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a & b -Structure of Hydroxychloroquine (HCQ) and Hyaluronic acid -Hydroxychloroquine Conjugate (HA-HCQ).
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In-silico anti-viral activity of Hydroxychloroquine (HCQ) and its Hyaluronic Acid-derivative (HA-HCQ) towards different SARS-CoV-2 protein molecular targets were studied. Four different SARS-CoV-2 proteins molecular target i.e., three different main proteases and one helicase were chosen for In-silico anti-viral analysis. The HA-HCQ conjugates exhi...
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... 2D structure of Hydroxychloroquine (HCQ) and Hyaluronic Acid-Hydroxychloroquine Conjugate (HA-HCQ) are drawn in ACDChemsketch and saved as mol format file ( Fig. 1 a & b) [22] . The retrieved 2D SDF file format of HCQ and HA-HCQ conjugate structure was submitted to "Online SMILES convertor and Structure file generator", and converted into 3D PDB format [23] . ...
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The main protease, M pro , of SARS-CoV-2 is an essential viral protein required for the earliest steps of infection. It is therefore an attractive target for antiviral drug development.
Citations
... By conjugating MTX with HA, the researchers aimed to enhance drug delivery, potentially improving the treatment outcomes and reducing adverse effects associated with conventional MTX formulations. This research demonstrates the valuable application of HAbased conjugates in expanding the therapeutic options for anticancer drugs like MTX, potentially offering more effective and targeted treatments for liver metastasis and mammary carcinoma [157]. Toxicology and pharmacokinetics analyses have displayed an extended half-life and amplified area under the curve (AUC) worth concerning free MTX [158]. ...
... To mitigate its intrinsic toxicity, enhance its bioavailability, localization, and controlled release, and improve its efficacy, a proposal has been developed to conjugate it with HA to formulate a hyaluronic acid-hydroxychloroquine conjugate [156]. The ability of hyaluronic acid to form conjugates with pharmacologically active compounds offers an opportunity for this approach [157]. However, no clinically approved immunoglobulins or specific therapeutic drugs are available for COVID-19. ...
Hyaluronic acid (HA) has a broad range of cosmetic and therapeutic applications due to its unique physicochemical properties and involvement in various essential biological processes, including cell signaling, wound reparation, and tissue regeneration. In this review, we provide a comprehensive overview of HA, including its history, physicochemical properties, roles, molecular biology, and biochemistry (including occurrence, biosynthesis, and degradation), as well as its chemical modifications and conventional and emerging production methods. We also examine HA’s medical, pharmaceutical, and cosmetic applications and its derivatives in arthrology, ophthalmology, wound healing, odontology, oncology, drug delivery, 3D bioprinting, and cosmetology. Finally, we discuss the potential role of HA in preventing Covid-19. Hyaluronic acid, a naturally found substance, has shown immense potential in the clinic. Thus, it is imperative
to highlight its applications in the diverse fields impacting the lives of patients and healthy individuals.
... The in silico testing of a hyaluronan-hydroxychloroquine conjugate and a hyaluronic acid derivative was carried out to assess the antiviral activity toward different SARS-CoV-2 proteases and helicase targets. Superior binding affinity and interactions with the majority of the screened SARS-CoV-2 molecular target proteins were reported for the hyaluronan-hydroxychloroquine conjugate ( Table 2) [81]. ...
