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Researchers have reported some useful information about the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leading to CoV disease 2019 (COVID-19). Several studies have been performed in order to develop antiviral drugs, from which a few have been prescribed to patients. Also, several diagnostic tests have been designed to accelerate the process of identifying and treating COVID-19. It has been well-documented that the surface of host cells is covered by some receptors, known as angiotensin-converting enzyme 2 (ACE2), which mediates the binding and entry of CoV. After entering, the viral RNA interrupts the cell proliferation system to activate self-proliferation. However, having all the information about the outbreakof the SARS-COV-2, it is not still clear which factors determine the severity of lung and heart function impairment induced by COVID-19. A major step in exploring SARS-COV-2 pathogenesis is to determine the distribution of ACE2 in different tissues . In this review, the structure and origin of CoV, the role of ACE2 as a receptor of SARS-COV-2 on the surface of host cells, and the ACE2 distribution in different tissues with a focus on lung and cardiovascular system have been discussed. It was also revealed that acute and chronic cardiovascular diseases (CVDs) may result in the clinical severity of COVID-19. In conclusion, this review may provide useful information in developing some promising strategies to end up with a worldwide COVID-19 pandemic.Communicated by Ramaswamy H. Sarma.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative representative of a severe respiratory illness resulted in widespread human infections and deaths in nearly all of the countries since late 2019. There is no therapeutic FDA-approved drug against SARS-CoV-2 infection, although a combination of anti-viral drugs is directly being practiced in some countries. A broad-spectrum of antiviral agents are being currently evaluated in clinical trials, and in this review, we specifically focus on the application of Remdesivir (RVD) as a potential anti-viral compound against Middle East respiratory syndrome (MERS) -CoV, SARS-CoV and SARS-CoV-2. First, we overview the general information about SARS-CoV-2, followed by application of RDV as a nucleotide analogue which can potentially inhibits RNA-dependent RNA polymerase of COVs. Afterwards, we discussed the kinetics of SARS- or MERS-CoV proliferation in animal models which is significantly different compared to that in humans. Finally, some ongoing challenges and future perspective on the application of RDV either alone or in combination with other anti-viral agents against CoVs infection were surveyed to determine the efficiency of RDV in preclinical trials. As a result, this paper provides crucial evidence of the potency of RDV to prevent SARS-CoV-2 infections.Communicated by Ramaswamy H. Sarma.

In the present work, we studied the structure-activity relationship and kinetics of thermal inactivation of α-glucosidase A (AglA) in a 50 mM potassium phosphate buffer at pH 6.8 using p -nitrophenyl α-d-glucopyranoside ( p NPG) as the synthetic substrate following absorbance at 410 nm by UV-Vis spectrophotometer. The interface structure and residual activity plot were analyzed via biochemical measurements by means of conformational lock theory, as well. The thermal inactivation curves were plotted in temperature interval from 30 to 50 °C. Based on experimental and structural data we suggested intermediates during inactivation before the loss of enzyme activity. Arrhenius plot for thermal inactivation rate constant showed biphasic appearance related to before and after 45°C temperature. The contact areas between two subunits were ruptured and unlocked stepwise during dimer dissociation. Cleavage of these areas induced the dissociation of the subunits along with destruction of the active centers and subsequently the loss of activity. It seems that the contact areas interact with active centers by conformational changes involving secondary structural elements.

The widespread antigenic changes lead to the emergence of a new type of coronavirus (CoV) called as severe acute respiratory syndrome (SARS)-CoV-2 that is immunologically different from the previous circulating species. Angiotensin-converting enzyme-2 (ACE-2) is one of the most important receptors on the cell membrane of the host cells (HCs) which its interaction with spike protein (SP) with a furin-cleavage site results in the SARS-CoV-2 invasion. Hence, in this review, we presented an overview on the interaction of ACE-2 and furin with SP. As several kinds of CoVs, from various genera, have at their S1/S2 binding site a preserved site, we further surveyed the role of furin cleavage site (FCS) on the life cycle of the CoV. Furthermore, we discussed that the small molecular inhibitors can limit the interaction of ACE-2 and furin with SP and can be used as potential therapeutic platforms to combat the spreading CoV epidemic. Finally, some ongoing challenges and future prospects for the development of potential drugs to promote targeting specific activities of the CoV were reviewed. In conclusion, this review may pave the way for providing useful information about different compounds involved in improving the effectiveness of CoV vaccine or drugs with minimum toxicity against human health.Communicated by Ramaswamy H. Sarma.

