty challenging. The article discusses various testing techniques as well as screening methods for detection, treatment, and management of COVID-19 transmission, such as NAAT, PCR, isothermal detection including RT-LAMP, RPA, NASBA, RCA, SDA, NEAR, and TMA, CRISPR strategy, nanotechnology approach, metagenomic profiling, point of care tests, virus neutralization test, ELISA, biomarker estimation, utilization of imaging techniques such as CT, ultrasonography, brain MRI in COVID-19 complications, and other novel strategies including microarray methods, microfluidic methods and artificial intelligence with an emphasis on advancements in the testing strategies for the diagnosis, management, and prevention of COVID-19.

Exploring the inhibitory potential of novel piperidine-derivatives against main protease (Mpro) of SARS-CoV-2: A hybrid approach consisting of molecular docking, MD simulations and MMPBSA analysis

Graphical In the current study, a hybrid computational approach consisting of different computational methods to explore the molecular electronic structures, bioactivity and therapeutic potential of piperidine compounds against SARS-CoV-2. The quantum chemical methods are used to study electronic structures of designed derivatives, molecular docking methods are used to see the most potential docking interactions for main protease (MPro) of SARS-CoV-2 while molecular dynamic and MMPBSA analyses are performed in bulk water solvation process to mimic real protein like aqueous environment and effectiveness of docked complexes. We designed and optimized piperidine derivatives from experimentally known precursor using quantum chemical methods. The UV-Visible, IR, molecular orbitals, molecular electrostatic plots, and global chemical reactivity descriptors are carried out which illustrate that the designed compounds are kinetically stable and reactive. The results of MD simulations and binding free energy revealed that all the complex systems possess adequate dynamic stability, and flexibility based on their RMSD, RMSF, radius of gyration, and hydrogen bond analysis. The computed net binding free energy

CRISPR-Cas13a-powered electrochemical biosensor for the detection of the L452R mutation in clinical samples of SARS-CoV-2 variants.

Since the end of 2019, a highly contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has deprived numerous lives worldwide, called COVID-19. Up to date, omicron is the latest variant of concern, and BA.5 is replacing the BA.2 variant to become the main subtype rampaging worldwide. These subtypes harbor an L452R mutation, which increases their transmissibility among vaccinated people. Current methods for identifying SARS-CoV-2 variants are mainly based on polymerase chain reaction (PCR) followed by gene sequencing, making time-consuming processes and expensive instrumentation indispensable. In this study, we developed a rapid and ultrasensitive electrochemical biosensor to achieve the goals of high sensitivity, the ability of distinguishing the variants, and the direct detection of RNAs from viruses simultaneously. We used electrodes made of MXene-AuNP (gold nanoparticle) composites for improved sensitivity and the CRISPR/Cas13a system for high specificity in detecting the single-base L452R mutation in RNAs and clinical samples. Our biosensor will be an excellent supplement to the RT-qPCR method enabling the early diagnosis and quick distinguishment of SARS-CoV-2 Omicron BA.5 and BA.2 variants and more potential variants that might arise in the future.

Design and in silico investigation of novel Maraviroc analogues as dual inhibition of CCR-5/SARS-CoV-2 Mpro.

A sudden increase in life-threatening COVID-19 infections around the world inflicts global crisis and emotional trauma. In current study two druggable targets, namely SARS-COV-2 Mpro and CCR-5 were selected due to their significant nature in the viral life cycle and cytokine molecular storm respectively. The systematic drug repurposing strategy has been utilized to recognize inhibitory mechanism through extensive in silico investigation of novel Maraviroc analogues as promising inhibitors against SARS-CoV-2 Mpro and CCR-5. The dual inhibition specificity approach implemented in present study using molecular docking, molecular dynamics (MD), principal component analysis (PCA), free energy landscape (FEL) and MM/PBSA binding energy studies. The proposed Maraviroc analogues obtained from in silico investigation could be easily synthesized and constructive in developing significant drug against COVID-19 pandemic, with essentiality of their in vivo/in vitro evaluation to affirm the conclusions of this study. This will further fortify the concept of single drug targeting dual inhibition mechanism for treatment of COVID-19 infection and complications.