Infection with the novel coronavirus SARS-CoV-2, the cause of coronavirus disease (COVID-19), has emerged as a global pandemic, with a high toll on casualties, economic impact, and human lifestyle. Despite the recent approval of various vaccines against the virus, challenges remain, including the limited availability of these vaccines, the prevalent rejection of vaccination by a large proportion of the population, and the recurrent appearance of new variants of the virus due to mutations. This context raises the alarm for scientists and clinicians to seek alternative and complementary therapies. In this context, natural products and their derivatives serve as reservoirs for potential therapeutic compounds that can be exploited in the research and production of antiviral drugs against COVID-19. Among these substances, lectin and polysaccharides isolated from fauna and flora emerge as complementary strategies for treating coronavirus infection. The review objective is to cover and analyze the specific role of polysaccharides and lectins and their synergy in the fight against this deadly SARS-CoV-2 virus. For this purpose, a primary literature search was conducted on Google Scholar, PubMed, and Web of Sciences using relevant keywords like “SARS-CoV-2 Variants”; “Antiviral Strategies”; “Antiviral Polysaccharides”; “Antiviral Lectins”; and “Synergistic effect”. The results demonstrate that lectins and polysaccharides exhibit antiviral activities against SARS-CoV-2 via mechanisms related to binding and steric blocking, the binding of glycan-based decoys, chemical reactions, virus particle disruption strategies, and steric blocking for competitive inhibition to block SARS-CoV-2 and its variants’ entry. In addition, this review analyzes the rationale behind combining polysaccharides and lectins, emphasizing complementary mechanisms of action. By simultaneously targeting multiple stages of the viral life cycle, this dual strategy aims to comprehensively inhibit viral propagation and enhance the durability of antiviral strategies over time.
... In silico study showed high binding energies of our tested agents, especially sars-coV-2. the composite blocked viral host receptor ace2 [ 50 ] cs/α-ag 2 [ 61 ] Ha-Hydroxychloroquine (Ha-HcQ) --Ha-HcQ conjugates showed superior binding affinity and interactions with all the screened sar-coV-2 molecular target proteins with the exception of a few targets [ 62 ] Ha-loaded niosomes red blood cells rats (male sprague dawley drug release studies from the Ha-loaded niosomes showed a controlled release profile, and in vivo studies revealed Ha greater localization in lung than in other tissue [ 63 ] Ha-Gse4 peptide-Poly (ethylene glycol) ...
... HA also forms a unique viscous network (viscoelastic properties) [106,107] that makes it an excellent candidate for biomedical applications [108]. For example, Thirumalaisamy and co-workers evaluated the in silico antiviral activity of hydrochloroquine (HCQ), a conventional anti-malarial drug with antiviral activity against SARS-CoV-2, and its hyaluronic acid conjugate (HA-HCQ) towards different SARS-CoV-2 protein molecular targets [109]. The HA-HCQ derivative corresponded to HCQ covalently linked through an ester linkage to HA in a specific position (i.e., C5 carboxylic group of the glucuronic moiety) in order to have an increased bioavailability, safety or controlled released in the body, together with the reduction in its systemic toxicity. ...
... The HA-HCQ conjugate also showed maximal drug delivery to the respiratory tract with increased drug clearance and less toxicity to host cells. Of course, in vitro and in vivo studies are still needed to confirm not only the drug delivery safety and targeting receptors, but also the toxicity, solubility and efficacy of HA-HCQ conjugates [109]. ...
... In Table 3, there is a short summary of the reported and explored polymer-based strategies for use in the treatment of both SARS-CoV-2 and influenza A. Table 3. Polymer-based strategies applied in the possible treatment of SARS-CoV-2 and influenza A viruses. In silico [109] Loaded NPs SARS-CoV-2 Synthetic (PLGA-PEG-Mal) At 4 h treatment, the IVM-NP was able to decrease the expression of viral spike protein and its receptor angiotensin-converting enzyme 2. ...
Towards the end of 2019 in Wuhan, suspicions of a new dangerous virus circulating in the air began to arise. It was the start of the world pandemic coronavirus disease 2019 (COVID-19). Since then, considerable research data and review papers about this virus have been published. Hundreds of researchers have shared their work in order to achieve a better comprehension of this disease, all with the common goal of overcoming this pandemic. The coronavirus is structurally similar to influenza A. Both are RNA viruses and normally associated with comparable infection symptoms. In this review, different case studies targeting polymeric materials were appraised to highlight them as an indispensable tool to fight these RNA viruses. In particular, the main focus was how polymeric materials, and their versatile features could be applied in different stages of viral disease, i.e., in protection, detection and treatment.