Nanoporous iron oxide (Fe 3 O 4 ) nanoparticles (NIONPs) have been widely used as promising agents in biomedical applications. Herein, the NIONPs were synthesized by one-step hydrothermal method and well-characterized by FESEM and TEM investigations. Afterwards, their interaction with human serum albumin (HSA) was studied using a wide range of biophysical approaches, including intrinsic and extrinsic fluorescence, far and near UV-CD, and UV-Vis spectroscopic methods as well as molecular docking investigation. Furthermore, the antibacterial effect of NIONPs was examined on the standard strains of the following pathogenic bacteria, Staphylococcus aureus (ATCC 25923), Klebsiella penumoniae (ATCC 33883), Enterococcus faecalis (ATCC 29212) and Pseudomonas aeruginosa (ATCC 27853). The results showed the feasible fabrication of spherical-shaped NIONPs with an average diameter of around 100   nm. Intrinsic fluorescence spectroscopy data depicted that NIONPs formed a complex with HSA by a K SV value of 0.092 (µg/ml) -1 . Extrinsic fluorescence, near UV-CD and UV-vis spectroscopic methods revealed that NIONPs induced some changes on the quaternary structure of HSA, whereas Tm measurement and far UV-CD spectroscopy showed some slight changes on the secondary structure of HSA even in the presence of high concentration of NIONPs. Molecular docking study disclosed that Fe 3 O 4 nanoclusters with varying morphologies and dimensions could interact with different residues on the surface of HSA molecules. In addition, antibacterial assays exhibited a significant inhibition on both Gram-positive and Gram-negative pathogenic bacteria. In conclusion, these NPs can be used as promising antibacterial agents.Communicated by Ramaswamy H. Sarma.

Nickel oxide nanoparticles (NiO NPs) have received great interests in medical and biotechnological applications. However, their adverse impacts against biological systems have not been well-explored. Herein, the influence of NiO NPs on structural changes, heme degradation and aggregation of hemoglobin (Hb) was evaluated by UV-visible (Vis) spectroscopy, circular dichroism (CD) spectroscopy, fluorescence spectroscopy, transmission electron microscopy (TEM), and molecular modeling investigations. Also, the morphological changes and expression of Bax/Bcl-2 mRNA in human lymphocyte cell exposed to NiO NPs were assayed by DAPI staining and quantitative real-time PCR (qPCR), respectively. The UV-Vis study depicted that NiO NPs resulted in the displacement of aromatic residues and heme groups and production of the pro-aggregatory species. Intrinsic and Thioflavin T (ThT) fluorescence studies revealed that NiO NPs resulted in heme degradation and amorphous aggregation of Hb, respectively, which the latter result was also confirmed by TEM study. Moreover, far UV-CD study depicted that NiO NPs lead to substantial secondary structural changes of Hb. Furthermore, near UV-CD displayed that NiO NPs cause quaternary conformational changes of Hb as well as heme displacement. Molecular modelling study also approved that NiO NPs resulted in structural alterations of Hb and heme deformation. Moreover, morphological and genotoxicity assays revealed that the DNA fragmentation and expression ratio of Bax/Bcl-2 mRNA increased in lymphocyte cells treated with NiO NPs for 24   hr. In conclusion, this study indicates that NiO NPs may affect the biological media and their applications should be limited.Communicated by Ramaswamy H. Sarma.

Studies on the anti-cancer effects of nanomaterials are a very important step in the clinical practice and treatment of cancerous tissues. Since IONPs have a high potential for cancer treatment, their anti-cancer properties can help us to resolve some of the therapeutic problems. For this purpose, in addition to synthesizing two types of IONPs including MN and MHN, Lf coating was used to increase their anti-cancer activity. MN and MHN were synthesized by hydrothermal and thermal methods, respectively, and their physicochemical properties were examined by SEM, zeta-potential, DLS, FTIR, TGA, and magnetism saturation. Molecular modelling was also done to model two steps of functionalization on the IONPs surface. In order to prove the biological activity of fabricated NPs in vitro, experimental assays of NP cytotoxicity were performed on breast cancerous cells (4T1) by MTT and ROS assays. It was found that the MN and MHN have a diameter around 24 and 33 nm, respectively. Also, the hydrodynamic radius of MN and MHN coated with Lf were 30 and 38 nm, and their zeta potential values at pH = 7.5 were -5.3 and -4.2 mV, respectively. Besides, the results of TGA, magnetism saturation and FTIR showed that Lf was successfully loaded onto NPs. Molecular modelling investigation depicted that dimethylamine moiety of the linker provides an intense reactive region for non-bonding linkages with Lf molecules. Cellular studies exhibited that Lf increased the toxicity of NPs and synthesized Lf-MNs provide the highest potency both on mortality and ROS level. This research may provide promising data for development of potential anticancer agents.Communicated by Ramaswamy H. Sarma.

