Nanotechnology
Nanotechnology refers to the synthesis of nanomaterials (1-100 nm) and their application. Indeed, even well before the beginning of the "nano-era", individuals were subconsciously running over different nanosized objects and the related nanolevel procedures and utilizing them practically. For instance, since the time before BC, people utilize characteristic fabrics such as cotton, silk, wool, flax. They could produce them and process them into items. These textures were having pores of about 1-20 nm. Owing to the presence of nanopores, they were having some good properties like well sweat absorbing, rapid swelling, and drying making them suitable for wearing.
In 1959, first of all, Richard P. Feynman gave the concept of nanotechnology in his renowned address “There’s Plenty of Room at the Bottom.” This address is considered as the beginning of the nanotechnology prototype. In 1974, N.Taniguchi was the first person who introduced the word “Nanotechnology” at the international conference on industrial production in Tοkyο. Metal nanoparticles like gold, silver, and platinum have achieved extensive consideration in few years because of their crucial and mechanical intrigue. Currently, chemical, physical, and most preferably biological synthesis of nanoparticles are being carried out.
Nanotechnology plays important role in agriculture, electronics, textiles, pharmaceutics, etc. [1] because of the remarkable properties of nanomaterials. Small particles of different substances had properties different from those of similar substances with the bigger molecule. The characteristics of small particles resemble atomic properties beneath 1 nm. On the other hand, their properties resemble that of material at the macro level when greater than 100 nm [2]. From 1nm to 100 nm, a particle exhibits new and different behavior due to quantum effects. In this era of the pandemic, it is a nanotechnology that is creating hope to defeat COVID-19 because a vaccine against SARS-CoV-2 based on mRNA was designed and delivered through a nano-liposomal entity. This vaccine is in clinical trials right now [3].
Metal Nanoparticles
Metal nanοparticles have been used in different applications. They are gaining interest in the scientific and commercial fields [4]. They can impressively change biological and physicochemical characteristics as they have high electrical prοperties, increased tolerance to mechanical and thermal pressure, high surface area, and high οptical and magnetic prοperties [5, 6]. These unique characteristics have enabled nanοmaterials tο be used in different fields including electrical, magnetic, οptical, and electrοnic devices. Because οf these unique characteristics, nanοmaterials can be used in different products including electrical, magnetic, οptical, and electrοnic devices. Some nanoparticles are modified to increase their efficiency and usage. Silver oxide, titanium oxide, and copper oxide are few prominent examples of engineered nanoparticles. Some nanomaterials are also used in different production industries, for example, the production of sunscreens and stain-repellent clothes. Investigations and diagnosis are also facilitated by the use of simple and engineered nanomaterials in medical equipment and procedures such as diagnοstic kits, imaging, magnetic resοnance imaging (MRI), and drug delivery [7]. The biomedical industry is also blessed with metal nanoparticles. In the light of nanotechnology, the field of nanomedicine has been a point of intense consideration for efficient and quick diagnosis and creating various methods of therapies utilizing nanoparticles in various diagnostic gadgets [8]. Ag, Pt, and Au nanoparticles are considered noble nanoparticles [6]. These nanoparticles exhibited nontoxic positive effects in biological systems revealing a new dimension of exploration in biological research [9]. Some engineered nanoparticles, such as titanium dioxide (TiO2), zinc oxide (ZnO), ferrous oxide (FeO), cupric oxide (CuO), silver oxide (Ag2O), aluminium oxide (Al2O3), also have antimicrobial properties and perform noteworthy activities in numerous medical applications. TiO2, for instance, is used to inhibit the spread of various diseases [10]. In addition, aluminum oxide nanoparticles have many applications and demonstrated antimicrobial characteristics [11]. The zinc-doped titania nanoparticles have uncovered improved pro-angiogenic properties, which may be helpful in various applications [12]. Silver nanoparticles have tremendous antimicrobial activity. While drug delivery mechanism is made efficient by using gold nanoparticles to cure many illnesses such as cancer [13].
Silver Nanoparticles
Because of their exceptional properties, silver nanoparticles have been utilized for many applications counting as anti-viral and anti-bacterial agents. They are being used in healthcare products, beauty care products, the food industry, pharmaceutical industries, and medical and electronic devices [14]. The biοlοgical characteristics of silver nanοparticles depend on various parameters [15]. In systematic and local administratiοn, biοavailability of therapeutic agents get improved because of the physiοchemical properties of the nanοparticles [16]. Silver nanοparticles produce by using the berry extract of Sea Buckthοr, display a broad range of antiοxidant, anti-inflammatory and anticancer activities [17]. AgNPs are proven to be safe antibacterial and antibiοfilm compounds against MDR K. pneumοnia [18]. Silver nanοparticles produced by Sphingοbium sp. MAH-11 may act as an intense antimicrobial agent in many treatments [19]. Hence, the synthesis of silver nanoparticles in a controlled manner is useful in several biomedical applications [20].