... However, the degree of substitution is poor, generally below 20%. This is preferable to most biological investigations so as not to interfere with CD44 interaction [76][77][78][79]. Following chemical conjugation, various crosslinking methods can be employed to allow for use in multiple applications, from tissue engineering to wound healing and aesthetics. ...
The inclusion of physiologically active molecules into a naturally occurring polymer matrix can improve the degradation, absorption, and release profile of the drug, thus boosting the therapeutic impact and potentially even reducing the frequency of administration. The human body produces significant amounts of polysaccharide hyaluronic acid, which boasts exceptional biocompatibility, biodegradability, and one-of-a-kind physicochemical features. In this review, we will examine the clinical trials currently utilizing hyaluronic acid and address the bright future of this versatile polymer, as well as summarize the numerous applications of hyaluronic acid in drug delivery and immunomodulation.
... Therefore, the binding affinities of the chosen natural phenolic compounds were determined by analyzing binding conformations and interactions of each compound with the active site of the receptor. Considering the previous in silico studies reported in the literature, it is obvious that some amino acid residues such as Gln19, Thr24, Thr25, Thr26, Leu27, His41, Ser46, Met49, Asn119, Asn142, Gly143, His164, Met165, Glu166, Asp187, Arg188, and Gln189, might play a strong role in the inhibitory activity (Rajagopal et al., 2021;Thirumalaisamy et al., 2021). ...
Coronavirus (SARS-CoV-2) causes a new type of severe acute respiratory syndrome that first appeared in Wuhan in December 2019; it is a very fast-spreading and deadly virus. Therefore, urgent discovery or development of “lead compounds” against this virus is crucial. Natural compounds have always served as a great source, especially the use of traditional medicinal plants, in modern drug discovery. This study aimed to investigate the SARS-CoV-2 protease inhibition potential of the phenolic compounds in the genus Satureja L. The affinities of the chosen natural products were understood using molecular docking simulation against the SARS-CoV-2 protease enzyme. The study proved that three different phenolic compounds namely 5,6-dihydroxy-2-(4-hydroxy-3-methoxyphenyl)-7,8-dimethoxy-4H-chromen-4-one, 2-(3,4-dimethoxyphenyl)-5,6-dihydroxy-7,8-dimethoxy-4H-chromen-4-one, and 5,6-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-7,8-dimethoxy-4H-chromen-4-one obtained from Satureja L. taxa were found as promising against SARS-CoV-2 main protease.
... It is quite interesting to mention that our previous research study [31] results revealed that HA-HCQ conjugate shown more bioavailability, less toxicity and ease of clearance from the body when compared to its free form of drug HCQ. It is worth mentioning here that conjugation of drugs with hyaluronic acid enhances the pharmacokinetic profiles of the drugs themselves. ...
... We confirm that HA-HCQ drug conjugate will be useful to establish a promising early stage antiviral drug for the novel treatment of COVID-19. [31]. ...
We propose a novel and efficient drug for COVID-19 disease
With the widespread application of mixed-mode chromatography in separation analysis, it is becoming increasingly important to study its retention mechanism. The retention behavior of acidic compounds on mixed-mode octyl-quaternary ammonium (Sil-C8-QA) columns was investigated by computer simulation. Firstly, the benzoic acid homologues were used as the analytes, and the simulation model was constructed by the Materials Studio. Geometric optimization, annealing and molecular dynamics (MD) simulation of these complexes resulted in optimized conformations. The binding energy, mean square displacement (MSD) and torsion angle distribution generated by MD simulation were then analyzed. The results showed that the more negative binding energy, the greater the MSD and the narrower the torsion angle distribution, indicating that the stationary phase behaves with stronger interaction and retention. The retention behavior of five acidic drugs on the Sil-C8-QA column was then successfully explained by simulation. Acidic drugs are more retentive on the mixed-mode column due to the more substantial interaction brought by the reversed-phase/ion-exchange mixed-mode mechanism compared to other single-mode columns. This simulation method is expected to provide ideas for studying the separation mechanism and predicting the retention behavior of more complex samples.