In silico evaluation of NO donor heterocyclic vasodilators as SARS-CoV-2 Mpro protein inhibitor.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes COVID-19 disease has been exponentially increasing throughout the world. The mortality rate is increasing gradually as effective treatment is unavailable to date. In silico based screening for novel testable hypotheses on SARS-CoV-2 Mpro protein to discover the potential lead drug candidate is an emerging area along with the discovery of a vaccine. Administration of NO-releasing agents, NO inducers or the NO gas itself may be useful as therapeutics in the treatment of SARS-CoV-2. In the present study, a 3D structure of SARS-CoV-2 Mpro protein was used for the rational setting of inhibitors to the binding pocket of enzyme which proposed that phenyl furoxan derivative gets efficiently dock in the target pocket. Molecular docking and molecular dynamics simulations helped to investigate possible effective inhibitor candidates bound to SARS-CoV-2 Mpro substrate binding pocket. Molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) calculations revealed energetic contributions of active site residues of Mpro in binding with most stable proposed NO donor heterocyclic vasodilator inhibitor molecules. Furthermore, principal component analysis (PCA) showed that the NO donor heterocyclic inhibitor molecules 14, 16, 18 and 19 was strongly bound to catalytic core of SARS-CoV-2 Mpro protein, limiting its movement to form stable complex as like control. Thus, overall in silico investigations revealed that 5-oxopiperazine-2-carboxylic acid coupled furoxan derivatives was found to be key pharmacophore in drug design for the treatment of SARS-CoV-2, a global pandemic disease with a dual mechanism of action as NO donor and a worthwhile ligand to act as SARS-CoV-2 Mpro protein inhibitor.Communicated by Ramaswamy H. Sarma.

Are Antisense Long Non-Coding RNA Related to COVID-19?

Fighting external pathogens relies on the tight regulation of the gene expression of the immune system. Ferroptosis, which is a distinct form of programmed cell death driven by iron, is involved in the enhancement of follicular helper T cell function during infection. The regulation of RNA is a key step in final gene expression. The present study aimed to identify the expression level of antisense lncRNAs (A2M-AS1, DBH-AS1, FLVCR1-DT, and NCBP2AS2-1) and FLVCR1 in COVID-19 patients and its relation to the severity of the disease. COVID-19 patients as well as age and gender-matched healthy controls were enrolled in this study. The expression level of the antisense lncRNAs was measured by RT-PCR. Results revealed the decreased expression of A2M-AS1 and FLVCR1 in COVID-19 patients. Additionally, they showed the increased expression of DBH-AS1, FLVCR1-DT, and NCBP2AS2. Both FLVCR1-DT and NCBP2AS2 showed a positive correlation with interleukin-6 (IL-6). DBH-AS1 and FLVCR1-DT had a significant association with mortality, complications, and mechanical ventilation. A significant negative correlation was found between A2M-AS1 and NCBP2AS2-1 and between FLVCR1 and FLVCR1-DT. The study confirmed that the expression level of the antisense lncRNAs was deregulated in COVID-19 patients and correlated with the severity of COVID-19, and that it may have possible roles in the pathogenesis of this disease.

A CRISPR/Cas12a-empowered surface plasmon resonance platform for rapid and specific diagnosis of the Omicron variant of SARS-CoV-2.

The outbreak of the COVID-19 pandemic was partially due to the challenge of identifying asymptomatic and presymptomatic carriers of the virus, and thus highlights a strong motivation for diagnostics with high sensitivity that can be rapidly deployed. On the other hand, several concerning SARS-CoV-2 variants, including Omicron, are required to be identified as soon as the samples are identified as 'positive'. Unfortunately, a traditional PCR test does not allow their specific identification. Herein, for the first time, we have developed MOPCS (Methodologies of Photonic CRISPR Sensing), which combines an optical sensing technology-surface plasmon resonance (SPR) with the 'gene scissors' clustered regularly interspaced short palindromic repeat (CRISPR) technique to achieve both high sensitivity and specificity when it comes to measurement of viral variants. MOPCS is a low-cost, CRISPR/Cas12a-system-empowered SPR gene-detecting platform that can analyze viral RNA, without the need for amplification, within 38 min from sample input to results output, and achieve a limit of detection of 15 fM. MOPCS achieves a highly sensitive analysis of SARS-CoV-2, and mutations appear in variants B.1.617.2 (Delta), B.1.1.529 (Omicron) and BA.1 (a subtype of Omicron). This platform was also used to analyze some recently collected patient samples from a local outbreak in China, identified by the Centers for Disease Control and Prevention. This innovative CRISPR-empowered SPR platform will further contribute to the fast, sensitive and accurate detection of target nucleic acid sequences with single-base mutations.

