Monoterpenes, which have a unique diverse structure and are inexpensive, available and often enantiomerically pure, are an attractive renewable raw material for the development of physiologically active agents. One of the important methods to the utilization of monoterpenes is their interaction with carbonyl compounds resulting in heterocyclic compounds. Often these products exhibit analgesic, antiviral or neuroprotective properties. Earlier, we discovered anti-influenza A (H1N1) virus activity of several compounds with a hydro-2H-chromene scaffold, which were synthesized by the Prins reaction using p-menthane alcohols and carbonyl compounds; montmorillonite K10 or nanosized halloysite catalyst were used as the reaction catalysts [1]. Chromenols produced from an (–)-isopulegol and aliphatic ketones (acetone and cyclopentanone) demonstrated high activity in combination with low toxicity against the influenza virus [1].

The introduction of the fluorine atom into the molecule is an important strategy in the development of new biologically active compounds, which enables changing lipophilicity and electrostatic interactions and increasing the metabolic stability of compounds and, so affects their physiological activity. Here we synthesized fluoro- and hydroxy-containing octahydro-2H-chromenes by the Prins reaction starting from an (–)-isopulegol and a wide range of aromatic aldehydes in the presence of the BF₃∙Et₂O/H₂O system acting as both an acid catalyst and a fluorine source. Activity of the synthesized compounds against the influenza A/Puerto Rico/8/34 (H1N1) virus was studied. The highest activity was demonstrated by fluoro- and hydroxy-containing 2,4,6-trimethoxybenzaldehyde derivatives. These compounds were supposed to be capable of binding to viral hemagglutinin, which is an agreement with data on the effect of compounds on the viral fusogenic activity as well as with molecular docking studies.

[1] N.Salakhutdinov, K.Volcho, O.Yarovaya, Pure Appl. Chem., 2017;89:1105-1117.

In December 2019, a novel strain of coronavirus, SARS-CoV-2, was identified. Infected patients revealed symptoms of fever, cough (dry), sore throat, and fatigue, which began manifesting after 5 days of incubation. Hoping to prevent transmission, many countries adopted a mandatory mask use in closed public spaces. However, most mask options display a passive action against COVID-19. To overcome such restrictions, this work proposes the incorporation of anti-viral essential oils (EOs) loaded onto a nanofibrous layer that can be adapted to both community and commercial masks.

Twenty EOs selected based on their antimicrobial nature were examined for the first time against the Escherichia virus MS2. The most effective were the lemongrass (LO), Niaouli (NO) and eucalyptus (ELO) with a minimum inhibitory concentration (MIC) of 356.0 mg/mL, 365.2 mg/mL and 586.0 mg/mL, respectively. Polycaprolactone (PCL) and cellulose acetate (CA) were prepared individually at 14 wt% in chloroform/dimethylformamide (DMF) and 10 wt% in acetone/DMF, respectively, and combined at 3:1 ratio. Polymeric solutions were then processed via eletrospinning with processing parameters being optimized to 24.7 kV, 3.2 mL/h and 21 cm. Uniform, beadless nanofibers were obtained. Mats were characterized as mechanically resilient, to endure movements arising from mask positioning, and hydrophobic in nature, to repel droplets coming from the exterior. Loading of the nanofibrous mats was accomplished via physisorption using the free -OH groups of the CA as linkers. Mats were loaded with the EOs at MIC concentration for 72 h (saturation). Presence of the EOs was confirmed along the mats. Antimicrobial testing via halo determination, verified their diffusion abilities. More importantly, time-kill kinetics testing of the loaded mats attested to the EOs capability to fight the virus MS2 even when bonded to the nanofibers. Data demonstrated the potential of these EOs-loade

The high mortality rate of different multi-resistant bacteria (MDR) has led to an immediate and urgent solution. Patients hospitalized for chronic diseases have a weakened immune system and are at high risk of contracting an opportunistic infection. Likewise, WHO prioritized studies against a selected group of MDR bacteria for their control [1]. In this scope, the Ctx(Ile²¹)-Ha antimicrobial peptide (AMP) presented great potential and efficient biological activity against Acinetobacter baumannii and Pseudomonas aureginosa MDR bacteria [2]. Thus, the aim of this research was to design ultrasound-assisted microstructured films loaded with the Ctx(Ile²¹)-Ha AMP, based on starch and chitosan, for its effective protective action. Gelling was done, for grain breaking and exposing the hydroxyls [3]. For this, it was used 10 g cornstarch and 300 mL distilled water under agitation at 90°C for 1 h. Then, added 5 mL of the gelled starch and mixed with 50 mg of peptide and stored in petri dishes, at 50°C for 5 h. Chitosan film was synthesizing by free radical polymerization in the presence of crosslinker [4]. Chitosan dispersion (CD) was prepared by dissolving 2% w/v chitosan in 2% v/v acetic acid solution. Ctx(Ile²¹)-Ha was placed on the CD with 0.3% w/v of glycerol and magnetic agitation at 150 rpm. For this, its properties were evaluated by DSC/TGA, FTIR, XRD and SEM. The physicochemical stability studies of the AMP showed its structure unchanged for up to 3 months exposed to water and for up to one year in the form of a dry film. These results were confirmed by the LC/MS profile, in which XDR indicate a consistent semi-morpho phase. Finally, with these results, we show that new products based on AMPs could be potential anti-MDR bacterial agents, avoiding the exposure of critically ill patients in intensive care or post-surgery beds and preventing their dissemination.