Enzymes are one of the foundations and regulators for all major biological activities in living bodies. Hence, enormous efforts have been made for enhancing the efficiency of enzymes under different conditions. The use of nanomaterials as novel carriers for enzyme delivery and regulating the activities of enzymes has stimulated significant interests in the field of nano-biotechnology for biomedical applications. Since, all types of nanoparticles (NPs) offer large surface to volume ratios, the use of NPs as enzyme carriers affect the structure, performance, loading efficiency, and the reaction kinetics of enzymes. Hence, the immobilization of enzymes on nanomatrices can be used as a useful approach for direct delivery of therapeutic enzymes to the targeted sites. In other words, NPs can be used as advanced enzyme delivery nanocarriers. In this paper, we present an overview of different binding of enzymes to the nanomaterials as well as different types of nanomatrix supports for immobilization of enzymes. Afterwards, the enzyme immobilization on nanomaterials as a potential system for enzyme delivery has been discussed. Finally, the challenges associated with the enzyme delivery using nano matrices and their future perspective have been discussed.Communicated by Ramasamy H. Sarma.

This study is focused on the fabrication and characterization of titanium oxide (TiO 2 ) NPs. Afterwards; the interaction of TiO 2 NPs with human hemoglobin (Hb) was investigated by FTIR spectroscopy, fluorescence spectroscopy, and molecular docking studies. Also, the cytotoxic effect of fabricated TiO 2 NPs against human white blood cells (WBCs) was considered by MTT assay. The antibacterial effect of synthesized NPs was examined on Pseudomonas aeruginosa (ATCC 27853); Escherichia coli (ATCC 25922) and Staphylococcus aureus (ATCC 25923). TEM and DLS investigations showed that the synthesized TiO 2 NPs have a narrow nano-sized distribution. XRD pattern of the fabricated NPs exhibited that the TiO 2 NPs contain anatase phase. Similarity in amide I and II signal intensities showed that secondary structure of the adsorbed Hb is preserved. The intrinsic fluorescence study revealed that the fluorescence quenching of Hb was done by complex formation between Hb and TiO 2 NPs trough the hydrogen bond and van der Waals interactions. Synchronous fluorescence spectroscopy determined that interaction of TiO 2 NPs with Hb did not unfold the Hb structure in the vicinity of the Tyr and Trp residues. Molecular docking study depicted that Glu-95, Thr-134 and Tyr-140 are involved in the formation of hydrophilic bonds. MTT data and antibacterial assays indicated that TiO 2 NPs endow distinguished antibacterial activities against Gram-negative and Gram positive strains at safe concentrations. This study may reveal that fabricated TiO 2 NP can be used as a safe and potent antibacterial agent. Communicated by Ramaswamy H. Sarma.

Nanoparticles (NPs) due to their small size and high surface area induce remarkable adverse effects on the biological systems. However, the exact mechanism by which NPs interacted with biological system and induce their adverse effects is still an enigma. Herein, the interaction of zero valent iron NPs (ZVFe NPs) with human hemoglobin (Hb) was evaluated using a variety of techniques including circular dichroism, fluorescence, and UV-visible (UV-vis) spectroscopy methods. Also, the cytotoxicity of ZVFe NPs on the human lymphocyte cell line as a model of blood system cell line was investigated by reactive oxygen species (ROS), caspase-9, and caspase-3 activities assays. It was revealed that ZVFe NP interaction resulted in heme displacement and degradation and induction of protein cabonylation. It was also shown that ZVFe NPs impaired the complexity of lymphocyte cells through ROS generation and apoptotic pathway. Together, these data suggest that NPs influence the biological system and induce adverse effects through ROS generation.