CRISPR-Cas12a-Empowered Electrochemical Biosensor for Rapid and Ultrasensitive Detection of SARS-CoV-2 Delta Variant.

Coronavirus disease 2019 (COVID-19) is a highly contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The gold standard method for the diagnosis of SARS-CoV-2 depends on quantitative reverse transcription-polymerase chain reaction till now, which is time-consuming and requires expensive instrumentation, and the confirmation of variants relies on further sequencing techniques. Herein, we first proposed a robust technique-methodology of electrochemical CRISPR sensing with the advantages of rapid, highly sensitivity and specificity for the detection of SARS-CoV-2 variant. To enhance the sensing capability, gold electrodes are uniformly decorated with electro-deposited gold nanoparticles. Using DNA template identical to SARS-CoV-2 Delta spike gene sequence as model, our biosensor exhibits excellent analytical detection limit (50 fM) and high linearity (R2 = 0.987) over six orders of magnitude dynamic range from 100 fM to 10 nM without any nucleic-acid-amplification assays. The detection can be completed within 1 h with high stability and specificity which benefits from the CRISPR-Cas system. Furthermore, based on the wireless micro-electrochemical platform, the proposed biosensor reveals promising application ability in point-of-care testing.

Synthesis, spectral characterization, crystal structure and computational investigation of 2-formyl-6-methoxy-3-carbethoxy quinoline as potential SARS-CoV inhibitor.

The recent COVID-19 outbreak caused by the novel coronavirus SARS-CoV-2 has an immense impact on global health and economy. Although vaccines are being used, urgent need of drugs based on natural products with high efficacy and safety is a pressing priority. Quinoline alkaloids are well known for their therapeutic action against malaria; initially, it was tried against Coronaviruses. It is a basic vital scaffold to design drugs with required biological and pharmacological activities. In this present study, a new quinoline compound was synthesized and characterized by spectroscopy techniques. Crystal structure was established by SCXRD analysis and data is used as an input to perform various computations. Additionally, using state-of-the-art quantum computational techniques, the geometry optimization and calculation of UV-Vis spectrum of 2F6M3CQ were performed at B3LYP/6-311G* level of theory. The optimized molecular geometric parameters as well as UV-Vis spectrum values are found to be in good agreement with their respective experimental results. The visualization of 3-D plots of FMO and MEP indicated the structure and reactivity trends of 2F6M3CQ molecule. Molecular docking methods were utilized to find the drug ability of 2F6M3CQ with Mproprotein of SARS-CoV-2. There were many intermolecular interactions between Mpro protein and 2F6M3CQ molecule which lead to good binding energy (-5.5 kcal/mol) between them which was found to be better than the binding energy of chloroquinine molecule (-4.5 kcal/mol) as studied under same docking protocols. Finally, drug likeness and ADME properties of 2F6M3CQ were also analyzed. There is no violation found for RO5 in our 2F6M3CQ compound. ADME analysis shows drug like properties of compound 2F6M3CQ which predicts that it might be a potential candidate for inhibition of SARS-CoV-2.

Insighting isatin derivatives as potential antiviral agents against NSP3 of COVID-19.