The virus is a microorganism that uses the machinery of the host to multiply. At present, there are various species of viruses known to us that are dangerous for the health of human beings. One of such viruses has destroyed many lives nowadays and that is a coronavirus. Such other viruses like Human Immunodeficiency Virus, Poliovirus, etc. destroy one’s capability to survive normally. As science progresses, we invent many antiviral drugs as per the type of virus. There are many antiviral drugs available to treat viral infections. From them, benzothiazole derivatives are potent antiviral agents. Researchers continuously work on benzothiazole moiety to get more effective benzothiazole derivatives that can be used as antiviral agents. This review article gives information about various benzothiazole derivatives that act against the various viruses as antiviral agents, the structure-activity relationship of benzothiazole as an antiviral agent, various schemes to synthesize benzothiazole derivatives as an antiviral agent as well as includes various methods to evaluate the antiviral activity of novel synthetic compounds against specific viruses.

Under the influence of many factors, such as cytokines or chemokines, macrophages specialize into two subpopulations: pro-inflammatory M1 (classical pathway) or anti-inflammatory M2 macrophages (alternative pathway). TLR (toll-like receptors) 1/2 receptors upon stimulation with the bacterial ligand PAM3CSK4 and TLR4 upon stimulation with LPS, activate the NFκB pathway, which leads to the down-regulation of catalase expression, through the activity of LSD1 and HDAC1 complex. The main factor responsible for CAT repression is the recruitment of LSD1 and HDAC1 to the promoter site of the gene, resulting in pausing of RNA polymerase. Inhibition of LSD1 with SP2509 leads to decreased expression of cytokines such as IL1b and COX2, as well as some surface proteins e.g. TLR2, despite the presence of LPS. iLSD1 prevents the catalase repression and, thereby, leads to inhibition of macrophage polarization into the classic pro-inflammatory M1 phenotype. In conclusion, regulation of catalase expression determines the direction of macrophage specialization.

Throughout history, natural products have played a major role in the discovery of drugs, especially cancer and infectious diseases. Natural products and their similarity and historical composition have contributed greatly to the healing of medicine. However, natural products have their own drug discovery challenges, such as technical barriers to testing, classification, performance, and efficiency, leading to a reduction in their research by the pharmaceutical industry. In recent years, many technological and scientific advances, including improved analytical tools, genetic engineering, engineering techniques, and the development of microbial farming, are facing these challenges and opening up new opportunities. Here, we summarize the latest technological advances that enable the availability of drugs for natural products, highlight selected applications and discuss key opportunities. Recent advances in genomics and structural biology over the past few decades paint a vivid picture of protein variations targeted at natural product molecules. Apart from this, current leadership strategies have led to a renewed interest in natural products in drug discovery. As a result, interest in natural products such as drug lead is rekindled, especially in dealing with antimicrobial resistance. We continue to attract readers' interest in acknowledging that a certain number of natural products/products are actually produced by bacteria and/or bacterial interactions with the "host where they have been set aside"; therefore, we consider this area of ​​natural product research should be greatly expanded. In the concluding section, we draw attention to the potential future indications of a natural product in drug design and development.

Chronic wounds (CW) create numerous entry ways for pathogen invasion and prosperity, further damaging host tissue and hindering tissue remodelling and repair. Essential oils (EOs) exert quick and efficient antimicrobial (AM) action, unlikely to induce bacterial resistance. Cinnamon leaf and clove oils (CLO and CO) exert strong AM activity, namely against Staphylococcus aureus and Pseudomonas aeruginosa. Chitosan (CS) is a natural and biodegradable cationic polysaccharide, also widely known for its AM features. CS and poly (vinyl alcohol) (PVA) films were prepared (ratio 30/70; 9%wt) by solvent casting and phase inversion method. Film’s thermal stability and chemical composition data reinforced polymer blending and EO entrapment. Films were supplemented with 1 and 10wt% of EO in relation to total polymeric mass. Film’s thickness and degree of swelling (DS) tended to increase with EO loading amount, particularly with 10wt% CLO (*p<0.05). AM testing (agar diffusion assay and time-kill kinetics) revealed that CS films alone were effective against both bacteria, and capable of eradicating all P. aeruginosa within the hour (***p<0.001). Still, loaded CS/PVA films showed significantly improved AM traits in relation to unloaded films right after 2h of contact. This study is a first proof of concept that CLO and CO can be dispersed into CS/PVA films and show bactericidal effects, particularly against S. aureus, this way paving the way for efficient CW therapeutics.