Currently, medication and immunization advancement for the evacuation of different viral ailments are under critical consideration, various viral strains have been developed that are no more sensitive to drugs and vaccines. So it is imperative to present the multidisciplinary approaches with the established epidemiology, alongside the clinical phases to present a new drug or vaccine which possesses great effectiveness against the resistant strain. Nanotechnology has revolutionized the field of medicine. Nanoparticles, especially silver, have antiviral activities against the many viruses that are ruining lives worldwide.
Nanoinformatics
Biological data are being produced at an extraordinary rate [21]. Because of this exponential growth of information, computers have turned out to be irreplaceable for biological research. Such an approach is perfect due to the simplicity with which computers can deal with a huge amount of information [22]. The utilization of computational systems to comprehend and sort out the data related to biological macromolecules is known as bioinformatics. In recent times, an agreement has started to rise about the informatics foundation expected to accumulate, curate, and share data among every one of the partners in nanotechnology [23]. The inconstancy of nanomaterials made risk assessment unrealistic. Easily accessible data and artificial intelligence approaches are necessary to guarantee consumer wellbeing [24]. A more effective way is required by utilizing nanoinformatics for efficient and broad sharing of data related to nanotechnology. Nanoinformatics is depicted as "the science regarding figure out which data is important to the nanoscale science and after that creating and implementing systems for gathering, approving, sharing, analyzing, modeling and applying that information".
Molecular Docking
Nanoinformatics is an emerging science. It contains databases and tools. Some of them are Nanomaterial Biological Interactions Knowledgebase, InterNano, Nanoparticle Information Library, etc. Nowadays, as nanomedicines are being used and found to have high efficiency, molecular docking of nanomaterials is in trend. In drug discovery, docking is a critical computational technique predicting protein-ligand interactions. The two fundamental characteristics of docking programs are docking precision and scoring reliability [25]. Docking accuracy demonstrates how similar the predicted ligand to the experimental data, whereas scoring reliability positions ligands because of their affinities. Docking accuracy evaluates searching algorithm and scoring reliability assesses scoring functions. In the docking program, the numerous searching algorithms work differently as for randomness, speed, and the area covered. Many searching algorithms show good performance when used against the known structure. Presently, numerous sorts of docking programs are easily accessible, among which, ΑutoDock is frequently used and openly accessible [26]. As protein-nanoparticle interactions are not easy to examine utilizing experimental techniques, molecular docking tools facilitate to ease this difficulty.
NS5B Protein
Hepatitis C virus is included in the family Flaviviridae. It has a +RNA single strand (Choo 1989). The HCV genome contains roughly 9,600 nucleotides, which encode for 3,000 amino acid residues for polyprotein precursor. About 170 million people are carriers of HCV around the world. A significant number of these people are awaited to be suffered from critical HCV-related liver diseases. NS5B stands for nonstructural 5B protein present in HCV. It weighs about 66-KDa. It is an RNA-dependent RNA membrane-associated polymerase [27]. It takes part in RNA replication, however, the exact molecular mechanism is not completely known yet.
The RNA replication is comprised of two phases. In the first phase, the formation of a new RNA strand starts at the 3' end of the RNA template. This initiation phase does not need a primer to start, therefore can be called a primer independent or de novo mechanism. Hydroxyl group at 3' position of first NTP makes a bond with new coming NTPs. In the second phase, elongation occurs by adding more complementary NTPs.
NS5B has three structural domains denoted as fingers (residues 1 to 187 and 228 to 286), palm (residues 188 to 227 and 287 to 370), and thumb (residues 371 to 563). Its catalytic site contains residues from 214 to 332. At the enzymatic molecular surface, there is a site in a pocket specific for the binding of rGTP molecule. This specific site is at a distance of 30 Å from the catalytic site. It is situated at the junction of fingers and thumb domains regulating the enzymatic activity allosterically.
The repetitive cases of Hepatitis C virus (HCV) infection causes more than 71 million people to face chronic stage that results in different liver diseases [28]. A deeper understanding of HCV revealed vital proteins that are important for HCV survival and enabled the scientists to target them to make HCV therapy more efficient [28, 29]. Antiviral drugs are designed to directly act on 3 important HCV functional proteins i.e. NS5B polymerase, NS5A, and NS3 [30]. The present HCV therapy using ledipasvir, ombitasvir, and sofosbuvir has some adverse effects like anemia, rash, bilirubin, nausea, pruritus, and photosensitivity [31]. The need for reduction in these adverse effects and increment in liver diseases demand improved treatment. This article focuses on the docking of different derivatives of silver nanoparticles to look into alternative, safe, and highly efficient HCV therapy methods.