The world is now facing intolerable damage in all sectors of life because of the deadly COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2. The discovery and development of anti-SARS-CoV-2 drugs have become pragmatic in the time needed to fight against this pandemic. The non-structural protein 3 is essential for the replication of transcriptase complex (RTC) and may be regarded as a possible target against SARS-CoV-2. Here, we have used a comprehensive in silico technique to find potent drug molecules against the NSP3 receptor of SARS-CoV-2. Virtual screening of 150 Isatin derivatives taken from PubChem was performed based on their binding affinity estimated by docking simulations, resulting in the selection of 46 ligands having binding energy greater than -7.1 kcal/mol. Moreover, the molecular interactions of the nine best-docked ligands having a binding energy of ≥ -8.5 kcal/mol were analyzed. The molecular interactions showed that the three ligands (S5, S16, and S42) were stabilized by forming hydrogen bonds and other significant interactions. Molecular dynamic simulations were performed to mimic an in vitro protein-like aqueous environment and to check the stability of the best three ligands and NSP3 complexes in an aqueous environment. The binding energy of the S5, S16, and S42 systems obtained from the molecular mechanics Poisson-Boltzmann surface area also favor the system's stability. The MD and MM/PBSA results explore that S5, S16, and S42 are more stable and can be considered more potent drug candidates against COVID-19 disease. Supplementary Information: The online version contains supplementary material available at 10.1007/s11696-022-02298-7.

Precise and Prompt Analyte Detection via Ordered Orientation of Receptor in WSe2-Based Field Effect Transistor.

Field-effect transistors (FET) composed of transition metal dichalcogenide (TMDC) materials have gained huge importance as biosensors due to their added advantage of high sensitivity and moderate bandgap. However, the true potential of these biosensors highly depends upon the quality of TMDC material, as well as the orientation of receptors on their surfaces. The uncontrolled orientation of receptors and screening issues due to crossing the Debye screening length while functionalizing TMDC materials is a big challenge in this field. To address these issues, we introduce a combination of high-quality monolayer WSe2 with our designed Pyrene-based receptor moiety for its ordered orientation onto the WSe2 FET biosensor. A monolayer WSe2 sheet is utilized to fabricate an ideal FET for biosensing applications, which is characterized via Raman spectroscopy, atomic force microscopy, and electrical prob station. Our construct can sensitively detect our target protein (streptavidin) with 1 pM limit of detection within a short span of 2 min, through a one-step functionalizing process. In addition to having this ultra-fast response and high sensitivity, our biosensor can be a reliable platform for point-of-care-based diagnosis.

Synthesis, Characterization, Biological Activity and Molecular Docking Studies of Novel Organotin(IV) Carboxylates.

Four new carboxylates complexes with general formula R2SnL2 and R3SnL, where R = n-butyl (1, 3), methyl (2, 4) and L = 4-Chlorophenoxyacetate, were synthesized in significant yields. FT-IR analysis revealed a chelating (1 and 2) and a bridging bidentate (3 and 4) coordination modes for the carboxylate ligand in solid state which was further confirmed by the single crystal X-ray analysis of complex 4. The NMR data (1H, 13C and 119Sn) revealed a higher coordination number around the tin center in R2SnL2 (1 and 2) compared to R3SnL (3 and 4). A close matching was observed between the experimental and calculated structures (obtained at B3LYP/6-31G* + LANL2DZ basis set). Quantum chemical analysis indicates that the carboxylate moiety has the major contribution in the formation of filled and unfilled orbitals as well as in ligand to ligand intramolecular charge transfer during the electronic transitions. The cytotoxicity data of the screened compounds evaluated against lung cancer cell line (A549) and normal lung fibroblast cell line (MRC-5) revealed that 1, 3 and 4 have shown dose dependent cytotoxic effects while HL and 2 have shown steady and low cytotoxic activities. The antibacterial activity of complexes 1-4 is higher than that of HL. Molecular docking study showed an intercalation binding mode for complex 3 with DNA (docking score = -3.6005) involving four polar interactions. Complex 3 docking with tubulin (PDB ID 1SA0) with colchicine as a target protein resulted in three polar interactions (docking score -5.2957). Further, the docking analysis of the HL and 1-4 has shown an adequate interactions with the coronavirus SARS-CoV-2 spike protein, nucleocapsid protein and human angiotensin converting enzyme (ACE2).