Linearolactone (LL) isolated from Salvia polystachya presents antiparasitic activity against E. histolytica and G. lamblia through ROS production, an apoptosis-like process, and alteration of the actin cytoskeleton. However, the possible toxicological effects or molecular mechanisms of LL are still not understood. The aim of this study was to determine the pharmacological and toxicological properties of LL by bioinformatic analyzes. The pharmacological activities, toxicological risks, and molecular targets of LL were determinate by free software such as Molsoft©, Molinspiration©, ToxiM©, SuperCYPsPred©, and SEA©. Molecular docking with key proteins for the pathogenic activity of Entamoeba histolytica trophozoites, such as myosin-II and calreticulin, was performed with AutoDock-Vina and UCSF-Chimera. Results revealed that LL present drug-likeness of -0.55 and ToxiM of 0.958 due to medium toxicity associated with interactions in nuclear receptors (0.66), GPCR ligands (0.65), and enzymatic inhibitions (0.47) related to the cytochrome-P450 system (CYP3A4, low). Results indicate that LL is a hydrophobic molecule (LogP: 1.59) with intermediate intestinal absorption (TPSA: 65.75, CACO-2 permeability) and medium blood-brain barrier penetration (3.86). SEA analysis demonstrated that the potential target pharmacophores are OPRK1 (P-Value: 6.49 x10-37, Max TC: 0.49) and Nlrp3 (P-Value: 3.90 x10-19, Max TC: 0.36) in humans. Molecular docking of LL with E. histolytica proteins showed high affinity to ATP-binding catalytic site in heavy-chain (GLU-187.A, THR-186.A, ASN-234.B) of myosin-II (-8.30 Kcal/mol), as well as in the chain-A and C (LYS-199.A, LYS-152.C) of calreticulin (-8.77 Kcal/mol). As conclusions, LL is a compound with possible moderate toxicity, sedative effects on CNS, and anti-inflammatory properties. In addition, LL probably inhibits amoebic liver abscess formation through interactions with myosin-II and calreticulin from E. histolytica, but in-depth studies are necessary to confirm these claims.

Tuberculosis is a global health burden especially in tropical contries. Extensive increaments in MDR and XDR tuberculosis points out ineffectiveness of established anti-Tb agents. There is urgent necessity to find our potent anti-Tb agents with unique mechanisms. Green tea and Black tea polypgenols have great potential to inhibit viruses including SARS-COV-2, bacterial strains, etc. In this context, we have screened and elucidated 30 Green tea and black tea polyphenols against mycobacterial pantothenate synthetase and enoyl acyl carrier enzymes. Our molecular docking results revealed that Epigallocatechin gallete had higher binding affinity against 2X22 and 3IVX targets with docking scores of -185 and -190 Kcal/mol. Furthermore, our molecular docking simulation for 10 ns resulted better stability of these complexes. We have also evaluated in-silico drug-likeness and toxicity profiles for studies polyphenols. Our in-silico toxicity analysia suggested that these polyphenols would exhibit lesser toxicity like eye corrosion, skin irritations, etc.Thus, our present study would provide better insights for studying naturally occuring polyphenols as potential anti-Tb agents.

The devastating nature of the SARS-CoV-2 pandemic has fostered the need for potent therapeutics to manage or curb its severity. As a response, several studies on drug repurposing, vaccine design and optimizing natural phytochemicals are ongoing. This study aims at screening for potent and novel anti-COVID phytochemicals from the rhizome of Curcuma longa. A phytochemical library of 50 non-ubiquitous bioactive compounds from the rhizome of Curcuma longa was retrieved from Dr. Duke's phytochemical and ethnobotanical database (https://phytochem.nal.usda.gov/phytochem/search). The compounds in the library were docked against the receptor binding domain (RBD) of SARS-CoV-2 (PDB ID: 7EAM_1). Three compounds - Quercetin; 1,7-Bis-(4-hydroxyphenyl)-1-heptene-3,5-dione; and Cyclocurcumin, were selected based on their higher docking score than the standard repurposed drug (Arbidol). This study further examined the interactions of the novel 1,7-Bis-(4-hydroxyphenyl)-1-heptene-3,5-dione (BHHD) in the binding pocket as well as its ADMET properties. Excellent interaction was observed between the atoms of BHHD and amino acid residues known to foster the viral entry into the host. Furthermore, the ADMET result for BHHD was impressive for a lead molecule. Therefore, this study recommends for further investigation on the potency and toxicity of BHHD both on cell lines and animal models.