Interestingly pharmaceutical sciences are using nanoparticles (NPs) to design and develop nanomaterials-based drugs. However, up to recently, it has not been well realized that NPs themselves may impose risks to the biological systems. In this study, the interaction of silver nanoparticles (AgNPs) with tau protein and SH-SY5Y neuroblastoma cell line, as potential nervous system models, was examined with a range of techniques including intrinsic fluorescence spectroscopy, circular dichroism (CD) spectroscopy, 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and acridine orange/ethidium bromide (AO/EB) dual staining method. Fluorescence study showed that AgNPs with a diameter of around 10-20 nm spontaneously form a static complex with tau protein via hydrogen bonds and van der Waals interactions. CD experiment revealed that AgNPs did not change the random coil structure of tau protein. Moreover, AgNPs showed to induce SH-SY5Y neuroblastoma cell mortality through fragmentation of DNA which is a key feature of apoptosis. In conclusion, AgNPs may induce slight changes on the tau protein structure. Also, the concentration of AgNPs is the main factor which influences their cytotoxicity. Since, all adverse effects of NPs are not well detected, so probably additional more specific testing would be needed.

The nanoparticle (NP)-induced conformational changes of protein and NP agglomeration have gained a remarkable interest in medical and biotechnological fields. Herein, the effect of human hemoglobin (Hb) on the colloidal stability of cerium oxide NP (CNP) was investigated by dynamic light scattering (DLS), zeta potential, and TEM analysis. In addition, the effect of CNP on the heme degradation and structural changes of Hb was studied using fluorescence, circular dichroism (CD), and UV-visible (UV-vis) spectroscopic methods. DLS and TEM analysis showed that the presence of Hb can increase the mean diameter of CNP. Zeta potential measurements revealed that CNP demonstrated a higher charge distribution relative to CNP/Hb complex. Besides, fluorescence studies indicated that two fluorescent heme degradation products are revealed during the interaction of CNP with Hb. Near UV-CD spectroscopy also showed that the microenvironmental changes of heme groups occur after interaction of Hb with CNP. The result of thermal behavior of Hb confirmed the structural changes of protein, which referred to decrease in the Hb stability in the presence of CNP. Indeed, the finding related to structural and functional changes of Hb induced by CNP may be crucial to obtain information regarding the side effects of NPs. Finally, this data reveal much insight into the effects of the interaction on protein structural changes and NP agglomeration, and can correlate the zeta potential of NP-protein complexes with the nature of the principle NP-protein interaction.

Nanoparticles (NPs) are one of the interesting and widely studying issues mainly because of their particular physico-chemical features and broad applications in the field of biomedical sciences, such as diagnosis and drug delivery. In this study, the interaction of iron nanoparticles (Fe-NPs) with Tau protein and PC12 cell, as potential nervous system models, was investigated with a range of techniques including dynamic light scattering, intrinsic fluorescence spectroscopy, circular dichroism, [(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium-bromid] assay, and acridine orange/ethidium bromide (AO/EB) dual staining method. An inverse correlation between Stern and Volmer constant (K SV ) and temperature indicated a probable static quenching mechanism occurred between Tau protein and Fe-NPs. The number of binding site (n = 0.86) showed that there is almost one binding site of Fe-NP per protein. The negative values of ∆H (-53.21 kJ/mol) and T∆S (-42.44 kJ/mol) revealed that Fe-NPs interacts with Tau protein with dominate role of hydrogen bonds and van der Waals interactions and this interaction was spontaneous (∆G = -10.77 kJ/mol). Also, Fe-NPs stabilized the random coil structure of Tau protein. Moreover, Fe-NPs reduced PC12 cells viability by fragmentation of DNA in an apoptotic manner. In conclusion, induced conformational changes of Tau protein and cytotoxicity of PC12 cells by Fe-NP were revealed to be in a concentration and time-dependent manner.

Herein, the interaction of iron nanoparticle (Fe-NP) with cytochrome c (Cyt c) was investigated, and a range of techniques such as dynamic light scattering (DLS), zeta potential measurements, static and synchronous fluorescence spectroscopy, near and far circular dichroism (CD) spectroscopy, and ultraviolet-visible (UV-vis) spectroscopy were used to analyze the interaction between Cyt c and Fe-NP. DLS and zeta potential measurements showed that the values of hydrodynamic radius and charge distribution of Fe-NP are 83.95 ± 3.7 nm and 4.5 ± .8 mV, respectively. The fluorescence spectroscopy results demonstrated that the binding of Fe-NP with Cyt c is mediated by hydrogen bonds and van der Waals interactions. Also Fe-NP induced conformational changes in Cyt c and reduced the melting temperature value of Cyt c from 79.18 to 71.33°C. CD experiments of interaction between Fe-NP and Cyt c revealed that the secondary structure of Cyt c with the dominant α-helix structures remained unchanged whereas the tertiary structure and heme position of Cyt c are subjected to remarkable changes. Absorption spectroscopy at 695 nm revealed that Fe-NP considerably disrupt the Fe…S(Met80) bond. In addition, the UV-vis experiment showed the peroxidase-like activity of Cyt c upon interaction with Fe-NP. Hence, the data indicate the Fe-NP results in unfolding of Cyt c and subsequent peroxidase-like activity of denatured species. It was concluded that a comprehensive study of the interaction of Fe-NP with biological system is a crucial step for their potential application as intracellular delivery carriers and medicinal agents.