Insighting the Therapeutic Potential of Fifty (50) Shogaol Derivatives Against Mpro of SARS-CoV-2

SARS-CoV-2, which causes COVID-19 disease, has proven to be a disastrous pandemic due to its contagious nature. This study has been planned to theoretically explore some antidotes against this virus from natural compounds. A total of 150 compounds from the shogaol class and shogaol derivatives (SDs) have been screened whereas 50 among those, which obeyed Lipinski’s Rule of Five (Ro5), have further been investigated using molecular docking techniques. Furthermore, reference antiviral drug chloroquine (ChQ) and Co-Crystallized inhibitor have also been studied against Mpro of SARS-CoV-2 for comparing the potential of our docked ligands. Surprisingly, 78% of our docked ligands have shown binding energies and inhibition constants lower than ChQ and all ligands showed these values lower than an inhibitor. We further visualized the nature of intermolecular interactions for the best docked six ligands, which have shown higher binding affinities. We have also assessed ADMET properties for three ligands that displayed visually the best intermolecular interactions. Quantum analysis of three selected ligands L4, L5, and L9 has proved their reactivity and kinetic stability. Moreover, molecular dynamic simulations over 60ns have been run for free Mpro and its selected three ligand-protein complexes for evaluating conformational stability and residual flexibility of docked complexes. Furthermore, 100ns the MD simulations have been performed for two ligand complexes L4, L5 (with negative binding free energy), and inhibitor. Available parameters suggest stable complexes for our ligands and could be active drugs against SARS-CoV-2 in near future. [ FROM AUTHOR] Copyright of Journal of Computational Biophysics & Chemistry is the property of World Scientific Publishing Company 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.)

Insighting the optoelectronic, charge transfer and biological potential of benzo-thiadiazole and its derivatives.

The current investigation applies the dual approach containing quantum chemical and molecular docking techniques to explore the potential of benzothiadiazole (BTz) and its derivatives as efficient electronic and bioactive materials. The charge transport, electronic and optical properties of BTz derivatives are explored by quantum chemical techniques. The density functional theory (DFT) and time dependent DFT (TD-DFT) at B3LYP/6-31G** level of theory utilized to optimize BTz and newly designed ligands at the ground and first excited states, respectively. The heteroatoms substitution effects on different properties of 4,7-bis(4-methylthiophene-2yl) benzo[c] [1,2,5]thiadiazole (BTz2T) as initial compound are studied at molecular level. Additionally, we also study the possible inhibition potential of COVID-19 from benzothiadiazole (BTz) containing derivatives by implementing the grid based molecular docking methods. All the newly designed ligands docked with the main protease (MPRO:PDB ID 6LU7) protein of COVID-19 through molecular docking methods. The studied compounds showed strong binding affinities with the binding site of MPRO ranging from -6.9 to -7.4 kcal/mol. Furthermore, the pharmacokinetic properties of the ligands are also studied. The analysis of these results indicates that the studied ligands might be promising drug candidates as well as suitable for photovoltaic applications.

Computational Study on the Inhibitory Effect of Natural Compounds against the SARS-CoV-2 Proteins.

COVID-19 is more virulent and challenging to human life. In India, the Ministry of AYUSH recommended some strategies through Siddha, homeopathy, and other methods to effectively manage COVID-19 (Guidelines for AYUSH Clinical Studies in COVID-19, 2020). Kabasura Kudineer and homeopathy medicines are in use for the prevention and treatment of COVID-19 infection; however, the mechanism of action is less explored. This study aims to understand the antagonist activity of natural compounds found in Kabasura Kudineer and homeopathy medicines against the SARS-CoV-2 using computational methods. Potential compounds were screened against NSP-12, NSP-13, NSP-14, NSP-15, main protease, and spike proteins. Structure-based virtual screening results shows that, out of 14,682 Kabasura Kudineer compounds, the 250395, 129677029, 44259583, 44259584, and 88583189 compounds and, out of 3,112 homeopathy compounds, the 3802778, 320361, 5315832, 14590080, and 74029795 compounds have good scoring function against the SARS-CoV-2 structural and nonstructural proteins. As a result of docking, homeopathy compounds have a docking score ranging from -5.636 to 13.631 kcal/mol, while Kabasura Kudineer compounds have a docking score varying from -8.290 to -13.759 kcal/mol. It has been found that the selected compounds bind well to the active site of SARS-CoV-2 proteins and form hydrogen bonds. The molecular dynamics simulation study shows that the selected compounds have maintained stable conformation in the simulation period and interact with the target. This study supports the antagonist activity of natural compounds from Kabasura Kudineer and homeopathy against SARS-CoV-2's structural and nonstructural proteins.

Identification of phytochemical inhibitors of SARS-CoV-2 protease 3CLpro from selected medicinal plants as per molecular docking, bond energies and amino acid binding energies.

Recent worldwide outbreak of SARS-COV-2 pandemic has increased the thirst to discover and introduce antiviral drugs to combat it. The bioactive compounds from plant sources, especially terpenoid have protease inhibition activities so these may be much effective for the control of viral epidemics and may reduce the burden on health care system worldwide. Present study aims the use of terpenoid from selected plant source through bioinformatics tools for the inhibition of SARS-COV-2. This study is based on descriptive analysis. The Protein Data Bank and PubChem database were used for the analysis of SARS-COV-2 protease and plant source terpenoids. Molecular docking by using molegro virtual docker (MVD) software was carried out. The findings of study are based on the inhibitory actions of different plant sourced terpenoid against SARS-COV-2. As per the available resources and complementary analysis these phytochemicals have capacity to inhibit 3CLpro protease. The study reports that (3,3-dimethylally) isoflavone (Glycine max), licoleafol (Glycyrrhiza uralensis), myricitrin (Myrica cerifera), thymoquinone (Nigella sativa), bilobalide, ginkgolide A (Ginkgo biloba), Salvinorin A (Salvia divinorum), citral (Backhousia citriodora) and prephenazine (drug) showed high activity against SARS-COV-2 protease 3CLpro. The drug like and ADMET properties revealed that these compounds can safely be used as drugs. Cross structural analysis by using bioinformatics study concludes that these plant source terpenoid compounds can be effectively used as antiprotease drugs for SARS-COV-2 in future.

Critical role of nitric oxide in impeding COVID-19 transmission and prevention: a promising possibility.

COVID-19 is a serious respiratory infection caused by a beta-coronavirus that is closely linked to SARS. Hypoxemia is a symptom of infection, which is accompanied by acute respiratory distress syndrome (ARDS). Augmenting supplementary oxygen may not always improve oxygen saturation; reversing hypoxemia in COVID-19 necessitates sophisticated means to promote oxygen transfer from alveoli to blood. Inhaled nitric oxide (iNO) has been shown to inhibit the multiplication of the respiratory coronavirus, a property that distinguishes it from other vasodilators. These findings imply that NO may have a crucial role in the therapy of COVID-19, indicating research into optimal methods to restore pulmonary physiology. According to clinical and experimental data, NO is a selective vasodilator proven to restore oxygenation by helping to normalize shunts and ventilation/perfusion mismatches. This study examines the role of NO in COVID-19 in terms of its specific physiological and biochemical properties, as well as the possibility of using inhaled NO as a standard therapy. We have also discussed how NO could be used to prevent and cure COVID-19, in addition to the limitations of NO.

Exploring the inhibitory potential of novel bioactive compounds from mangrove actinomycetes against nsp10 the major activator of SARS-CoV-2 replication.