In this study, a novel method to probe molecular interactions and binding of human hemoglobin (Hb) with nanodiamond (ND) was introduced based on the surface tension measurement. This method complements conventional techniques, which are basically done by zeta potential and dynamic light scattering (DLS) measurements, near and far circular dichroism (CD) spectroscopy, intrinsic and extrinsic fluorescence spectroscopy. Addition of ND to Hb solution increased the surface tension value of Hb-ND complex relative to those of Hb and ND molecules. The zeta potential values reveled that Hb and ND provide identical charge distribution at pH 7.5. DLS measurements demonstrated that Hb, ND, and ND-Hb complex have hydrodynamic radiuses of 98.37 ± 4.57, 122.07 ± 7.88 nm and 62.27 ± 3.70 at pH of 7.5 respectively. Far and near UV-CD results indicated the loss of α-helix structure and conformational changes of Hb, respectively. Intrinsic fluorescence data demonstrated that the fluorescence quenching of Hb by ND was the result of the static quenching. The hydrophobic interaction plays a pivotal role in the interaction of ND with Hb. Fluorescence intensity changes over time revealed conformational change of Hb continues after the mixing of the components (Hb-ND) till 15 min, which is indicative of the denaturation of the Hb relative to the protein control. Extrinsic fluorescence data showed a considerable enhancement of the ANS fluorescence intensity of Hb-ND system relative to the Hb till 60 nM of ND, likely persuaded by greater exposure of nonpolar residues of Hb hydrophobic pocket. The remarkable decrease in T m value of Hb in Hb-ND complex exhibits interaction of Hb with ND conducts to conformational changes of Hb. This study offers consequential discrimination into the interaction of ND with proteins, which may be of significance for further appeal of these nanoparticles in biotechnology prosecution.

Recently, the great interests in manufacturing and application of metal oxide nanoparticles in commercial and industrial products have led to focus on the potential impact of these particles on biomacromolecules. In the present study, the interaction of copper oxide (CuO) nanoparticles with bovine serum albumin (BSA) was studied by spectroscopic techniques. The zeta potential value for BSA and CuO nanoparticles with average diameter of around 50 nm at concentration of 10 μM in the deionized (DI) water were -5.8 and -22.5 mV, respectively. Circular dichroism studies did not show any changes in the content of secondary structure of the protein after CuO nanoparticles interaction. Fluorescence data revealed that the fluorescence quenching of BSA by CuO nanoparticles was the result of the formed complex of CuO nanoparticles - BSA. Binding constants and other thermodynamic parameters were determined at three different temperatures. The hydrogen bond interactions are the predominant intermolecular forces to stabilize the CuO nanoparticle - BSA complex. This study provides important insight into the interaction of CuO nanoparticles with proteins, which may be of importance for further application of these nanoparticles in biomedical applications.

Herein we have engineered a micellar Cu protoporphyrin catalyst that mediates carbon bond activation using peroxide as an electron source. Cu protoporphyrin is a biomimetic model of active site of chloroperoxidase enzyme, which catalyzes the carbon bond halogenation in the presence of a suitable amount of H 2 O 2 . The encapsulation of Cu(II) Protoporphyrin IX/L-Cysteine inside of cetyltrimethylammonium bromide micelle increases the rate of chlorination at pH 3. The cited catalyst resists high concentrations of hydrogen peroxide, which is previously reported as a suicide inactivator component of hemo-enzymes. Isothermal Titration Calorimetry (ITC) and Dynamic Light Scattering (DLS) data have revealed the formation of a micellar complex by encapsulation of six Cu(II) proporphyrins within each micelle. Moreover, electrochemical investigations indicate that L-Cysteine increases the intensity of electron transferred due to the formation of self-assembled monolayer on Au electrode. Our results paved a road toward the design of a more robust mimetic catalysis based on Protoporphyrin IX derivatives.