The current study reveals the inhibitory potential of novel bioactive compounds of mangrove actinomycetes against nsp10 of SARS-CoV-2. A total of fifty (50) novel bioactive (antibacterial, antitumor, antiviral, antioxidant, and anti-inflammatory) compounds of mangrove actinomycetes from different chemical classes such as alkaloids, dilactones, sesquiterpenes, macrolides, and benzene derivatives are used for interaction analysis against nsp10 of SARS-CoV-2. The six antiviral agents sespenine, xiamycin c, xiamycin d, xiamycin e, xiamycin methyl ester, and xiamycin A (obeyed RO5 rule) are selected based on higher binding energy, low inhibition constant values, and better-docked positions. The effective hydrogen and hydrophobic (alkyl, π -sigma, π - π T shaped and π -alkyl) interaction analysis reveals the four antivirals sespenine, xiamycin C, xiamycin methyl ester, and xiamycin A are supposed to be the most auspicious inhibitors against nsp10 of SARS-CoV-2. Quantum chemistry methods such as frontier molecular orbitals and molecular electrostatic potential are used to explain the thermal stability and chemical reactivity of ligands. The toxicity profile shows that selected ligands are safe by absorption, distribution, metabolism, excretion, and toxicity profiling and also effective for inhibition of nsp10 protein of SARS-CoV-2. The molecular dynamic simulation investigation of apo and halo forms of nsp10 done by RMSD of C α atoms of nsp10, all amino acid residues RMSF, count total number of hydrogen bonds and radius of gyration (R g). MD simulations reveal the complexes are stable and increase the structural compactness of nsp10 in the binding pocket. The lead antiviral compounds sespenine, xiamycin C, xiamycin methyl ester, and xiamycin A are recommended as the most promising inhibitors against nsp10 of SARS-CoV-2 pathogenicity. Supplementary Information: The online version contains supplementary material available at 10.1007/s11696-021-01997-x.

Shedding Light on the Synthesis, Crystal Structure, Characterization, and Computational Study of Optoelectronic Properties and Bioactivity of Imine derivatives.

Two imine compounds named as (E)-2-(((3,4-dichlorophenyl)imino)methyl)phenol (DC2H) and (E)-4-(((2,4-dimethylphenyl)imino)methyl)phenol (DM4H) are synthesized, and their crystal structures are verified using the single-crystal X-ray diffraction (XRD) technique. The crystal structures of the compounds are compared with the closely related crystal structures using the Cambridge Structural Database (CSD). The crystal packing in terms of intermolecular interactions is fully explored by Hirshfeld surface analysis. Void analysis is carried out for both compounds to check the strength of the crystal packing. Furthermore, a state-of-the-art dual computational technique consisting of quantum chemical and molecular docking methods is used to shed light on the molecular structure, optoelectronic properties, and bioactivity of indigenously synthesized compounds. The optimized molecular geometries are compared with their counterpart experimental values. Based on previous reports of biofunctions of the indigenously synthesized imine derivatives, they are explored for their potential inhibition properties against two very crucial proteins (main protease (Mpro) and nonstructural protein 9 (NSP9)) of SARS-CoV-2. The calculated interaction energy values of DC2H and DM4H with Mpro are found to be -6.3 and -6.6 kcal/mol, respectively, and for NSP9, the calculated interaction energy value is found to be -6.5 kcal/mol. We believe that the current combined study through experiments and computational techniques will not only pique the interest of the broad scientific community but also evoke interest in their further in vitro and in vivo investigations.

Synthesis and characterization of ferrocene-based thiosemicarbazones along with their computational studies for potential as inhibitors for SARS-CoV-2

Ferrocene and its derivatives are vital class of organometallic compounds having extensive biological activities. Six novel ferrocene-based thiosemicarbazones have been synthesized through the condensation reaction of acetyl ferrocene with differently substituted thiosemicarbazide. Furthermore, we used state-of-the-art computational docking approach to explore the theoretical aspects for possible antiviral potential of our synthesized compounds. All the six compounds were docked with Mpro protein of SARS-CoV-2, which is very crucial protein for viral replication. Among the six derivatives, compounds 2 and 4 showed higher binding affinities with binding energy of − 6.7 and − 6.9 kcal/mol, respectively. The visualization of intermolecular interactions between synthesized derivatives and Mpro protein illustrated that each of compounds 2 and 4 forms two hydrogen bonds accompanied by important hydrophobic interactions. The comparison of binding affinities with some recently approved drugs like remdesivir, chloroquine and hydroxychloroquine molecules are also made. The calculated binding energies of remdesivir, chloroquine and hydroxychloroquine molecules with Mpro of COVID-19 was found to be − 7.00, − 5.20 and − 5.60 kcal/mol, respectively. The binding energy of compound 4 (− 6.9 kcal/mol) was almost equal to the remdesivir and greater than the binding energies of chloroquine and hydroxychloroquine. It is expected from the current investigation that our synthesized ferrocene-based thiosemicarbazones might have potential for drug against SARS-CoV-2.